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The Child With Food Allergy
Pediatricians play an integral role in the initial diagnosis and management of children with a suspected food allergy. History, some useful laboratory tests, and careful counseling can go a long way to identify these sometimes challenging patients.
A considerable amount of anxiety often surrounds food allergy concerns, and this should be addressed (or at least acknowledged) with patients and their families.
Start with history, the most important diagnostic factor: Ask children and parents about specific symptoms, their timing, and foods the child has ingested. If the child experienced anaphylaxis, then include medication and insect stings in your history taking. The good news for primary care is that 90% of food allergies are caused by a few foods: milk, egg, wheat, soy, peanut, fish, shellfish, and nuts. Other triggers are relatively rare.
Allergy skin testing and/or specific immunoglobulin E (IgE) blood tests can support your diagnosis. However, these findings need to be correlated with history because false-positive results occur frequently. It is important to realize that the level of specific IgE to a food is not correlated with the severity of a reaction, but instead is correlated with the likelihood of having a single reaction.
Determine if the child's symptoms truly suggest an allergic reaction or instead point to a non–food-related cause. Psychological conditions such bulimia, anorexia, or factitious disorder can mimic a food allergy, for example.
Your differential diagnosis also includes structural abnormalities of the GI tract; cystic fibrosis with chronic diarrhea from pancreatic insufficiency; and illness caused by contaminants and additives such as flavorings, dyes, preservatives, or infectious organisms. Also check for exposure to pharmacologic contaminants such as caffeine or tyramine in certain foods.
Rule out lactose intolerance and other disaccharidase deficiencies (especially if the symptoms are limited to the GI tract) and a non-IgE reaction called food protein-induced enterocolitis syndrome (FPIES). An FPIES diagnosis is based on clinical presentation and symptoms because allergy skin testing and specific IgE assays are not helpful.
Also consider gastroesophageal reflux. Children whose symptoms do not improve with proton pump inhibitors might have eosinophilic esophagitis. A food allergen sometimes triggers this condition, and consultation with a gastroenterologist and a biopsy are the best clinical strategies.
It is appropriate for a general pediatrician to treat children with a food allergy when the source of the reaction is easily identifiable, when their symptoms are consistent with an allergic reaction, and when their condition is non–life threatening (and supported by specific IgE test results, if obtained).
Avoidance of the culprit allergen is essential to management. Stress the importance of reading all food labels. Self-injectable epinephrine (such as Mylan Inc.'s EpiPen or EpiPen Jr.) is another essential component. Instruct patients on how and when to use epinephrine, including what to do when anaphylaxis starts in school or in a day care setting. In some cases, it may be appropriate to suggest that the patient wear a medical alert bracelet or necklace.
Education is probably the most important factor in management. Talk to patients and families about prognosis, cross-reactive allergens, and the nutritional needs of patients with multiple food allergies. Keep in mind that if the list of foods to avoid is extensive, this may interfere with normal growth and development. A dietician can help educate families not only on what foods to avoid, but on what foods are encouraged.
Make sure parents are comfortable with your treatment plan. If you are confident in your identification of the culprit food, you can implement a food-elimination diet based on details from the history. Prescribe the appropriate dose of epinephrine and outline an anaphylaxis plan (easily found on the Web site www.foodallergy.org
Pediatricians can order in vitro specific IgE blood tests such as Phadia AB's Pharmacia CAP or UniCAP. These are helpful when performed by a reliable laboratory and may obviate the need for the skin testing of some patients for some foods. These tests are relatively good predictors of peanut, milk, and egg allergies.
In contrast, total IgE and complete blood count assays generally are not helpful. Performance of specific IgE blood tests to foods that are known to be clinically tolerated should be avoided; this just leads to confusion by all parties. In addition, avoid testing for specific IgG to foods because this strategy is not helpful for diagnosis. IgG is a measure of exposure only, and therefore positive results are not uncommon.
Most commonly, I see food-allergic patients post diagnosis to explain the results of previous tests and to develop an ongoing plan for avoidance, which includes strategies in the case of future accidental exposure.
If tolerance is suspected, I discuss with children and parents when to consider a food challenge. Such a protocol is probably best performed at a specialist's office, particularly if a more comprehensive, double-blind, placebo-controlled challenge is warranted. Food challenges require significant time and resources, including advance preparations in case anaphylaxis occurs.
Also consider referral to a specialist when a food culprit is not easily identified; when there is disparity between diagnostic test findings and patient history; and when the patient and family require more comprehensive education.
Pediatricians play an integral role in the initial diagnosis and management of children with a suspected food allergy. History, some useful laboratory tests, and careful counseling can go a long way to identify these sometimes challenging patients.
A considerable amount of anxiety often surrounds food allergy concerns, and this should be addressed (or at least acknowledged) with patients and their families.
Start with history, the most important diagnostic factor: Ask children and parents about specific symptoms, their timing, and foods the child has ingested. If the child experienced anaphylaxis, then include medication and insect stings in your history taking. The good news for primary care is that 90% of food allergies are caused by a few foods: milk, egg, wheat, soy, peanut, fish, shellfish, and nuts. Other triggers are relatively rare.
Allergy skin testing and/or specific immunoglobulin E (IgE) blood tests can support your diagnosis. However, these findings need to be correlated with history because false-positive results occur frequently. It is important to realize that the level of specific IgE to a food is not correlated with the severity of a reaction, but instead is correlated with the likelihood of having a single reaction.
Determine if the child's symptoms truly suggest an allergic reaction or instead point to a non–food-related cause. Psychological conditions such bulimia, anorexia, or factitious disorder can mimic a food allergy, for example.
Your differential diagnosis also includes structural abnormalities of the GI tract; cystic fibrosis with chronic diarrhea from pancreatic insufficiency; and illness caused by contaminants and additives such as flavorings, dyes, preservatives, or infectious organisms. Also check for exposure to pharmacologic contaminants such as caffeine or tyramine in certain foods.
Rule out lactose intolerance and other disaccharidase deficiencies (especially if the symptoms are limited to the GI tract) and a non-IgE reaction called food protein-induced enterocolitis syndrome (FPIES). An FPIES diagnosis is based on clinical presentation and symptoms because allergy skin testing and specific IgE assays are not helpful.
Also consider gastroesophageal reflux. Children whose symptoms do not improve with proton pump inhibitors might have eosinophilic esophagitis. A food allergen sometimes triggers this condition, and consultation with a gastroenterologist and a biopsy are the best clinical strategies.
It is appropriate for a general pediatrician to treat children with a food allergy when the source of the reaction is easily identifiable, when their symptoms are consistent with an allergic reaction, and when their condition is non–life threatening (and supported by specific IgE test results, if obtained).
Avoidance of the culprit allergen is essential to management. Stress the importance of reading all food labels. Self-injectable epinephrine (such as Mylan Inc.'s EpiPen or EpiPen Jr.) is another essential component. Instruct patients on how and when to use epinephrine, including what to do when anaphylaxis starts in school or in a day care setting. In some cases, it may be appropriate to suggest that the patient wear a medical alert bracelet or necklace.
Education is probably the most important factor in management. Talk to patients and families about prognosis, cross-reactive allergens, and the nutritional needs of patients with multiple food allergies. Keep in mind that if the list of foods to avoid is extensive, this may interfere with normal growth and development. A dietician can help educate families not only on what foods to avoid, but on what foods are encouraged.
Make sure parents are comfortable with your treatment plan. If you are confident in your identification of the culprit food, you can implement a food-elimination diet based on details from the history. Prescribe the appropriate dose of epinephrine and outline an anaphylaxis plan (easily found on the Web site www.foodallergy.org
Pediatricians can order in vitro specific IgE blood tests such as Phadia AB's Pharmacia CAP or UniCAP. These are helpful when performed by a reliable laboratory and may obviate the need for the skin testing of some patients for some foods. These tests are relatively good predictors of peanut, milk, and egg allergies.
In contrast, total IgE and complete blood count assays generally are not helpful. Performance of specific IgE blood tests to foods that are known to be clinically tolerated should be avoided; this just leads to confusion by all parties. In addition, avoid testing for specific IgG to foods because this strategy is not helpful for diagnosis. IgG is a measure of exposure only, and therefore positive results are not uncommon.
Most commonly, I see food-allergic patients post diagnosis to explain the results of previous tests and to develop an ongoing plan for avoidance, which includes strategies in the case of future accidental exposure.
If tolerance is suspected, I discuss with children and parents when to consider a food challenge. Such a protocol is probably best performed at a specialist's office, particularly if a more comprehensive, double-blind, placebo-controlled challenge is warranted. Food challenges require significant time and resources, including advance preparations in case anaphylaxis occurs.
Also consider referral to a specialist when a food culprit is not easily identified; when there is disparity between diagnostic test findings and patient history; and when the patient and family require more comprehensive education.
Pediatricians play an integral role in the initial diagnosis and management of children with a suspected food allergy. History, some useful laboratory tests, and careful counseling can go a long way to identify these sometimes challenging patients.
A considerable amount of anxiety often surrounds food allergy concerns, and this should be addressed (or at least acknowledged) with patients and their families.
Start with history, the most important diagnostic factor: Ask children and parents about specific symptoms, their timing, and foods the child has ingested. If the child experienced anaphylaxis, then include medication and insect stings in your history taking. The good news for primary care is that 90% of food allergies are caused by a few foods: milk, egg, wheat, soy, peanut, fish, shellfish, and nuts. Other triggers are relatively rare.
Allergy skin testing and/or specific immunoglobulin E (IgE) blood tests can support your diagnosis. However, these findings need to be correlated with history because false-positive results occur frequently. It is important to realize that the level of specific IgE to a food is not correlated with the severity of a reaction, but instead is correlated with the likelihood of having a single reaction.
Determine if the child's symptoms truly suggest an allergic reaction or instead point to a non–food-related cause. Psychological conditions such bulimia, anorexia, or factitious disorder can mimic a food allergy, for example.
Your differential diagnosis also includes structural abnormalities of the GI tract; cystic fibrosis with chronic diarrhea from pancreatic insufficiency; and illness caused by contaminants and additives such as flavorings, dyes, preservatives, or infectious organisms. Also check for exposure to pharmacologic contaminants such as caffeine or tyramine in certain foods.
Rule out lactose intolerance and other disaccharidase deficiencies (especially if the symptoms are limited to the GI tract) and a non-IgE reaction called food protein-induced enterocolitis syndrome (FPIES). An FPIES diagnosis is based on clinical presentation and symptoms because allergy skin testing and specific IgE assays are not helpful.
Also consider gastroesophageal reflux. Children whose symptoms do not improve with proton pump inhibitors might have eosinophilic esophagitis. A food allergen sometimes triggers this condition, and consultation with a gastroenterologist and a biopsy are the best clinical strategies.
It is appropriate for a general pediatrician to treat children with a food allergy when the source of the reaction is easily identifiable, when their symptoms are consistent with an allergic reaction, and when their condition is non–life threatening (and supported by specific IgE test results, if obtained).
Avoidance of the culprit allergen is essential to management. Stress the importance of reading all food labels. Self-injectable epinephrine (such as Mylan Inc.'s EpiPen or EpiPen Jr.) is another essential component. Instruct patients on how and when to use epinephrine, including what to do when anaphylaxis starts in school or in a day care setting. In some cases, it may be appropriate to suggest that the patient wear a medical alert bracelet or necklace.
Education is probably the most important factor in management. Talk to patients and families about prognosis, cross-reactive allergens, and the nutritional needs of patients with multiple food allergies. Keep in mind that if the list of foods to avoid is extensive, this may interfere with normal growth and development. A dietician can help educate families not only on what foods to avoid, but on what foods are encouraged.
Make sure parents are comfortable with your treatment plan. If you are confident in your identification of the culprit food, you can implement a food-elimination diet based on details from the history. Prescribe the appropriate dose of epinephrine and outline an anaphylaxis plan (easily found on the Web site www.foodallergy.org
Pediatricians can order in vitro specific IgE blood tests such as Phadia AB's Pharmacia CAP or UniCAP. These are helpful when performed by a reliable laboratory and may obviate the need for the skin testing of some patients for some foods. These tests are relatively good predictors of peanut, milk, and egg allergies.
In contrast, total IgE and complete blood count assays generally are not helpful. Performance of specific IgE blood tests to foods that are known to be clinically tolerated should be avoided; this just leads to confusion by all parties. In addition, avoid testing for specific IgG to foods because this strategy is not helpful for diagnosis. IgG is a measure of exposure only, and therefore positive results are not uncommon.
Most commonly, I see food-allergic patients post diagnosis to explain the results of previous tests and to develop an ongoing plan for avoidance, which includes strategies in the case of future accidental exposure.
If tolerance is suspected, I discuss with children and parents when to consider a food challenge. Such a protocol is probably best performed at a specialist's office, particularly if a more comprehensive, double-blind, placebo-controlled challenge is warranted. Food challenges require significant time and resources, including advance preparations in case anaphylaxis occurs.
Also consider referral to a specialist when a food culprit is not easily identified; when there is disparity between diagnostic test findings and patient history; and when the patient and family require more comprehensive education.
Antipsychotics Spur Rapid Metabolic Changes
NEW ORLEANS — Worrisome and clinically measurable metabolic changes can be seen in just 12 weeks among children and adolescents who received antipsychotic medications in a National Institutes of Health–sponsored study, prompting serious concern among clinicians who learned of the results at the annual meeting.
The results struck at the heart of a troubling dichotomy: an explosion of prescriptions of antipsychotic medications for children, but little evidence in real-world practice that young patients are being routinely screened for metabolic changes that have the potential to shorten life expectancy.
The ongoing Metabolic Effects of Antipsychotics in Children study has already enrolled more than 140 children aged 7–18 years who had been slated to be placed on antipsychotics in the community. Investigators closely monitored changes over a 3-month period in body fat using dual-energy x-ray absorptiometry (DXA) and insulin sensitivity using gold standard methods. They also trackeding clinically available measures such as body mass index (BMI) percentile, and plasma glucose and lipids.
Body fat percentages rose in “not all, but certainly the majority of these children and youth,” said Dr. John W. Newcomer, professor of psychiatry and medicine and director of the center for clinical studies at Washington University in St. Louis.
Mean increases were highly variable among children and adolescents taking antipsychotic medications, but have averaged almost 3 kilos, or 6.5 pounds, “of body fat, not just weight,” in just 12 weeks, he said.
Some variance was seen in mean percent body fat accrual depending on which antipsychotic medication the children and adolescents received in the randomized open-label study.
However, box plots revealed “substantial overlap” in the results, showing that each individual child's metabolic response to a given drug is somewhat unpredictable.
“You can find kids who take any one of these medications and potentially get a substantial increase in body fat, and you can also find kids who take any one of these agents who actually have very little change in body fat, although some medications are associated with a higher risk of substantial increase,” Dr. Newcomer said.
Increases in BMI percentiles were “substantial” as well, and closely paralleled more sophisticated measures of body fat, such as DXA.
“The good news is, it's pretty easy to track the changes in adiposity,” said Dr. Newcomer in an interview following the meeting.
“We used very fancy and expensive measures of body fat, but what pediatricians have in the front of every kid's chart (the BMI percentage table) does a darned good job of not only lining up where the child is at the baseline screen, but also in tracking changes over time.”
In a similar vein, the study found that simple blood cholesterol profiles—especially triglycerides and HDL—did a “halfway decent job” of estimating insulin sensitivity at baseline and then tracking changes through the early months of therapy, Dr. Newcomer added.
“The point is … don't wait a year to check the labs,” he said. “Don't not look.”
What is troubling to many is the fact that many clinicians indeed are not looking.
A Medicaid claims data study published earlier this year found that glucose screening was performed in just 31.6% and lipid testing in just 13.4% of 5,370 children aged 6–17 years prescribed antipsychotic drugs from July 1, 2004, to June 30, 2006 (Arch. Pediatr. Adolesc. Med. 2010;164:344–51).
Dr. Newcomer, a coauthor on the Medicaid claims research, said a growing number of “very eye-opening studies” about the enduring impact of childhood metabolic dysregulation and obesity should make clinicians weigh risks and consequences carefully when choosing drugs to prescribe for childhood schizophrenia, and perhaps even more so for use in disruptive behavior disorders and other nonpsychotic diagnoses.
“I have certainly learned that there are children at the end of the road of clinical options who are either not going to be in school or [are] unable to participate without some heroic treatment measures, such as low-dose antipsychotic treatment, to help them to re-engage in education,” he commented.
At the same time, relatively brief pharmacologic interventions for children who do not have schizophrenia or bipolar disorder should leave “a metabolic footprint … as modest as possible,” he said.
The Washington University study extended body weight findings from the nonrandomized SATIETY study published last year (JAMA 2009;302:1765–73), in which 272 4- to 19-year-olds prescribed antipsychotic drugs gained from a mean 4.4 kg (aripiprazole) to 8.5 kg (olanzapine) in a median of just 10.8 weeks on medication.
At the APA scientific session where interim data were released from the MEAC study, one audience member rose to call the findings “catastrophic.”
“What you're showing us is very, very scary,” he told Dr. Newcomer, who replied that the metabolic impacts of other classes of drugs widely used in children, including benzodiazepines and high-dose antidepressants, are also potentially concerning.
“We're having this policy debate under a streetlamp as though second-generation antipsychotics are the only drugs that cause weight gain,” Dr. Newcomer said. “Let's not kid ourselves.”
One alternative raised at the session was intensive behavioral modification, such as a yearlong, school-based program for disruptive children described by Dr. Jacob Venter of Wellesley, Mass., and his colleagues at the same APA scientific session.
Dr. Newcomer pointed to the University of Arizona behavioral study as an example of how nonpharmacologic interventions can produce “some good results,” even among children with severe behavioral dysregulation.
“The problem is, I don't know about your town, but in St. Louis, there is a 6-month waiting list to see a child psychiatrist,” he told the audience.
By the time they can be seen, “these families are in great distress and sometimes aren't terribly interested in taking those referrals for behavioral treatments, either because they already tried some therapy or because they seek rapid change,” he said.
Families want the quick responses they associate with medication, and when a trial of behavioral modification is suggested as a starting place, “we can't give it away.”
As for trying to reduce prescribing of antipsychotic medications to children, particularly among those who do not have symptoms consistent with bipolar disorder or schizophrenia, Dr. Newcomer, who also chairs Missouri's Drug Utilization Review Board, was somewhat skeptical about the potential to substantially reduce that clinical practice.
“Like it or not, that horse is out of the barn. The clinical benefits can be obvious to parents, children, and their doctors, so there will continue to be interest in this therapeutic approach, even as we fully elaborate the risks. This is happening all over the country. The rates of prescriptions are going up. The off-label use is tremendous, suggesting a lot of unmet need,” he said.
Indeed, a series of studies conducted by a team led by Dr. Mark Olfson at Columbia University, New York, has found that prescribing of antipsychotic medications by psychiatrists and primary care physicians has skyrocketed in the United States since the mid-1990s, with treatment of disruptive behavior disorders, including attention-deficit/hyperactivity disorder, playing a significant role in the increase.
In one example, Dr. Olfson reported that antipsychotic use by 2- to 5-year-olds covered by private insurance rose from 0.78/1,000 to 1.59/1,000 from 1999 to 2007.
Less than half of the children in the study had received a mental health assessment, a psychotherapy visit, or a consultation with a psychiatrist.
Antipsychotic medication was prescribed in more than 1.2 million outpatient office visits by children in 2002, up from 201,000 in 1993, Dr. Olfson reported (Arch. Gen. Psychiatry 2006;63:679–85). Diagnoses of disruptive behavior disorders (37.8%), mood disorders (31.8%), pervasive developmental disorders or mental retardation (17.3%), and psychotic disorders (14.2%) accounted for most of those visits.
Dr. Newcomer disclosed that he has served as a consultant to several pharmaceutical companies but reported no financial conflicts of interest relevant to his study.
NEW ORLEANS — Worrisome and clinically measurable metabolic changes can be seen in just 12 weeks among children and adolescents who received antipsychotic medications in a National Institutes of Health–sponsored study, prompting serious concern among clinicians who learned of the results at the annual meeting.
The results struck at the heart of a troubling dichotomy: an explosion of prescriptions of antipsychotic medications for children, but little evidence in real-world practice that young patients are being routinely screened for metabolic changes that have the potential to shorten life expectancy.
The ongoing Metabolic Effects of Antipsychotics in Children study has already enrolled more than 140 children aged 7–18 years who had been slated to be placed on antipsychotics in the community. Investigators closely monitored changes over a 3-month period in body fat using dual-energy x-ray absorptiometry (DXA) and insulin sensitivity using gold standard methods. They also trackeding clinically available measures such as body mass index (BMI) percentile, and plasma glucose and lipids.
Body fat percentages rose in “not all, but certainly the majority of these children and youth,” said Dr. John W. Newcomer, professor of psychiatry and medicine and director of the center for clinical studies at Washington University in St. Louis.
Mean increases were highly variable among children and adolescents taking antipsychotic medications, but have averaged almost 3 kilos, or 6.5 pounds, “of body fat, not just weight,” in just 12 weeks, he said.
Some variance was seen in mean percent body fat accrual depending on which antipsychotic medication the children and adolescents received in the randomized open-label study.
However, box plots revealed “substantial overlap” in the results, showing that each individual child's metabolic response to a given drug is somewhat unpredictable.
“You can find kids who take any one of these medications and potentially get a substantial increase in body fat, and you can also find kids who take any one of these agents who actually have very little change in body fat, although some medications are associated with a higher risk of substantial increase,” Dr. Newcomer said.
Increases in BMI percentiles were “substantial” as well, and closely paralleled more sophisticated measures of body fat, such as DXA.
“The good news is, it's pretty easy to track the changes in adiposity,” said Dr. Newcomer in an interview following the meeting.
“We used very fancy and expensive measures of body fat, but what pediatricians have in the front of every kid's chart (the BMI percentage table) does a darned good job of not only lining up where the child is at the baseline screen, but also in tracking changes over time.”
In a similar vein, the study found that simple blood cholesterol profiles—especially triglycerides and HDL—did a “halfway decent job” of estimating insulin sensitivity at baseline and then tracking changes through the early months of therapy, Dr. Newcomer added.
“The point is … don't wait a year to check the labs,” he said. “Don't not look.”
What is troubling to many is the fact that many clinicians indeed are not looking.
A Medicaid claims data study published earlier this year found that glucose screening was performed in just 31.6% and lipid testing in just 13.4% of 5,370 children aged 6–17 years prescribed antipsychotic drugs from July 1, 2004, to June 30, 2006 (Arch. Pediatr. Adolesc. Med. 2010;164:344–51).
Dr. Newcomer, a coauthor on the Medicaid claims research, said a growing number of “very eye-opening studies” about the enduring impact of childhood metabolic dysregulation and obesity should make clinicians weigh risks and consequences carefully when choosing drugs to prescribe for childhood schizophrenia, and perhaps even more so for use in disruptive behavior disorders and other nonpsychotic diagnoses.
“I have certainly learned that there are children at the end of the road of clinical options who are either not going to be in school or [are] unable to participate without some heroic treatment measures, such as low-dose antipsychotic treatment, to help them to re-engage in education,” he commented.
At the same time, relatively brief pharmacologic interventions for children who do not have schizophrenia or bipolar disorder should leave “a metabolic footprint … as modest as possible,” he said.
The Washington University study extended body weight findings from the nonrandomized SATIETY study published last year (JAMA 2009;302:1765–73), in which 272 4- to 19-year-olds prescribed antipsychotic drugs gained from a mean 4.4 kg (aripiprazole) to 8.5 kg (olanzapine) in a median of just 10.8 weeks on medication.
At the APA scientific session where interim data were released from the MEAC study, one audience member rose to call the findings “catastrophic.”
“What you're showing us is very, very scary,” he told Dr. Newcomer, who replied that the metabolic impacts of other classes of drugs widely used in children, including benzodiazepines and high-dose antidepressants, are also potentially concerning.
“We're having this policy debate under a streetlamp as though second-generation antipsychotics are the only drugs that cause weight gain,” Dr. Newcomer said. “Let's not kid ourselves.”
One alternative raised at the session was intensive behavioral modification, such as a yearlong, school-based program for disruptive children described by Dr. Jacob Venter of Wellesley, Mass., and his colleagues at the same APA scientific session.
Dr. Newcomer pointed to the University of Arizona behavioral study as an example of how nonpharmacologic interventions can produce “some good results,” even among children with severe behavioral dysregulation.
“The problem is, I don't know about your town, but in St. Louis, there is a 6-month waiting list to see a child psychiatrist,” he told the audience.
By the time they can be seen, “these families are in great distress and sometimes aren't terribly interested in taking those referrals for behavioral treatments, either because they already tried some therapy or because they seek rapid change,” he said.
Families want the quick responses they associate with medication, and when a trial of behavioral modification is suggested as a starting place, “we can't give it away.”
As for trying to reduce prescribing of antipsychotic medications to children, particularly among those who do not have symptoms consistent with bipolar disorder or schizophrenia, Dr. Newcomer, who also chairs Missouri's Drug Utilization Review Board, was somewhat skeptical about the potential to substantially reduce that clinical practice.
“Like it or not, that horse is out of the barn. The clinical benefits can be obvious to parents, children, and their doctors, so there will continue to be interest in this therapeutic approach, even as we fully elaborate the risks. This is happening all over the country. The rates of prescriptions are going up. The off-label use is tremendous, suggesting a lot of unmet need,” he said.
Indeed, a series of studies conducted by a team led by Dr. Mark Olfson at Columbia University, New York, has found that prescribing of antipsychotic medications by psychiatrists and primary care physicians has skyrocketed in the United States since the mid-1990s, with treatment of disruptive behavior disorders, including attention-deficit/hyperactivity disorder, playing a significant role in the increase.
In one example, Dr. Olfson reported that antipsychotic use by 2- to 5-year-olds covered by private insurance rose from 0.78/1,000 to 1.59/1,000 from 1999 to 2007.
Less than half of the children in the study had received a mental health assessment, a psychotherapy visit, or a consultation with a psychiatrist.
Antipsychotic medication was prescribed in more than 1.2 million outpatient office visits by children in 2002, up from 201,000 in 1993, Dr. Olfson reported (Arch. Gen. Psychiatry 2006;63:679–85). Diagnoses of disruptive behavior disorders (37.8%), mood disorders (31.8%), pervasive developmental disorders or mental retardation (17.3%), and psychotic disorders (14.2%) accounted for most of those visits.
Dr. Newcomer disclosed that he has served as a consultant to several pharmaceutical companies but reported no financial conflicts of interest relevant to his study.
NEW ORLEANS — Worrisome and clinically measurable metabolic changes can be seen in just 12 weeks among children and adolescents who received antipsychotic medications in a National Institutes of Health–sponsored study, prompting serious concern among clinicians who learned of the results at the annual meeting.
The results struck at the heart of a troubling dichotomy: an explosion of prescriptions of antipsychotic medications for children, but little evidence in real-world practice that young patients are being routinely screened for metabolic changes that have the potential to shorten life expectancy.
The ongoing Metabolic Effects of Antipsychotics in Children study has already enrolled more than 140 children aged 7–18 years who had been slated to be placed on antipsychotics in the community. Investigators closely monitored changes over a 3-month period in body fat using dual-energy x-ray absorptiometry (DXA) and insulin sensitivity using gold standard methods. They also trackeding clinically available measures such as body mass index (BMI) percentile, and plasma glucose and lipids.
Body fat percentages rose in “not all, but certainly the majority of these children and youth,” said Dr. John W. Newcomer, professor of psychiatry and medicine and director of the center for clinical studies at Washington University in St. Louis.
Mean increases were highly variable among children and adolescents taking antipsychotic medications, but have averaged almost 3 kilos, or 6.5 pounds, “of body fat, not just weight,” in just 12 weeks, he said.
Some variance was seen in mean percent body fat accrual depending on which antipsychotic medication the children and adolescents received in the randomized open-label study.
However, box plots revealed “substantial overlap” in the results, showing that each individual child's metabolic response to a given drug is somewhat unpredictable.
“You can find kids who take any one of these medications and potentially get a substantial increase in body fat, and you can also find kids who take any one of these agents who actually have very little change in body fat, although some medications are associated with a higher risk of substantial increase,” Dr. Newcomer said.
Increases in BMI percentiles were “substantial” as well, and closely paralleled more sophisticated measures of body fat, such as DXA.
“The good news is, it's pretty easy to track the changes in adiposity,” said Dr. Newcomer in an interview following the meeting.
“We used very fancy and expensive measures of body fat, but what pediatricians have in the front of every kid's chart (the BMI percentage table) does a darned good job of not only lining up where the child is at the baseline screen, but also in tracking changes over time.”
In a similar vein, the study found that simple blood cholesterol profiles—especially triglycerides and HDL—did a “halfway decent job” of estimating insulin sensitivity at baseline and then tracking changes through the early months of therapy, Dr. Newcomer added.
“The point is … don't wait a year to check the labs,” he said. “Don't not look.”
What is troubling to many is the fact that many clinicians indeed are not looking.
A Medicaid claims data study published earlier this year found that glucose screening was performed in just 31.6% and lipid testing in just 13.4% of 5,370 children aged 6–17 years prescribed antipsychotic drugs from July 1, 2004, to June 30, 2006 (Arch. Pediatr. Adolesc. Med. 2010;164:344–51).
Dr. Newcomer, a coauthor on the Medicaid claims research, said a growing number of “very eye-opening studies” about the enduring impact of childhood metabolic dysregulation and obesity should make clinicians weigh risks and consequences carefully when choosing drugs to prescribe for childhood schizophrenia, and perhaps even more so for use in disruptive behavior disorders and other nonpsychotic diagnoses.
“I have certainly learned that there are children at the end of the road of clinical options who are either not going to be in school or [are] unable to participate without some heroic treatment measures, such as low-dose antipsychotic treatment, to help them to re-engage in education,” he commented.
At the same time, relatively brief pharmacologic interventions for children who do not have schizophrenia or bipolar disorder should leave “a metabolic footprint … as modest as possible,” he said.
The Washington University study extended body weight findings from the nonrandomized SATIETY study published last year (JAMA 2009;302:1765–73), in which 272 4- to 19-year-olds prescribed antipsychotic drugs gained from a mean 4.4 kg (aripiprazole) to 8.5 kg (olanzapine) in a median of just 10.8 weeks on medication.
At the APA scientific session where interim data were released from the MEAC study, one audience member rose to call the findings “catastrophic.”
“What you're showing us is very, very scary,” he told Dr. Newcomer, who replied that the metabolic impacts of other classes of drugs widely used in children, including benzodiazepines and high-dose antidepressants, are also potentially concerning.
“We're having this policy debate under a streetlamp as though second-generation antipsychotics are the only drugs that cause weight gain,” Dr. Newcomer said. “Let's not kid ourselves.”
One alternative raised at the session was intensive behavioral modification, such as a yearlong, school-based program for disruptive children described by Dr. Jacob Venter of Wellesley, Mass., and his colleagues at the same APA scientific session.
Dr. Newcomer pointed to the University of Arizona behavioral study as an example of how nonpharmacologic interventions can produce “some good results,” even among children with severe behavioral dysregulation.
“The problem is, I don't know about your town, but in St. Louis, there is a 6-month waiting list to see a child psychiatrist,” he told the audience.
By the time they can be seen, “these families are in great distress and sometimes aren't terribly interested in taking those referrals for behavioral treatments, either because they already tried some therapy or because they seek rapid change,” he said.
Families want the quick responses they associate with medication, and when a trial of behavioral modification is suggested as a starting place, “we can't give it away.”
As for trying to reduce prescribing of antipsychotic medications to children, particularly among those who do not have symptoms consistent with bipolar disorder or schizophrenia, Dr. Newcomer, who also chairs Missouri's Drug Utilization Review Board, was somewhat skeptical about the potential to substantially reduce that clinical practice.
“Like it or not, that horse is out of the barn. The clinical benefits can be obvious to parents, children, and their doctors, so there will continue to be interest in this therapeutic approach, even as we fully elaborate the risks. This is happening all over the country. The rates of prescriptions are going up. The off-label use is tremendous, suggesting a lot of unmet need,” he said.
Indeed, a series of studies conducted by a team led by Dr. Mark Olfson at Columbia University, New York, has found that prescribing of antipsychotic medications by psychiatrists and primary care physicians has skyrocketed in the United States since the mid-1990s, with treatment of disruptive behavior disorders, including attention-deficit/hyperactivity disorder, playing a significant role in the increase.
In one example, Dr. Olfson reported that antipsychotic use by 2- to 5-year-olds covered by private insurance rose from 0.78/1,000 to 1.59/1,000 from 1999 to 2007.
Less than half of the children in the study had received a mental health assessment, a psychotherapy visit, or a consultation with a psychiatrist.
Antipsychotic medication was prescribed in more than 1.2 million outpatient office visits by children in 2002, up from 201,000 in 1993, Dr. Olfson reported (Arch. Gen. Psychiatry 2006;63:679–85). Diagnoses of disruptive behavior disorders (37.8%), mood disorders (31.8%), pervasive developmental disorders or mental retardation (17.3%), and psychotic disorders (14.2%) accounted for most of those visits.
Dr. Newcomer disclosed that he has served as a consultant to several pharmaceutical companies but reported no financial conflicts of interest relevant to his study.
Help Parents Change Style for Raising Teens
www.CHADIS.com[email protected]
Adolescents are often the most intimidating of our patients. Let's face it: Most of us chose pediatrics because we like little kids. If a 15-minute office visit with a sullen teenager can be so difficult, imagine living with one 24/7. Actually, many of us won't have to imagine—we ourselves are the parents of adolescents, and we know just how challenging that can be.
Despite our own feelings of inadequacy, we can help parents make the transition from raising the innocent younger child to guiding the testy teen into adulthood. A failure to make that transition in parenting style can contribute greatly to a suboptimal outcome.
But your guidance needs to start early. When a parent comes into the office demanding that you administer a drug test or a pregnancy test, you have probably missed the window for effective action. The horse is well out of the barn.
The time to start is earlier—much earlier. All of parenting involves the balancing act between supporting dependency and promoting independence. When people first become parents, they are consumed with accepting the huge dependency of their baby. As the child gets older, parents must allow the child more independence for things to go smoothly.
But adolescence is a time when that balancing act requires truly skilled acrobatics. Teens and their parents need to negotiate the “Four I's” of adolescent development: Initiative, Individuation, Independence, and Intimacy.
Adolescents clearly need to take the initiative in their activities, including when they do their chores and how they manage homework. If parents get in the way and try to structure all of that, they're going to get a lot of pushback.
In terms of individuation—discovering who they are—teenagers are highly sensitive to the standards of peers. They're more interested in what their peers think they should do than what their parents think they should do. On one level, this includes how many ear piercings they have and how they dress. But on a broader level, they need to think their parents are wrong about most things in order to feel “like their own person.” Offering an opinion can be beneficial in giving the adolescent something to counter, but ideally save consequences for more substantial failings. In terms of independence, teenagers are better educated by learning from the consequences of their own actions when those actions are not harmful to their futures.
And in terms of intimacy, teens want and need privacy for their budding relationships. Parents need to learn how to be available to talk about relationships, but not ask too many questions.
Different teens move through these changes at different times. And on top of that, the transition may not always go in one direction. A teen may want to be very independent in choosing her clothes. But the same teen may want a lot of parental help on getting her homework done and on handling peer situations. That's part of what makes parenting adolescents so difficult.
Parents need to gradually release control and let their teens exert more independence. But the key word in that sentence is “gradually,” and parents need to be alert for signs that the child is not ready or has not yet earned that freedom.
Let's say the parents have allowed their 13-year-old to have a cell phone. Let's say that a few weeks later, the child hurls the phone against the wall in anger, shattering it beyond repair. Some parents might be tempted to say: “That's it. I'm not buying you another cell phone until you're in college,” but that is unlikely to be the most educational solution. The time frame should be measured in days or weeks, not in months or years. If consequences are too severe, kids tend to write their parents off completely and feel they have been written off.
Instead, the parents should give the teen a clear path to re-earning the privilege, negotiating the terms. Maybe he has to contribute 80% of his allowance and do some extra chores until the phone is paid for. Showing that they're reasonable and willing to negotiate is a model of adult behavior, and it's also their key to success.
The older the child, the more important it is to negotiate what the rules are to be, and also what exceptions there might be. It's fine if there's a general rule that they can't stay out after 11 o'clock. But if a special event comes along that starts at 10 o'clock and won't end until 2 a.m., it's best to be flexible about the curfew this one time. When teens and parents negotiate one-time exceptions as needed, there is structure but rebellion or sneaking is not brought out.
Negotiation is important. A 30-year longitudinal study from the University of California, Berkeley, demonstrated that parents who managed to negotiate the rules with their children had more harmonious relationships with them later (New Dir. Child Adolesc. Dev. 2005;108:61–9). Often a dynamic arises in families where the parents are so generally annoyed with their teen that they reflexively answer, “No!” to any request. That can be really counterproductive when it comes to parenting adolescents. The first response should be: “Yes, if at all possible. Let's talk about it.”
I recommend that parents explicitly discuss the request using the following six points in deciding with the adolescent on their request. Posting these on the refrigerator and making discussing them a routine lets the teen know they are being taken seriously, slows the reflex to say “no,” and may help install them as a mantra in the teen's brain for future decision making:
Six Guides for Decision Making
1. Is it safe?
2. Is it legal?
3. Does it conflict with responsibilities?
4. Does it meet a developmental need?
5. Does it interfere with others?
6. Could it harm his/her development?
Anyone who's read “The Catcher in the Rye” (New York: Little, Brown and Co., 1951) by J.D. Salinger knows that teenagers are especially sensitive to hypocrisy. Parents often talk about the importance of being a moral person, but the teen is aware that they're cheating on their income taxes. They will reject their parents' moral code if they see them being hypocritical.
Clearly, the best way for the parent to encourage their offspring to uphold good moral standards is to actually live those standards 24/7. But almost everyone fails to live up to those standards from time to time, and if they're parents of an adolescent, the teen is sure to be right there when they do. Adolescents appreciate and learn from honesty when that happens. The parent could admit, “Yes, I know I said that you should never curse another driver, but I was so angry that I forgot my own rule.”
In these days of one- and two-child families, where parents often depend on their own children for friendship and companionship, it can be especially devastating to hear a teen say: “I hate you. You're the worst parents ever.” When that happens—and it's almost certain to happen, since it's the rare child who never utters such a sentiment—the parent's best response is not to rise to the bait of an angry teenager. They don't really mean it. And if the parent shows too much visible distress, or starts to punish them for saying those things, there won't be as much opportunity to recover. A simple “I am sorry you feel that way right now. I can see that you are really angry about [my decision, your curfew, what I said].”
And when the teen notices that the parent has not reacted to such provocation, that in itself is a valuable life lesson. The next time a street tough tosses off an insult, he'll be more likely to simply shrug his shoulders and walk away. For additional information on dealing with adolescents, the American Academy of Pediatrics maintains a particularly good collection of resources for parents at www.healthychildren.org
www.CHADIS.com[email protected]
Adolescents are often the most intimidating of our patients. Let's face it: Most of us chose pediatrics because we like little kids. If a 15-minute office visit with a sullen teenager can be so difficult, imagine living with one 24/7. Actually, many of us won't have to imagine—we ourselves are the parents of adolescents, and we know just how challenging that can be.
Despite our own feelings of inadequacy, we can help parents make the transition from raising the innocent younger child to guiding the testy teen into adulthood. A failure to make that transition in parenting style can contribute greatly to a suboptimal outcome.
But your guidance needs to start early. When a parent comes into the office demanding that you administer a drug test or a pregnancy test, you have probably missed the window for effective action. The horse is well out of the barn.
The time to start is earlier—much earlier. All of parenting involves the balancing act between supporting dependency and promoting independence. When people first become parents, they are consumed with accepting the huge dependency of their baby. As the child gets older, parents must allow the child more independence for things to go smoothly.
But adolescence is a time when that balancing act requires truly skilled acrobatics. Teens and their parents need to negotiate the “Four I's” of adolescent development: Initiative, Individuation, Independence, and Intimacy.
Adolescents clearly need to take the initiative in their activities, including when they do their chores and how they manage homework. If parents get in the way and try to structure all of that, they're going to get a lot of pushback.
In terms of individuation—discovering who they are—teenagers are highly sensitive to the standards of peers. They're more interested in what their peers think they should do than what their parents think they should do. On one level, this includes how many ear piercings they have and how they dress. But on a broader level, they need to think their parents are wrong about most things in order to feel “like their own person.” Offering an opinion can be beneficial in giving the adolescent something to counter, but ideally save consequences for more substantial failings. In terms of independence, teenagers are better educated by learning from the consequences of their own actions when those actions are not harmful to their futures.
And in terms of intimacy, teens want and need privacy for their budding relationships. Parents need to learn how to be available to talk about relationships, but not ask too many questions.
Different teens move through these changes at different times. And on top of that, the transition may not always go in one direction. A teen may want to be very independent in choosing her clothes. But the same teen may want a lot of parental help on getting her homework done and on handling peer situations. That's part of what makes parenting adolescents so difficult.
Parents need to gradually release control and let their teens exert more independence. But the key word in that sentence is “gradually,” and parents need to be alert for signs that the child is not ready or has not yet earned that freedom.
Let's say the parents have allowed their 13-year-old to have a cell phone. Let's say that a few weeks later, the child hurls the phone against the wall in anger, shattering it beyond repair. Some parents might be tempted to say: “That's it. I'm not buying you another cell phone until you're in college,” but that is unlikely to be the most educational solution. The time frame should be measured in days or weeks, not in months or years. If consequences are too severe, kids tend to write their parents off completely and feel they have been written off.
Instead, the parents should give the teen a clear path to re-earning the privilege, negotiating the terms. Maybe he has to contribute 80% of his allowance and do some extra chores until the phone is paid for. Showing that they're reasonable and willing to negotiate is a model of adult behavior, and it's also their key to success.
The older the child, the more important it is to negotiate what the rules are to be, and also what exceptions there might be. It's fine if there's a general rule that they can't stay out after 11 o'clock. But if a special event comes along that starts at 10 o'clock and won't end until 2 a.m., it's best to be flexible about the curfew this one time. When teens and parents negotiate one-time exceptions as needed, there is structure but rebellion or sneaking is not brought out.
Negotiation is important. A 30-year longitudinal study from the University of California, Berkeley, demonstrated that parents who managed to negotiate the rules with their children had more harmonious relationships with them later (New Dir. Child Adolesc. Dev. 2005;108:61–9). Often a dynamic arises in families where the parents are so generally annoyed with their teen that they reflexively answer, “No!” to any request. That can be really counterproductive when it comes to parenting adolescents. The first response should be: “Yes, if at all possible. Let's talk about it.”
I recommend that parents explicitly discuss the request using the following six points in deciding with the adolescent on their request. Posting these on the refrigerator and making discussing them a routine lets the teen know they are being taken seriously, slows the reflex to say “no,” and may help install them as a mantra in the teen's brain for future decision making:
Six Guides for Decision Making
1. Is it safe?
2. Is it legal?
3. Does it conflict with responsibilities?
4. Does it meet a developmental need?
5. Does it interfere with others?
6. Could it harm his/her development?
Anyone who's read “The Catcher in the Rye” (New York: Little, Brown and Co., 1951) by J.D. Salinger knows that teenagers are especially sensitive to hypocrisy. Parents often talk about the importance of being a moral person, but the teen is aware that they're cheating on their income taxes. They will reject their parents' moral code if they see them being hypocritical.
Clearly, the best way for the parent to encourage their offspring to uphold good moral standards is to actually live those standards 24/7. But almost everyone fails to live up to those standards from time to time, and if they're parents of an adolescent, the teen is sure to be right there when they do. Adolescents appreciate and learn from honesty when that happens. The parent could admit, “Yes, I know I said that you should never curse another driver, but I was so angry that I forgot my own rule.”
In these days of one- and two-child families, where parents often depend on their own children for friendship and companionship, it can be especially devastating to hear a teen say: “I hate you. You're the worst parents ever.” When that happens—and it's almost certain to happen, since it's the rare child who never utters such a sentiment—the parent's best response is not to rise to the bait of an angry teenager. They don't really mean it. And if the parent shows too much visible distress, or starts to punish them for saying those things, there won't be as much opportunity to recover. A simple “I am sorry you feel that way right now. I can see that you are really angry about [my decision, your curfew, what I said].”
And when the teen notices that the parent has not reacted to such provocation, that in itself is a valuable life lesson. The next time a street tough tosses off an insult, he'll be more likely to simply shrug his shoulders and walk away. For additional information on dealing with adolescents, the American Academy of Pediatrics maintains a particularly good collection of resources for parents at www.healthychildren.org
www.CHADIS.com[email protected]
Adolescents are often the most intimidating of our patients. Let's face it: Most of us chose pediatrics because we like little kids. If a 15-minute office visit with a sullen teenager can be so difficult, imagine living with one 24/7. Actually, many of us won't have to imagine—we ourselves are the parents of adolescents, and we know just how challenging that can be.
Despite our own feelings of inadequacy, we can help parents make the transition from raising the innocent younger child to guiding the testy teen into adulthood. A failure to make that transition in parenting style can contribute greatly to a suboptimal outcome.
But your guidance needs to start early. When a parent comes into the office demanding that you administer a drug test or a pregnancy test, you have probably missed the window for effective action. The horse is well out of the barn.
The time to start is earlier—much earlier. All of parenting involves the balancing act between supporting dependency and promoting independence. When people first become parents, they are consumed with accepting the huge dependency of their baby. As the child gets older, parents must allow the child more independence for things to go smoothly.
But adolescence is a time when that balancing act requires truly skilled acrobatics. Teens and their parents need to negotiate the “Four I's” of adolescent development: Initiative, Individuation, Independence, and Intimacy.
Adolescents clearly need to take the initiative in their activities, including when they do their chores and how they manage homework. If parents get in the way and try to structure all of that, they're going to get a lot of pushback.
In terms of individuation—discovering who they are—teenagers are highly sensitive to the standards of peers. They're more interested in what their peers think they should do than what their parents think they should do. On one level, this includes how many ear piercings they have and how they dress. But on a broader level, they need to think their parents are wrong about most things in order to feel “like their own person.” Offering an opinion can be beneficial in giving the adolescent something to counter, but ideally save consequences for more substantial failings. In terms of independence, teenagers are better educated by learning from the consequences of their own actions when those actions are not harmful to their futures.
And in terms of intimacy, teens want and need privacy for their budding relationships. Parents need to learn how to be available to talk about relationships, but not ask too many questions.
Different teens move through these changes at different times. And on top of that, the transition may not always go in one direction. A teen may want to be very independent in choosing her clothes. But the same teen may want a lot of parental help on getting her homework done and on handling peer situations. That's part of what makes parenting adolescents so difficult.
Parents need to gradually release control and let their teens exert more independence. But the key word in that sentence is “gradually,” and parents need to be alert for signs that the child is not ready or has not yet earned that freedom.
Let's say the parents have allowed their 13-year-old to have a cell phone. Let's say that a few weeks later, the child hurls the phone against the wall in anger, shattering it beyond repair. Some parents might be tempted to say: “That's it. I'm not buying you another cell phone until you're in college,” but that is unlikely to be the most educational solution. The time frame should be measured in days or weeks, not in months or years. If consequences are too severe, kids tend to write their parents off completely and feel they have been written off.
Instead, the parents should give the teen a clear path to re-earning the privilege, negotiating the terms. Maybe he has to contribute 80% of his allowance and do some extra chores until the phone is paid for. Showing that they're reasonable and willing to negotiate is a model of adult behavior, and it's also their key to success.
The older the child, the more important it is to negotiate what the rules are to be, and also what exceptions there might be. It's fine if there's a general rule that they can't stay out after 11 o'clock. But if a special event comes along that starts at 10 o'clock and won't end until 2 a.m., it's best to be flexible about the curfew this one time. When teens and parents negotiate one-time exceptions as needed, there is structure but rebellion or sneaking is not brought out.
Negotiation is important. A 30-year longitudinal study from the University of California, Berkeley, demonstrated that parents who managed to negotiate the rules with their children had more harmonious relationships with them later (New Dir. Child Adolesc. Dev. 2005;108:61–9). Often a dynamic arises in families where the parents are so generally annoyed with their teen that they reflexively answer, “No!” to any request. That can be really counterproductive when it comes to parenting adolescents. The first response should be: “Yes, if at all possible. Let's talk about it.”
I recommend that parents explicitly discuss the request using the following six points in deciding with the adolescent on their request. Posting these on the refrigerator and making discussing them a routine lets the teen know they are being taken seriously, slows the reflex to say “no,” and may help install them as a mantra in the teen's brain for future decision making:
Six Guides for Decision Making
1. Is it safe?
2. Is it legal?
3. Does it conflict with responsibilities?
4. Does it meet a developmental need?
5. Does it interfere with others?
6. Could it harm his/her development?
Anyone who's read “The Catcher in the Rye” (New York: Little, Brown and Co., 1951) by J.D. Salinger knows that teenagers are especially sensitive to hypocrisy. Parents often talk about the importance of being a moral person, but the teen is aware that they're cheating on their income taxes. They will reject their parents' moral code if they see them being hypocritical.
Clearly, the best way for the parent to encourage their offspring to uphold good moral standards is to actually live those standards 24/7. But almost everyone fails to live up to those standards from time to time, and if they're parents of an adolescent, the teen is sure to be right there when they do. Adolescents appreciate and learn from honesty when that happens. The parent could admit, “Yes, I know I said that you should never curse another driver, but I was so angry that I forgot my own rule.”
In these days of one- and two-child families, where parents often depend on their own children for friendship and companionship, it can be especially devastating to hear a teen say: “I hate you. You're the worst parents ever.” When that happens—and it's almost certain to happen, since it's the rare child who never utters such a sentiment—the parent's best response is not to rise to the bait of an angry teenager. They don't really mean it. And if the parent shows too much visible distress, or starts to punish them for saying those things, there won't be as much opportunity to recover. A simple “I am sorry you feel that way right now. I can see that you are really angry about [my decision, your curfew, what I said].”
And when the teen notices that the parent has not reacted to such provocation, that in itself is a valuable life lesson. The next time a street tough tosses off an insult, he'll be more likely to simply shrug his shoulders and walk away. For additional information on dealing with adolescents, the American Academy of Pediatrics maintains a particularly good collection of resources for parents at www.healthychildren.org
Concussion Rates Are Rising in Younger Athletes Aged 8-13 Years
Approximately 40% of emergency department visits for sports-related concussions in young athletes occurred in children aged 8–13 years, based on data from concussion-related ED visits in the United States between 2001 and 2005.
There are two main concerns about sports-related concussion in younger children, compared with college athletes and adults, lead author Dr. Lisa L. Bakhos said in an interview. Dr. Bakhos conducted the study while she was a teaching fellow at Brown University in Providence, R.I. (Pediatrics 2010 Aug. 30 [doi:10.1542/peds.2009–3101]).
"First, many parents, coaches, teachers, and other adults feel that because these athletes are so young, they could not possibly get seriously hurt. As we have seen time and time again, this is, of course, not the case," said Dr. Bakhos, who is currently an emergency physician at the Jersey Shore University Medical Center in Neptune, N.J.
In addition, more data have surfaced about cognitive deficits in older children after concussion, she said, "which leads to conjecture that younger children would suffer the same — if not more — deficits long term."
However, the link between sports-related concussion and cognitive deficits needs further study, she commented.
The American Academy of Pediatrics has just released a new clinical report, "Sport-Related Concussion in Children and Adolescents" to aid in this effort (Pediatrics 2010 Aug. 30 [doi:10.1542/peds. 2010–2005]).
To get a better picture of the scope of sports-related concussion in young athletes, Dr. Bakhos and her colleagues reviewed data from the NEISS (National Electronic Injury Surveillance System) from 1997 through 2007, and from the NEISS-AIP (All-Injury Program) from 2001 through 2005.
The NEISS system allows researchers to investigate injury- and product-related ED visits.
In 2001–2005, approximately half of all ED visits for concussion across older and younger age groups were related to sports, including 58% of visits in children aged 8–13 years and 46% of visits in those aged 14–19 years.
Put another way, approximately 4 in 1,000 children aged 8–13 years and 6 in 1,000 of those aged 14–19 years went to the ED for a sports-related concussion.
During the 10-year period of 1997–2007, ED visits for the most popular organized team sports (football, ice hockey, soccer, basketball, and baseball) doubled in 8- to 13-year-olds and increased by more than 200% in 14- to 19-year-olds.
"The take-home message for pediatricians is, take concussion seriously even in the very young athlete," said Dr. Bakhos. "Children with concussion should be followed just as closely as a child with a sprained ankle or a broken bone. Return-to-play guidelines should be followed closely and stressed to parents."
"We as pediatricians should also stress to parents the importance of concussion prevention in sport as well, mostly [by] the use of helmets at all times," she emphasized.
The study was limited by the exclusion of sports-related concussions that were treated in non-ED settings, and by the underreporting of sports-related concussions by young athletes, their parents, and their coaches, the researchers noted.
But the rise in sports-related concussions in younger and older children suggests the need for more research and guidance in preventing and treating these injuries, they added.
To help clinicians manage sports-related concussions in young athletes, the AAP published a new clinical report that "outlines the current state of knowledge on pediatric and adolescent sport-related concussions," wrote lead authors Dr. Mark E. Halstead and Dr. Kevin D. Walter, on behalf of the AAP's Council on Sports Medicine and Fitness. It includes the SCAT 2 (Sport Concussion Assessment Tool 2), a standardized method of evaluating concussion in athletes aged 10 and older.
The report outlines recommendations regarding sports-related concussion, including the following:
▸ Stay off the field. Even if symptoms subside, young athletes should never return to play on the same day they have a concussion. Younger athletes need more recovery time and a more conservative approach than do college or professional athletes.
▸ See a doctor. Any children or adolescents who suffer concussions during sports should be medically cleared by a physician before they return to activity.
▸ Rest mind and body. All young athletes should refrain from physical activity until they are asymptomatic at rest and when active. Rest includes mental as well as physical rest.
Some evidence suggests that cognitive exertion — including doing homework, watching TV, and playing video games — can exacerbate symptoms post concussion.
In the last few years, several states have passed laws requiring educational materials about sports-related concussion for school-aged athletes, coaches, and parents. The state laws were a consideration, but the AAP began working on the report before the first law was passed, said Dr. Halstead, director of the sports concussion program in the department of orthopedics at Washington University in St. Louis.
"We felt there was a need to address specifically the [pediatric] athlete and address all the recent research that has been published on this topic," he said in an interview.
"The recommendations presented aren't significantly different from other recent documents published, but these were primarily published in sports medicine journals, which many pediatricians do not review.
"We wanted to bring these recommendations to the forefront to the pediatric community, and expand upon the details provided in previous documents published.
"We have highlighted some of the new research on neuroimaging, balance assessments, long-term complications, education, and neuropsychological testing," Dr. Halstead said.
Dr. Walter added, "I think it is also important to recognize that because we have learned more about concussion diagnosis, treatment, and complications, the treatment that coaches and parents received when they had a concussion themselves at a young age is likely different than today."
Many parents and coaches don't think concussion is a big deal because they had one when they were younger and they "toughed it out" and "are fine now," said Dr. Walter, program director of pediatric and adolescent sports medicine at Children's Hospital of Wisconsin in Milwaukee.
The authors acknowledged the lack of published baseline neuropsychological data on children younger than 12 years, and noted that assessment by a neuropsychologist might be helpful for children who have had more than one concussion, or whose postconcussive symptoms persist for several months.
I'm not surprised by the increase in reports of concussions in young athletes. And because not every kid with a concussion goes to the emergency department, there are even more injuries occurring that are not being reported.
I think greater awareness and better diagnosis are the main reasons why the number of sports-related concussions is rising. Until 10 years ago, the medical literature focused only on concussions that involved loss of consciousness. But what we have learned in the past decade is that the subtleties of this injury are absolutely critical for diagnosis.
For example, loss of consciousness is actually less predictive than loss of memory. (I published a paper in 2003 showing that amnesia or memory loss around the time of the concussion is 10 times more predictive than a loss of consciousness.) Changes in the way we define the injury are driving the rise in reported concussions in young athletes.
As we continue to peel the onion on concussion, we realize that it is an extremely complex injury, and that there are more problems in those who are injured—particularly kids. Also, we now have animal models that help show what happens in the brain after a concussion. This knowledge base has accumulated at warp speed over the last 10 years, and with that has come better recognition, better management, and better understanding of the injury, as well as more concern.
Most importantly, neurocognitive testing is becoming more widely used as a way to assess sports-related concussion, and it is the key to why there is so much attention now being paid to the injury: We now have a way to measure it by collecting baseline data. The sensitivity and specificity of such tests are impressive.
One of the keys to improving the management of pediatric concussion is to get knowledge related to this injury, as well as its many assessment tools, into pediatric offices. Clinics are available around the United States to help pediatricians who want to incorporate neurocognitive testing into their practices. The American Academy of Pediatrics' report by Dr. Halstead and Dr. Walter lists several assessment tools, and it includes other valuable, relevant information about managing sports-related concussions in young athletes.
MICHAEL COLLINS, PH.D., is the assistant director of the sports medicine concussion program at the University of Pittsburgh Medical Center. He also coauthored the Centers for Disease Control and Prevention's “Heads Up: Brain Injury in Your Practice” tool kit for physicians.
I'm not surprised by the increase in reports of concussions in young athletes. And because not every kid with a concussion goes to the emergency department, there are even more injuries occurring that are not being reported.
I think greater awareness and better diagnosis are the main reasons why the number of sports-related concussions is rising. Until 10 years ago, the medical literature focused only on concussions that involved loss of consciousness. But what we have learned in the past decade is that the subtleties of this injury are absolutely critical for diagnosis.
For example, loss of consciousness is actually less predictive than loss of memory. (I published a paper in 2003 showing that amnesia or memory loss around the time of the concussion is 10 times more predictive than a loss of consciousness.) Changes in the way we define the injury are driving the rise in reported concussions in young athletes.
As we continue to peel the onion on concussion, we realize that it is an extremely complex injury, and that there are more problems in those who are injured—particularly kids. Also, we now have animal models that help show what happens in the brain after a concussion. This knowledge base has accumulated at warp speed over the last 10 years, and with that has come better recognition, better management, and better understanding of the injury, as well as more concern.
Most importantly, neurocognitive testing is becoming more widely used as a way to assess sports-related concussion, and it is the key to why there is so much attention now being paid to the injury: We now have a way to measure it by collecting baseline data. The sensitivity and specificity of such tests are impressive.
One of the keys to improving the management of pediatric concussion is to get knowledge related to this injury, as well as its many assessment tools, into pediatric offices. Clinics are available around the United States to help pediatricians who want to incorporate neurocognitive testing into their practices. The American Academy of Pediatrics' report by Dr. Halstead and Dr. Walter lists several assessment tools, and it includes other valuable, relevant information about managing sports-related concussions in young athletes.
MICHAEL COLLINS, PH.D., is the assistant director of the sports medicine concussion program at the University of Pittsburgh Medical Center. He also coauthored the Centers for Disease Control and Prevention's “Heads Up: Brain Injury in Your Practice” tool kit for physicians.
I'm not surprised by the increase in reports of concussions in young athletes. And because not every kid with a concussion goes to the emergency department, there are even more injuries occurring that are not being reported.
I think greater awareness and better diagnosis are the main reasons why the number of sports-related concussions is rising. Until 10 years ago, the medical literature focused only on concussions that involved loss of consciousness. But what we have learned in the past decade is that the subtleties of this injury are absolutely critical for diagnosis.
For example, loss of consciousness is actually less predictive than loss of memory. (I published a paper in 2003 showing that amnesia or memory loss around the time of the concussion is 10 times more predictive than a loss of consciousness.) Changes in the way we define the injury are driving the rise in reported concussions in young athletes.
As we continue to peel the onion on concussion, we realize that it is an extremely complex injury, and that there are more problems in those who are injured—particularly kids. Also, we now have animal models that help show what happens in the brain after a concussion. This knowledge base has accumulated at warp speed over the last 10 years, and with that has come better recognition, better management, and better understanding of the injury, as well as more concern.
Most importantly, neurocognitive testing is becoming more widely used as a way to assess sports-related concussion, and it is the key to why there is so much attention now being paid to the injury: We now have a way to measure it by collecting baseline data. The sensitivity and specificity of such tests are impressive.
One of the keys to improving the management of pediatric concussion is to get knowledge related to this injury, as well as its many assessment tools, into pediatric offices. Clinics are available around the United States to help pediatricians who want to incorporate neurocognitive testing into their practices. The American Academy of Pediatrics' report by Dr. Halstead and Dr. Walter lists several assessment tools, and it includes other valuable, relevant information about managing sports-related concussions in young athletes.
MICHAEL COLLINS, PH.D., is the assistant director of the sports medicine concussion program at the University of Pittsburgh Medical Center. He also coauthored the Centers for Disease Control and Prevention's “Heads Up: Brain Injury in Your Practice” tool kit for physicians.
Approximately 40% of emergency department visits for sports-related concussions in young athletes occurred in children aged 8–13 years, based on data from concussion-related ED visits in the United States between 2001 and 2005.
There are two main concerns about sports-related concussion in younger children, compared with college athletes and adults, lead author Dr. Lisa L. Bakhos said in an interview. Dr. Bakhos conducted the study while she was a teaching fellow at Brown University in Providence, R.I. (Pediatrics 2010 Aug. 30 [doi:10.1542/peds.2009–3101]).
"First, many parents, coaches, teachers, and other adults feel that because these athletes are so young, they could not possibly get seriously hurt. As we have seen time and time again, this is, of course, not the case," said Dr. Bakhos, who is currently an emergency physician at the Jersey Shore University Medical Center in Neptune, N.J.
In addition, more data have surfaced about cognitive deficits in older children after concussion, she said, "which leads to conjecture that younger children would suffer the same — if not more — deficits long term."
However, the link between sports-related concussion and cognitive deficits needs further study, she commented.
The American Academy of Pediatrics has just released a new clinical report, "Sport-Related Concussion in Children and Adolescents" to aid in this effort (Pediatrics 2010 Aug. 30 [doi:10.1542/peds. 2010–2005]).
To get a better picture of the scope of sports-related concussion in young athletes, Dr. Bakhos and her colleagues reviewed data from the NEISS (National Electronic Injury Surveillance System) from 1997 through 2007, and from the NEISS-AIP (All-Injury Program) from 2001 through 2005.
The NEISS system allows researchers to investigate injury- and product-related ED visits.
In 2001–2005, approximately half of all ED visits for concussion across older and younger age groups were related to sports, including 58% of visits in children aged 8–13 years and 46% of visits in those aged 14–19 years.
Put another way, approximately 4 in 1,000 children aged 8–13 years and 6 in 1,000 of those aged 14–19 years went to the ED for a sports-related concussion.
During the 10-year period of 1997–2007, ED visits for the most popular organized team sports (football, ice hockey, soccer, basketball, and baseball) doubled in 8- to 13-year-olds and increased by more than 200% in 14- to 19-year-olds.
"The take-home message for pediatricians is, take concussion seriously even in the very young athlete," said Dr. Bakhos. "Children with concussion should be followed just as closely as a child with a sprained ankle or a broken bone. Return-to-play guidelines should be followed closely and stressed to parents."
"We as pediatricians should also stress to parents the importance of concussion prevention in sport as well, mostly [by] the use of helmets at all times," she emphasized.
The study was limited by the exclusion of sports-related concussions that were treated in non-ED settings, and by the underreporting of sports-related concussions by young athletes, their parents, and their coaches, the researchers noted.
But the rise in sports-related concussions in younger and older children suggests the need for more research and guidance in preventing and treating these injuries, they added.
To help clinicians manage sports-related concussions in young athletes, the AAP published a new clinical report that "outlines the current state of knowledge on pediatric and adolescent sport-related concussions," wrote lead authors Dr. Mark E. Halstead and Dr. Kevin D. Walter, on behalf of the AAP's Council on Sports Medicine and Fitness. It includes the SCAT 2 (Sport Concussion Assessment Tool 2), a standardized method of evaluating concussion in athletes aged 10 and older.
The report outlines recommendations regarding sports-related concussion, including the following:
▸ Stay off the field. Even if symptoms subside, young athletes should never return to play on the same day they have a concussion. Younger athletes need more recovery time and a more conservative approach than do college or professional athletes.
▸ See a doctor. Any children or adolescents who suffer concussions during sports should be medically cleared by a physician before they return to activity.
▸ Rest mind and body. All young athletes should refrain from physical activity until they are asymptomatic at rest and when active. Rest includes mental as well as physical rest.
Some evidence suggests that cognitive exertion — including doing homework, watching TV, and playing video games — can exacerbate symptoms post concussion.
In the last few years, several states have passed laws requiring educational materials about sports-related concussion for school-aged athletes, coaches, and parents. The state laws were a consideration, but the AAP began working on the report before the first law was passed, said Dr. Halstead, director of the sports concussion program in the department of orthopedics at Washington University in St. Louis.
"We felt there was a need to address specifically the [pediatric] athlete and address all the recent research that has been published on this topic," he said in an interview.
"The recommendations presented aren't significantly different from other recent documents published, but these were primarily published in sports medicine journals, which many pediatricians do not review.
"We wanted to bring these recommendations to the forefront to the pediatric community, and expand upon the details provided in previous documents published.
"We have highlighted some of the new research on neuroimaging, balance assessments, long-term complications, education, and neuropsychological testing," Dr. Halstead said.
Dr. Walter added, "I think it is also important to recognize that because we have learned more about concussion diagnosis, treatment, and complications, the treatment that coaches and parents received when they had a concussion themselves at a young age is likely different than today."
Many parents and coaches don't think concussion is a big deal because they had one when they were younger and they "toughed it out" and "are fine now," said Dr. Walter, program director of pediatric and adolescent sports medicine at Children's Hospital of Wisconsin in Milwaukee.
The authors acknowledged the lack of published baseline neuropsychological data on children younger than 12 years, and noted that assessment by a neuropsychologist might be helpful for children who have had more than one concussion, or whose postconcussive symptoms persist for several months.
Approximately 40% of emergency department visits for sports-related concussions in young athletes occurred in children aged 8–13 years, based on data from concussion-related ED visits in the United States between 2001 and 2005.
There are two main concerns about sports-related concussion in younger children, compared with college athletes and adults, lead author Dr. Lisa L. Bakhos said in an interview. Dr. Bakhos conducted the study while she was a teaching fellow at Brown University in Providence, R.I. (Pediatrics 2010 Aug. 30 [doi:10.1542/peds.2009–3101]).
"First, many parents, coaches, teachers, and other adults feel that because these athletes are so young, they could not possibly get seriously hurt. As we have seen time and time again, this is, of course, not the case," said Dr. Bakhos, who is currently an emergency physician at the Jersey Shore University Medical Center in Neptune, N.J.
In addition, more data have surfaced about cognitive deficits in older children after concussion, she said, "which leads to conjecture that younger children would suffer the same — if not more — deficits long term."
However, the link between sports-related concussion and cognitive deficits needs further study, she commented.
The American Academy of Pediatrics has just released a new clinical report, "Sport-Related Concussion in Children and Adolescents" to aid in this effort (Pediatrics 2010 Aug. 30 [doi:10.1542/peds. 2010–2005]).
To get a better picture of the scope of sports-related concussion in young athletes, Dr. Bakhos and her colleagues reviewed data from the NEISS (National Electronic Injury Surveillance System) from 1997 through 2007, and from the NEISS-AIP (All-Injury Program) from 2001 through 2005.
The NEISS system allows researchers to investigate injury- and product-related ED visits.
In 2001–2005, approximately half of all ED visits for concussion across older and younger age groups were related to sports, including 58% of visits in children aged 8–13 years and 46% of visits in those aged 14–19 years.
Put another way, approximately 4 in 1,000 children aged 8–13 years and 6 in 1,000 of those aged 14–19 years went to the ED for a sports-related concussion.
During the 10-year period of 1997–2007, ED visits for the most popular organized team sports (football, ice hockey, soccer, basketball, and baseball) doubled in 8- to 13-year-olds and increased by more than 200% in 14- to 19-year-olds.
"The take-home message for pediatricians is, take concussion seriously even in the very young athlete," said Dr. Bakhos. "Children with concussion should be followed just as closely as a child with a sprained ankle or a broken bone. Return-to-play guidelines should be followed closely and stressed to parents."
"We as pediatricians should also stress to parents the importance of concussion prevention in sport as well, mostly [by] the use of helmets at all times," she emphasized.
The study was limited by the exclusion of sports-related concussions that were treated in non-ED settings, and by the underreporting of sports-related concussions by young athletes, their parents, and their coaches, the researchers noted.
But the rise in sports-related concussions in younger and older children suggests the need for more research and guidance in preventing and treating these injuries, they added.
To help clinicians manage sports-related concussions in young athletes, the AAP published a new clinical report that "outlines the current state of knowledge on pediatric and adolescent sport-related concussions," wrote lead authors Dr. Mark E. Halstead and Dr. Kevin D. Walter, on behalf of the AAP's Council on Sports Medicine and Fitness. It includes the SCAT 2 (Sport Concussion Assessment Tool 2), a standardized method of evaluating concussion in athletes aged 10 and older.
The report outlines recommendations regarding sports-related concussion, including the following:
▸ Stay off the field. Even if symptoms subside, young athletes should never return to play on the same day they have a concussion. Younger athletes need more recovery time and a more conservative approach than do college or professional athletes.
▸ See a doctor. Any children or adolescents who suffer concussions during sports should be medically cleared by a physician before they return to activity.
▸ Rest mind and body. All young athletes should refrain from physical activity until they are asymptomatic at rest and when active. Rest includes mental as well as physical rest.
Some evidence suggests that cognitive exertion — including doing homework, watching TV, and playing video games — can exacerbate symptoms post concussion.
In the last few years, several states have passed laws requiring educational materials about sports-related concussion for school-aged athletes, coaches, and parents. The state laws were a consideration, but the AAP began working on the report before the first law was passed, said Dr. Halstead, director of the sports concussion program in the department of orthopedics at Washington University in St. Louis.
"We felt there was a need to address specifically the [pediatric] athlete and address all the recent research that has been published on this topic," he said in an interview.
"The recommendations presented aren't significantly different from other recent documents published, but these were primarily published in sports medicine journals, which many pediatricians do not review.
"We wanted to bring these recommendations to the forefront to the pediatric community, and expand upon the details provided in previous documents published.
"We have highlighted some of the new research on neuroimaging, balance assessments, long-term complications, education, and neuropsychological testing," Dr. Halstead said.
Dr. Walter added, "I think it is also important to recognize that because we have learned more about concussion diagnosis, treatment, and complications, the treatment that coaches and parents received when they had a concussion themselves at a young age is likely different than today."
Many parents and coaches don't think concussion is a big deal because they had one when they were younger and they "toughed it out" and "are fine now," said Dr. Walter, program director of pediatric and adolescent sports medicine at Children's Hospital of Wisconsin in Milwaukee.
The authors acknowledged the lack of published baseline neuropsychological data on children younger than 12 years, and noted that assessment by a neuropsychologist might be helpful for children who have had more than one concussion, or whose postconcussive symptoms persist for several months.
Aggressive Negotiations
Hospitalists are in position to take a leading role in the prevention of catheter-related bloodstream infections (CRBSIs), according to a spokeswoman for the Association for Professionals in Infection Control and Epidemiology (APIC).
The APIC perspective is timely, as the group released a survey this summer that found hospitals continue to struggle with preventable hospital-associated infections (HAIs). Half the survey respondents said their institutions struggle with CRBSIs and blame lack of time, resources, and a lack of administrative initiative as “hindering their ability to combat these infections more aggressively.”
The push also comes as a new Centers for Medicare and Medicaid Services rule means that, beginning next year, central-line-associated bloodstream infections (CLABSIs) will be reported and posted on a CDC website. The public disclosure of such preventable infections should motivate physicians to more aggressively address the problem, according to the APIC.
“Hospitalists need to be the champions,” says Sharon Jacobs, RN, MS, CIC, manager of infection prevention and control at St. Clair Hospital in Pittsburgh.
To that end, Jacobs offers some tips on how hospitalists and others can help stem the tide of the estimated 80,000 patients a year who develop CRBSIs. They include:
- Hand hygiene: The use of gloves during procedures does not mean physicians should forgo washing their hands.
- Large drapes: Most vendors now include drapes in their line kits, but for those that might not, consider using the largest drape available to cover and protect as much of the patient as possible. Consider creating a cart to store all applicable equipment.
- Focus on care continuum: Insertion of a line is the first step. Make sure the line is properly maintained as long as it remains in the patient. Consider replacing lines hastily inserted in the ED or other departments. Remove all lines as quickly as clinically efficient.
Another key, Jacobs says, is to create a collaborative environment where hospitalists, intensivists, nurses, and others will feel encouraged to point out improvements instead of feeling chastised for pointing out potential errors.
“The mindset is changing,” she adds. “It doesn’t take any longer to follow these procedures than it does to put a line in without them.”
Hospitalists are in position to take a leading role in the prevention of catheter-related bloodstream infections (CRBSIs), according to a spokeswoman for the Association for Professionals in Infection Control and Epidemiology (APIC).
The APIC perspective is timely, as the group released a survey this summer that found hospitals continue to struggle with preventable hospital-associated infections (HAIs). Half the survey respondents said their institutions struggle with CRBSIs and blame lack of time, resources, and a lack of administrative initiative as “hindering their ability to combat these infections more aggressively.”
The push also comes as a new Centers for Medicare and Medicaid Services rule means that, beginning next year, central-line-associated bloodstream infections (CLABSIs) will be reported and posted on a CDC website. The public disclosure of such preventable infections should motivate physicians to more aggressively address the problem, according to the APIC.
“Hospitalists need to be the champions,” says Sharon Jacobs, RN, MS, CIC, manager of infection prevention and control at St. Clair Hospital in Pittsburgh.
To that end, Jacobs offers some tips on how hospitalists and others can help stem the tide of the estimated 80,000 patients a year who develop CRBSIs. They include:
- Hand hygiene: The use of gloves during procedures does not mean physicians should forgo washing their hands.
- Large drapes: Most vendors now include drapes in their line kits, but for those that might not, consider using the largest drape available to cover and protect as much of the patient as possible. Consider creating a cart to store all applicable equipment.
- Focus on care continuum: Insertion of a line is the first step. Make sure the line is properly maintained as long as it remains in the patient. Consider replacing lines hastily inserted in the ED or other departments. Remove all lines as quickly as clinically efficient.
Another key, Jacobs says, is to create a collaborative environment where hospitalists, intensivists, nurses, and others will feel encouraged to point out improvements instead of feeling chastised for pointing out potential errors.
“The mindset is changing,” she adds. “It doesn’t take any longer to follow these procedures than it does to put a line in without them.”
Hospitalists are in position to take a leading role in the prevention of catheter-related bloodstream infections (CRBSIs), according to a spokeswoman for the Association for Professionals in Infection Control and Epidemiology (APIC).
The APIC perspective is timely, as the group released a survey this summer that found hospitals continue to struggle with preventable hospital-associated infections (HAIs). Half the survey respondents said their institutions struggle with CRBSIs and blame lack of time, resources, and a lack of administrative initiative as “hindering their ability to combat these infections more aggressively.”
The push also comes as a new Centers for Medicare and Medicaid Services rule means that, beginning next year, central-line-associated bloodstream infections (CLABSIs) will be reported and posted on a CDC website. The public disclosure of such preventable infections should motivate physicians to more aggressively address the problem, according to the APIC.
“Hospitalists need to be the champions,” says Sharon Jacobs, RN, MS, CIC, manager of infection prevention and control at St. Clair Hospital in Pittsburgh.
To that end, Jacobs offers some tips on how hospitalists and others can help stem the tide of the estimated 80,000 patients a year who develop CRBSIs. They include:
- Hand hygiene: The use of gloves during procedures does not mean physicians should forgo washing their hands.
- Large drapes: Most vendors now include drapes in their line kits, but for those that might not, consider using the largest drape available to cover and protect as much of the patient as possible. Consider creating a cart to store all applicable equipment.
- Focus on care continuum: Insertion of a line is the first step. Make sure the line is properly maintained as long as it remains in the patient. Consider replacing lines hastily inserted in the ED or other departments. Remove all lines as quickly as clinically efficient.
Another key, Jacobs says, is to create a collaborative environment where hospitalists, intensivists, nurses, and others will feel encouraged to point out improvements instead of feeling chastised for pointing out potential errors.
“The mindset is changing,” she adds. “It doesn’t take any longer to follow these procedures than it does to put a line in without them.”
In the Literature: Research You Need to Know
Clinical question: Is there a clinical benefit to continuing dual antiplatelet therapy for more than 12 months after drug-eluting stent placement?
Background: Current guidelines recommend dual antiplatelet therapy for at least 12 months after the placement of a drug-eluting stent. However, no randomized trials have addressed the effects of dual therapy beyond 12 months.
Study design: Randomized, open-label trial.
Setting: Twenty-two cardiac centers in South Korea.
Synopsis: Investigators looked at 2,701 patients, all of whom had undergone drug-eluting stent placement followed by dual therapy with aspirin and clopidogrel for at least 12 months with no major cardiac, cerebrovascular, or bleeding events during that time. Patients were randomized to continue aspirin plus clopidogrel or aspirin alone. The median therapy was 19 months.
Dual therapy led to no significant difference in the primary outcome of myocardial infarction or death from cardiac causes compared with aspirin alone (1.8% vs. 1.2%), nor in any secondary outcomes.
This study has several limitations, including an open-label design. An unexpectedly low event rate dilutes the power of the study to detect clinically important treatment effects.
Bottom line: This study showed no benefit to continuing clopidogrel for more than 12 months after drug-eluting stent placement in addition to aspirin; however, it was significantly underpowered.
Citation: Park SJ, Park DW, Kim YH, et al. Duration of dual antiplatelet therapy after implantation of drug-eluting stents. N Engl J Med. 2010;362(15):1374-1382.
Reviewed for TH eWire by Robert Chang, MD, Anita Hart, MD, Hae-won Kim, MD, Robert Paretti, MD, Helena Pasieka, MD, and Matt Smitherman, MD, University of Michigan, Ann Arbor.
For more physician reviews of HM-related research, visit our website.
Clinical question: Is there a clinical benefit to continuing dual antiplatelet therapy for more than 12 months after drug-eluting stent placement?
Background: Current guidelines recommend dual antiplatelet therapy for at least 12 months after the placement of a drug-eluting stent. However, no randomized trials have addressed the effects of dual therapy beyond 12 months.
Study design: Randomized, open-label trial.
Setting: Twenty-two cardiac centers in South Korea.
Synopsis: Investigators looked at 2,701 patients, all of whom had undergone drug-eluting stent placement followed by dual therapy with aspirin and clopidogrel for at least 12 months with no major cardiac, cerebrovascular, or bleeding events during that time. Patients were randomized to continue aspirin plus clopidogrel or aspirin alone. The median therapy was 19 months.
Dual therapy led to no significant difference in the primary outcome of myocardial infarction or death from cardiac causes compared with aspirin alone (1.8% vs. 1.2%), nor in any secondary outcomes.
This study has several limitations, including an open-label design. An unexpectedly low event rate dilutes the power of the study to detect clinically important treatment effects.
Bottom line: This study showed no benefit to continuing clopidogrel for more than 12 months after drug-eluting stent placement in addition to aspirin; however, it was significantly underpowered.
Citation: Park SJ, Park DW, Kim YH, et al. Duration of dual antiplatelet therapy after implantation of drug-eluting stents. N Engl J Med. 2010;362(15):1374-1382.
Reviewed for TH eWire by Robert Chang, MD, Anita Hart, MD, Hae-won Kim, MD, Robert Paretti, MD, Helena Pasieka, MD, and Matt Smitherman, MD, University of Michigan, Ann Arbor.
For more physician reviews of HM-related research, visit our website.
Clinical question: Is there a clinical benefit to continuing dual antiplatelet therapy for more than 12 months after drug-eluting stent placement?
Background: Current guidelines recommend dual antiplatelet therapy for at least 12 months after the placement of a drug-eluting stent. However, no randomized trials have addressed the effects of dual therapy beyond 12 months.
Study design: Randomized, open-label trial.
Setting: Twenty-two cardiac centers in South Korea.
Synopsis: Investigators looked at 2,701 patients, all of whom had undergone drug-eluting stent placement followed by dual therapy with aspirin and clopidogrel for at least 12 months with no major cardiac, cerebrovascular, or bleeding events during that time. Patients were randomized to continue aspirin plus clopidogrel or aspirin alone. The median therapy was 19 months.
Dual therapy led to no significant difference in the primary outcome of myocardial infarction or death from cardiac causes compared with aspirin alone (1.8% vs. 1.2%), nor in any secondary outcomes.
This study has several limitations, including an open-label design. An unexpectedly low event rate dilutes the power of the study to detect clinically important treatment effects.
Bottom line: This study showed no benefit to continuing clopidogrel for more than 12 months after drug-eluting stent placement in addition to aspirin; however, it was significantly underpowered.
Citation: Park SJ, Park DW, Kim YH, et al. Duration of dual antiplatelet therapy after implantation of drug-eluting stents. N Engl J Med. 2010;362(15):1374-1382.
Reviewed for TH eWire by Robert Chang, MD, Anita Hart, MD, Hae-won Kim, MD, Robert Paretti, MD, Helena Pasieka, MD, and Matt Smitherman, MD, University of Michigan, Ann Arbor.
For more physician reviews of HM-related research, visit our website.
Short Title/Panesar
After another round of epinephrine, I started chest compressionsagain. Warm sweat seeped down my neck and back. In just 10 minutes, the 24‐bed pediatric intensive care unit (PICU) had become much smaller and more confined. Everyone funneled into this one room, this one bed. Beyond it was a blur of color and sound. I forced my strength onto Ricky, my 17‐year‐old patient with muscular dystrophy and end‐stage heart failure. He was admitted 1 week ago with respiratory distress, and he had only gotten worse since then.
Ricky's body, now cool and pale, was a blob of relaxed skin and loose bone beneath me. I straightened my arms, jutted the heel of my left hand over my right and pushed onto his chest. I pushed hard and fast, like I was taught; a dumb robotic motion again and again, trying to keep good position and form. I stared up at the monitor between every few compressions, looking at all the waveforms, anticipating, as if something on the screen was going to pop up suddenly and say EVERYTHING IS GOING TO BE OKAY. But it didn't.
I glanced beyond the bedside. There was a flurry of people bumping each other, asking for things, telling things, giving and receiving things. All of them were moving, but really had no place to go. This was the place. And in the far corner of the room, stood Mom and Dad.
In between the sink and recliner chair filled with clothes and books, they were the only people that stood still. Swollen feet planted in white socks. Their shoulders sagged.
I love you, I love you, Ricky. No, no, no. Mom and Dad kept on saying between sobs. I wondered if he could hear them. I wished he could hear them. Then I wished they would stop saying anything at all. I felt a rib give under my hands.
From the corner of my left eye, I saw Dad holding Mom upright by the wall. She wore red‐rimmed eyes and wet cheeks and took puttering breaths. Dad squeezed tissues in his hand, then into his eyes and nose and then back into his fist. They kept saying the words over and over, like they knew no other. I pushed harder and faster, but he didn't turn any pinker. Damn it. Damn it. There was plenty of noise, but above it all, I heard their voices. When I was told to hold compressions to check for a pulse, I stood still with my hands at my sides. I felt unnecessary. My precious little contribution to the commotion interrupted.
We all looked up at the monitor.
Stop, please stop. That's it, dad said, somewhere in the infinite pause. Mom still mumbled no over and over again. I turned to her and listened. I watched her pursed mouth and I imagined what it was Dad felt as he held her. Her body shook a Morse code into him, telling him it was time to give up. That it was over. That she couldn't take watching me pound away on her son's chest anymore. That it was okay to let Ricky rest. All the words that she couldn't find, or have the coordination to say, Dad translated for her.
He held her with a desperate grip, for a few moments longer. Maybe, the harder he squeezed, the more life he could push out of her, out of himself, and that effervescent pulse would find its way to their son's heart. But maybe all he could sense was her quiet internal whisper. And they told us again, as I remembered, just like all the soft conversations we had before in the back of the room, while Ricky slept, sedated on narcotics.
I put my fingers over his radial artery and closed my eyes.
Don't let Ricky feel pain, she said. It was the day we intubated him, only hours after he had been admitted.
Do what you can do, just don't Dad trailed off. He stared up at the ceiling and sighed. We listened to the gasp and hiss of the ventilator for a few more moments in silence.
We can try what you say, but no pain. We should know when to quitfor Ricky. Okay? Mom said, waiting for the tears as her nose moistened. She stared up at me.
Okay, I said. I nodded and stared back.
Dad squeezed her arm again, wrapped his around hers and massaged her. She had started to shake.
No pulse. I opened my eyes.
I stared at Ricky's face. His eyelids were half open, his lips were blue. No change on the monitor. I motioned to start compressions again.
Okay, Dad said.
Okay, stop! He's had enough. His dry lips and wet face moved and voiced the end. The room froze.
My muscles relaxed and I splayed my fingers wide, my way of showing that I was letting up. I watched myself lean back, unbelieving, and looked at the screen again. The rhythm drifted from pulseless electrical activity to asystole.
Mom and Dad simultaneously shut their eyes as if they saw something that we didn't and couldn't bear to see anymore. They opened them, looked at Ricky and slowly, as everyone stared, moved to the foot of the bed and began to rub his bare feet.
In subtle efficiency, the room was transformed. We turned off the monitors, we pushed out the carts and equipment, we picked up after ourselves, we dimmed the lights, we pulled the curtains and we left Mom and Dad with their son. Slow, deliberate whispers and motion now, it sounded empty without the background of rhythmic mechanical sounds. No dings, bleeps or rings; no pistons, suctions or pumps; only the occasional sound of tissue being ripped out of a box.
We sat with the family an hour later, in the conference room, to sign papers, for autopsy, for death certificates, for funeral preparations. Mom and Dad didn't know how to answer, and they drifted together to consider how they wanted Ricky's body cared for. Burial? Cremation?
I don't know, Mom said as she tried to fold the shredded tissues in her hand. He had a spinal rod placed his back years ago for his scoliosis. A titanium rod in his spine. Would that even burn? she asked.
We stared at each other, confused and unknowing.
We never thought of that, she said. She began to think out loud. If he were cremated, I don't think I'd want his spinal rod as a reminder. She cocked her head back. What a weird keepsake! She laughed, Where would I keep it? Above the fireplace? How odd. She rolled her eyes, and started to cry again.
After another round of epinephrine, I started chest compressionsagain. Warm sweat seeped down my neck and back. In just 10 minutes, the 24‐bed pediatric intensive care unit (PICU) had become much smaller and more confined. Everyone funneled into this one room, this one bed. Beyond it was a blur of color and sound. I forced my strength onto Ricky, my 17‐year‐old patient with muscular dystrophy and end‐stage heart failure. He was admitted 1 week ago with respiratory distress, and he had only gotten worse since then.
Ricky's body, now cool and pale, was a blob of relaxed skin and loose bone beneath me. I straightened my arms, jutted the heel of my left hand over my right and pushed onto his chest. I pushed hard and fast, like I was taught; a dumb robotic motion again and again, trying to keep good position and form. I stared up at the monitor between every few compressions, looking at all the waveforms, anticipating, as if something on the screen was going to pop up suddenly and say EVERYTHING IS GOING TO BE OKAY. But it didn't.
I glanced beyond the bedside. There was a flurry of people bumping each other, asking for things, telling things, giving and receiving things. All of them were moving, but really had no place to go. This was the place. And in the far corner of the room, stood Mom and Dad.
In between the sink and recliner chair filled with clothes and books, they were the only people that stood still. Swollen feet planted in white socks. Their shoulders sagged.
I love you, I love you, Ricky. No, no, no. Mom and Dad kept on saying between sobs. I wondered if he could hear them. I wished he could hear them. Then I wished they would stop saying anything at all. I felt a rib give under my hands.
From the corner of my left eye, I saw Dad holding Mom upright by the wall. She wore red‐rimmed eyes and wet cheeks and took puttering breaths. Dad squeezed tissues in his hand, then into his eyes and nose and then back into his fist. They kept saying the words over and over, like they knew no other. I pushed harder and faster, but he didn't turn any pinker. Damn it. Damn it. There was plenty of noise, but above it all, I heard their voices. When I was told to hold compressions to check for a pulse, I stood still with my hands at my sides. I felt unnecessary. My precious little contribution to the commotion interrupted.
We all looked up at the monitor.
Stop, please stop. That's it, dad said, somewhere in the infinite pause. Mom still mumbled no over and over again. I turned to her and listened. I watched her pursed mouth and I imagined what it was Dad felt as he held her. Her body shook a Morse code into him, telling him it was time to give up. That it was over. That she couldn't take watching me pound away on her son's chest anymore. That it was okay to let Ricky rest. All the words that she couldn't find, or have the coordination to say, Dad translated for her.
He held her with a desperate grip, for a few moments longer. Maybe, the harder he squeezed, the more life he could push out of her, out of himself, and that effervescent pulse would find its way to their son's heart. But maybe all he could sense was her quiet internal whisper. And they told us again, as I remembered, just like all the soft conversations we had before in the back of the room, while Ricky slept, sedated on narcotics.
I put my fingers over his radial artery and closed my eyes.
Don't let Ricky feel pain, she said. It was the day we intubated him, only hours after he had been admitted.
Do what you can do, just don't Dad trailed off. He stared up at the ceiling and sighed. We listened to the gasp and hiss of the ventilator for a few more moments in silence.
We can try what you say, but no pain. We should know when to quitfor Ricky. Okay? Mom said, waiting for the tears as her nose moistened. She stared up at me.
Okay, I said. I nodded and stared back.
Dad squeezed her arm again, wrapped his around hers and massaged her. She had started to shake.
No pulse. I opened my eyes.
I stared at Ricky's face. His eyelids were half open, his lips were blue. No change on the monitor. I motioned to start compressions again.
Okay, Dad said.
Okay, stop! He's had enough. His dry lips and wet face moved and voiced the end. The room froze.
My muscles relaxed and I splayed my fingers wide, my way of showing that I was letting up. I watched myself lean back, unbelieving, and looked at the screen again. The rhythm drifted from pulseless electrical activity to asystole.
Mom and Dad simultaneously shut their eyes as if they saw something that we didn't and couldn't bear to see anymore. They opened them, looked at Ricky and slowly, as everyone stared, moved to the foot of the bed and began to rub his bare feet.
In subtle efficiency, the room was transformed. We turned off the monitors, we pushed out the carts and equipment, we picked up after ourselves, we dimmed the lights, we pulled the curtains and we left Mom and Dad with their son. Slow, deliberate whispers and motion now, it sounded empty without the background of rhythmic mechanical sounds. No dings, bleeps or rings; no pistons, suctions or pumps; only the occasional sound of tissue being ripped out of a box.
We sat with the family an hour later, in the conference room, to sign papers, for autopsy, for death certificates, for funeral preparations. Mom and Dad didn't know how to answer, and they drifted together to consider how they wanted Ricky's body cared for. Burial? Cremation?
I don't know, Mom said as she tried to fold the shredded tissues in her hand. He had a spinal rod placed his back years ago for his scoliosis. A titanium rod in his spine. Would that even burn? she asked.
We stared at each other, confused and unknowing.
We never thought of that, she said. She began to think out loud. If he were cremated, I don't think I'd want his spinal rod as a reminder. She cocked her head back. What a weird keepsake! She laughed, Where would I keep it? Above the fireplace? How odd. She rolled her eyes, and started to cry again.
After another round of epinephrine, I started chest compressionsagain. Warm sweat seeped down my neck and back. In just 10 minutes, the 24‐bed pediatric intensive care unit (PICU) had become much smaller and more confined. Everyone funneled into this one room, this one bed. Beyond it was a blur of color and sound. I forced my strength onto Ricky, my 17‐year‐old patient with muscular dystrophy and end‐stage heart failure. He was admitted 1 week ago with respiratory distress, and he had only gotten worse since then.
Ricky's body, now cool and pale, was a blob of relaxed skin and loose bone beneath me. I straightened my arms, jutted the heel of my left hand over my right and pushed onto his chest. I pushed hard and fast, like I was taught; a dumb robotic motion again and again, trying to keep good position and form. I stared up at the monitor between every few compressions, looking at all the waveforms, anticipating, as if something on the screen was going to pop up suddenly and say EVERYTHING IS GOING TO BE OKAY. But it didn't.
I glanced beyond the bedside. There was a flurry of people bumping each other, asking for things, telling things, giving and receiving things. All of them were moving, but really had no place to go. This was the place. And in the far corner of the room, stood Mom and Dad.
In between the sink and recliner chair filled with clothes and books, they were the only people that stood still. Swollen feet planted in white socks. Their shoulders sagged.
I love you, I love you, Ricky. No, no, no. Mom and Dad kept on saying between sobs. I wondered if he could hear them. I wished he could hear them. Then I wished they would stop saying anything at all. I felt a rib give under my hands.
From the corner of my left eye, I saw Dad holding Mom upright by the wall. She wore red‐rimmed eyes and wet cheeks and took puttering breaths. Dad squeezed tissues in his hand, then into his eyes and nose and then back into his fist. They kept saying the words over and over, like they knew no other. I pushed harder and faster, but he didn't turn any pinker. Damn it. Damn it. There was plenty of noise, but above it all, I heard their voices. When I was told to hold compressions to check for a pulse, I stood still with my hands at my sides. I felt unnecessary. My precious little contribution to the commotion interrupted.
We all looked up at the monitor.
Stop, please stop. That's it, dad said, somewhere in the infinite pause. Mom still mumbled no over and over again. I turned to her and listened. I watched her pursed mouth and I imagined what it was Dad felt as he held her. Her body shook a Morse code into him, telling him it was time to give up. That it was over. That she couldn't take watching me pound away on her son's chest anymore. That it was okay to let Ricky rest. All the words that she couldn't find, or have the coordination to say, Dad translated for her.
He held her with a desperate grip, for a few moments longer. Maybe, the harder he squeezed, the more life he could push out of her, out of himself, and that effervescent pulse would find its way to their son's heart. But maybe all he could sense was her quiet internal whisper. And they told us again, as I remembered, just like all the soft conversations we had before in the back of the room, while Ricky slept, sedated on narcotics.
I put my fingers over his radial artery and closed my eyes.
Don't let Ricky feel pain, she said. It was the day we intubated him, only hours after he had been admitted.
Do what you can do, just don't Dad trailed off. He stared up at the ceiling and sighed. We listened to the gasp and hiss of the ventilator for a few more moments in silence.
We can try what you say, but no pain. We should know when to quitfor Ricky. Okay? Mom said, waiting for the tears as her nose moistened. She stared up at me.
Okay, I said. I nodded and stared back.
Dad squeezed her arm again, wrapped his around hers and massaged her. She had started to shake.
No pulse. I opened my eyes.
I stared at Ricky's face. His eyelids were half open, his lips were blue. No change on the monitor. I motioned to start compressions again.
Okay, Dad said.
Okay, stop! He's had enough. His dry lips and wet face moved and voiced the end. The room froze.
My muscles relaxed and I splayed my fingers wide, my way of showing that I was letting up. I watched myself lean back, unbelieving, and looked at the screen again. The rhythm drifted from pulseless electrical activity to asystole.
Mom and Dad simultaneously shut their eyes as if they saw something that we didn't and couldn't bear to see anymore. They opened them, looked at Ricky and slowly, as everyone stared, moved to the foot of the bed and began to rub his bare feet.
In subtle efficiency, the room was transformed. We turned off the monitors, we pushed out the carts and equipment, we picked up after ourselves, we dimmed the lights, we pulled the curtains and we left Mom and Dad with their son. Slow, deliberate whispers and motion now, it sounded empty without the background of rhythmic mechanical sounds. No dings, bleeps or rings; no pistons, suctions or pumps; only the occasional sound of tissue being ripped out of a box.
We sat with the family an hour later, in the conference room, to sign papers, for autopsy, for death certificates, for funeral preparations. Mom and Dad didn't know how to answer, and they drifted together to consider how they wanted Ricky's body cared for. Burial? Cremation?
I don't know, Mom said as she tried to fold the shredded tissues in her hand. He had a spinal rod placed his back years ago for his scoliosis. A titanium rod in his spine. Would that even burn? she asked.
We stared at each other, confused and unknowing.
We never thought of that, she said. She began to think out loud. If he were cremated, I don't think I'd want his spinal rod as a reminder. She cocked her head back. What a weird keepsake! She laughed, Where would I keep it? Above the fireplace? How odd. She rolled her eyes, and started to cry again.
Resource Utilization in Bacterial Meningitis
Bacterial meningitis can be a devastating disease in children. Overall mortality in children in the United States is 4%1 while long‐term morbidity is present in up to 25%2 of surviving children. The introduction of Haemophilus influenzae type B vaccine, heptavalent pneumococcal conjugate vaccine, and the quadrivalent meningococcal conjugate vaccine has altered the epidemiology of bacterial meningitis.24 Currently, little is known about the epidemiology of systemic complications and associated focal infections that occur during episodes of bacterial meningitis in children and how the presence of such complications affects in‐hospital healthcare resource utilization.
In a randomized controlled trial, the administration of adjuvant corticosteroids was associated with lower mortality rates in adults with bacterial meningitis due to all causes, with the greatest reduction in those with pneumococcal meningitis.5 In a post hoc analysis of data from this trial, reductions in systemic complications, such as septic shock, pneumonia, and acute respiratory distress syndrome, rather than neurologic complications were thought to be the underlying reason for the decrease in mortality associated with pneumococcal meningitis among corticosteroid recipients.6 However, children with bacterial meningitis have an overall 4‐fold lower mortality rate than adults with bacterial meningitis. An even greater difference in mortality rates exists between children and adults with pneumococcal meningitis.1, 5 Children do not benefit from adjuvant corticosteroids as adults do.1, 5, 7 Therefore, the pathogenesis of bacterial meningitis may differ in children from adults and account for the difference in response to adjuvant corticosteroids. Understanding the epidemiology of systemic complications and associated focal infections can aid in the understanding of the pathogenesis of the disease in varying age groups of children.
Previous studies in children have documented the frequency of certain bacterial meningitis‐associated conditions such as respiratory failure, pneumonia, endocarditis, and mastoiditis. Researchers have used the presence of such conditions to predict either mortality or neurologic sequelae in children.810 These studies were small and only included a few types of complications associated with bacterial meningitis. In‐hospital healthcare resource utilization, which may be an important indicator of in‐hospital morbidity, was also not considered as an outcome. In‐hospital morbidity may represent aspects of disease burden not captured by mortality rates or markers for long‐term morbidity alone. In future vaccine efficacy trails or novel therapeutics evaluations, consideration of these associated conditions is important.
The quantification of the use of in‐hospital healthcare utilization is also important for hospital planning and resource allocation in children with bacterial meningitis. A child presenting with bacterial meningitis and a systemic complication or an associated focal infection may require additional resource planning initially to expedite care to enhance recovery and decrease hospital length of stay (LOS).
Our goal was to document the frequency of bacterial meningitis‐associated conditions (systemic complications and associated focal infections) in a large cohort of children with bacterial meningitis treated at tertiary care children's hospitals in the United States, and determine how the presence of such conditions impacted in‐hospital healthcare resource utilization.
Patients and Methods
Data Source
Data for this retrospective cohort study was obtained from the Pediatric Health Information System (PHIS), a national administrative database containing data from 36 freestanding, tertiary care children's hospitals. These hospitals are affiliated with the Child Health Corporation of America (Shawnee Mission, KS), a business alliance of children's hospitals. Data quality and reliability are assured through a joint effort between the Child Health Corporation of America and participating hospitals. For the purposes of external benchmarking, participating hospitals provide discharge data including patient demographics, diagnoses, and procedures. Procedures to assure data validity were described previously.1 Total hospital charges are reported in the PHIS database and adjusted for hospital location using the Centers for Medicare and Medicaid price/wage index. A total of 27 participating hospitals also provide resource utilization data for each hospital discharge (ie, pharmaceutical dispensing, imaging, and laboratory studies); patients from these 27 hospitals were eligible for inclusion in this study. The protocol for the conduct of this study was reviewed and approved by The Children's Hospital of Philadelphia Committees for the Protection of Human Subjects.
Patients
Children less than 18 years of age with bacterial meningitis were eligible for this study if they were discharged from any of the 27 hospitals disclosing resource utilization data between January 1, 2001 and December 31, 2006. Study participants discharged with bacterial meningitis as their primary diagnosis were identified in the PHIS database using International Classification of Diseases, 9th revision, (ICD‐9) discharge diagnosis codes. The study population was limited to children without conditions predisposing to meningitis. Therefore, patients with ventricular shunts prior to the episode of bacterial meningitis were excluded using the following ICD‐9 procedure codes: ventricular shunt replacement (02.42); incision of peritoneum (54.95); removal of ventricular shunts (02.43); and the ICD‐9 discharge diagnosis code for mechanical complication of nervous system device, implant, and graft (996.2). Also, children with comorbid conditions that could predispose to meningitis or increase the likelihood of associated complications such as cancer (hematologic and nonhematologic), primary or secondary immunodeficiencies, prematurity, post‐operative infection, congenital cardiac disease, and sickle cell disease, were excluded from the analysis. Race and ethnicity were self‐reported by patients at time of admission.
Study Definitions
Study participants were identified from the PHIS database using ICD‐9 codes for the primary diagnosis of bacterial meningitis (codes 036.0‐036.1; 320.0‐320.3; 320.7; 320.81‐320.82; 320.89; 320.9). The sensitivity and specificity of ICD‐9 codes in identifying children with bacterial meningitis is unknown, however these codes have been used by previous investigators.1113 Bacterial meningitis associated‐conditions were classified as systemic complications (sepsis, systemic inflammatory response syndrome (SIRS), and respiratory failure) and associated focal infections (septic arthritis, mastoiditis, osteomyelitis, pneumonia and endocarditis). These associated conditions were identified by ICD‐9 discharge and procedural codes as listed in the Appendix (Supporting Information). Bone and joint infections were defined by the presence of either osteomyelitis or septic arthritis.
Primary Outcomes
The primary outcomes of interest were total in‐hospital charges and hospital LOS.
Measured Exposures
The primary exposures of interest were the occurrences of systemic complications, focal infections, or both conditions in children with bacterial meningitis.
Statistical Analysis
The data were initially described using frequencies and percentages for categorical variables and mean, median, interquartile ranges (IQRs) and range values for continuous variables. Analyses of bivariate associations between the outcomes (total in‐hospital charges and length of hospital stay) and potential covariates entailed either chi‐square tests or, for rare events with an expected frequency <5, Fishers Exact Test.
Following bivariate analysis, multivariable models were constructed to assess the adjusted impact of systemic complications and focal infection on total in‐hospital charges and hospital LOS. In evaluating total in‐hospital charges, the charge data were logarithmically transformed to account for the skewed distribution of charges. Multivariable linear regression was then performed to analyze the log transformed charges. The resulting beta‐coefficients were transformed to reflect the percent difference in total hospital charges between children with and without specific complications. In evaluating hospital LOS, negative binomial regression models were employed to estimate incidence rate ratios (IRRs) rather than log‐linear models, as to account for overdispersion in the outcome data. The negative binomial model produced a ratio of lengths of stay or IRR, where a ratio >1 indicates that the risk factor was associated with a longer LOS. The results were presented as percentage change to facilitate interpretation of the results.
The multivariable models were adjusted for the following confounders as determined a priori: age category, race, sex, vancomycin receipt, and adjuvant corticosteroid receipt within the first 24 hours of admission. Tests for interaction between systemic complications or focal infections and age were performed for each of these models. To address the possibility of referral bias which would lead us to overestimate the cost of caring for children with bacterial meningitis with an associated condition, the analyses were repeated restricting the sample to those children who had a lumber puncture performed at a PHIS‐participating hospital. The frequency of systemic complications and focal infections in those who were transferred was no different than in children who were not transferred; therefore the entire cohort was used in the final analyses. Sub‐group analyses were also performed for children identified with pneumococcal and meningococcal meningitis.
The standard errors for all estimates of covariate effects including metastatic effects under the above models were adjusted for the hospital to account for the increased variability due to clustering of individuals within hospitals. Two‐tailed P values <0.05 were considered statistically significant. Actual P values and 95% confidence intervals are reported. Data were analyzed using STATA, Version 10 (Stata Corporation, College Station, TX).
Results
Demographics
There were 2780 children admitted with bacterial meningitis during the study period; 461 (17%) children were excluded because of comorbid illness including malignancy (n = 37), congential heart disease (n = 231), prematurity (n = 104), human immunodeficiency virus infection (n = 4), sickle cell disease (n = 17), and post‐operative infection (n = 68). The remaining 2319 children with bacterial meningitis were included in the analyses. The mean age was 3.6 years (median, 1 year; IQR, 0‐6 years). Approximately half of the children were less than 1 year of age, 23% were 1 to 5 years, and 27% were >5 years. A total of 54% of children were white, 19% were black, 22% were Hispanic, and 5% were of other racial groups. Males accounted for 58% of the children. In this cohort of children, 9% received adjuvant corticosteroids within 24 hours of hospitalization.
Bacterial Meningitis‐Associated Conditions
Overall, 574 (25%) of children with bacterial meningitis suffered a systemic complication or an associated focal infection. Figure 1 shows the types of associated condition stratified by age category. Older children had a higher frequency of associated focal infections while younger children had a higher frequency of systemic complications (P = 0.002, chi‐square test for trend). Figure 2 shows the distribution of specific conditions among children in each age category. The frequency of sepsis decreased with age (P < 0.001, chi‐square test) while the frequency of mastoiditis (P < 0.001, Fisher's exact test) and osteomyelitis (P = 0.005, Fisher's exact test) increased with age. There did not appear to be substantial variability in the proportion of patients with SIRS or sepsis across hospitals, suggesting that hospital‐level variability in coding for these conditions was likely minimal. The median proportion of patients with SIRS by hospital was 2.4% (IQR, 1.2‐4.8%) while the median proportion of patients with sepsis by hospital was 13.4% (IQR, 10.0‐16.9%).
Of the 151 children with an associated focal infection, only 3 (2%) of children had more than 1 infection (1 child had mastoiditis and endocarditis, 1 child had pneumonia and osteomyelitis, and 1 child had pneumonia and endocarditis). However, of the 479 children with systemic complications, 116 (24%) had more than 1 systemic disease (Table 1).
| Types of Systemic Complications | Systemic Complications in All Bacterial Meningitis, n (%) | Systemic Complications in Meningococcal Meningitis, n (%) | Systemic Complications in Pneumococcal Meningitis, n (%) |
|---|---|---|---|
| |||
| Sepsis only | 209 (44) | 16 (21) | 69 (54) |
| Respiratory failure only | 139 (29) | 38 (49) | 30 (24) |
| SIRS only | 15 (3) | 9 (12) | 1 (1) |
| Sepsis and respiratory failure | 52 (11) | 4 (5) | 18 (14) |
| SIRS and sepsis | 27 (6) | 2 (3) | 4 (3) |
| SIRS and respiratory failure | 9 (2) | 5 (6) | 0 (0) |
| SIRS and respiratory failure and sepsis | 28 (6) | 3 (4) | 5 (4) |
| Total systemic complications | 479 | 77 | 127 |
In sub‐group analyses, 269 children had meningococcal meningitis and 470 children had pneumococcal meningitis. Of the children with meningococcal meningitis, 31.2% had a meningitis‐associated condition: 26.4% had a systemic complication, 2.6% had a focal infection, and 2.2% had both conditions. The most common associated conditions in children with meningococcal meningitis were respiratory failure (18.6%; n = 50), sepsis (9.3%; n = 25), and SIRS (7.1%; n = 19). In children with pneumococcal meningitis, 32.3% had a meningitis‐associated complication: 24.7% had a systemic complication, 5.3% had a focal infection, and 2.3% had both conditions. The most common associated conditions in children with pneumococcal meningitis were sepsis (20.4%; n = 96), respiratory failure (11.3%; n = 53), and pneumonia (4.7%; n = 22); mastoiditis was present in 2.3% (n = 11) of children with pneumococcal meningitis. Respiratory failure was more common in meningococcal meningitis (18.6%) than in pneumococcal meningitis (11.3%; P = 0.006). In contrast, sepsis was less common in meningococcal meningitis (9.3%) than in pneumococcal meningitis (20.4%; P < 0.001).
Hospital Charges
Overall, the median charges per hospital ranged from $20,158 to $53,823. In‐hospital charges for children with bacterial meningitis with and without any identified associated conditions are presented in Table 2. In multivariate analyses, the presence of systemic conditions, associated focal infections, or both conditions was independently associated with significantly higher total in‐hospital charges (Table 2). When conditions were considered individually, bone and joint infections (213% increase; 95% CI, 113‐260%), endocarditis (108% increase; 95% CI, 23‐258%), and pneumonia (107% increase; 95% CI, 58‐171%) were associated with the highest increases in total hospital charges (Figure 3). In contrast, SIRS and mastoiditis were not associated with higher hospital charges (Figure 3).
| Charges | LOS | |||
|---|---|---|---|---|
| Median, $ (IQR) | Adjusted Increase,* % (95% CI) | Median, days (IQR) | Adjusted Increase,* % (95% CI) | |
| ||||
| None (n = 1,745) | $27,110 (15,823‐48,307) | Reference** | 9 (6‐14) | Reference |
| Systemic (n = 423) | $66,690 (39,546136,756) | 136 (108269) | 14 (923) | 72 (5196) |
| Focal Infection (n = 95) | $58,016 (29,056125,813) | 118 (77168) | 13 (928) | 78 (40126) |
| Both (n = 56) | $130,744 (62,397299,288) | 351 (237503) | 21.5 (1245) | 211 (142303) |
LOS
The median LOS was 9 days (IQR, 6‐15 days); 5% of children had a LOS >42 days. Table 2 summarizes difference in LOS by the presence and absence of systemic conditions and focal infections. In multivariate analyses, the presence of systemic conditions, associated focal infections, or both conditions was independently associated with a significantly longer LOS (Table 2). When conditions were considered individually, endocarditis (152% increase; 95% CI, 60‐300%) and pneumonia (136% increase; 95% CI, 85‐201%) were associated with the greatest adjusted increases in LOS (Figure 4); only mastoiditis was not associated with an increased LOS compared with those without complications.
Discussion
To our knowledge, this is the first study to examine bacterial meningitis‐associated conditions in children and their impact on in‐hospital resource utilization. We found that 25% of the cohort of children with bacterial meningitis suffered from at least one focal infection or systemic complication. This represents a significant invasive disease burden among children with bacterial meningitis who do not have underlying comorbid conditions. Younger children were more likely to have systemic complications when compared with older children, specifically due to a higher frequency of sepsis in children <1 year. Older children were more likely to have an associated focal infection, specifically due to an increase in mastoiditis and osteomyelitis in children >1 year. Only 2% of children had more than 1 focal infection, while 24% of children had more than 1 systemic complication.
Importantly, the presence of a systemic complication in a child with bacterial meningitis increased their in‐hospital adjusted charges by 136%. The presence of a focal infection increased in‐hospital adjusted charges by 118%. A child with both a systemic complication and a focal infection and had a 351% increase in in‐hospital adjusted charges.
The presence of systemic complications or associated focal infections was significantly associated with higher in‐hospital charges and longer hospital LOS. Most individual meningitis‐associated conditions included in this study were associated with higher in‐hospital charges with the exception of SIRS and mastoiditis. All individual meningitis‐associated conditions were associated with a longer LOS except mastoiditis. This finding is not surprising as the LOS for children with mastoiditis is typically shorter than for children with bacterial meningitis. Glikich et al.14 reported a mean LOS of approximately 8 days for children with mastoiditis. As meningitis in the context of mastoiditis is likely caused by direct extension of infection, patients with meningitis and mastoiditis likely required extended hospitalization to treat meningitis rather than mastoiditis. In contrast, patients with meningitis occurring in the context of metastatic dissemination of infection (eg, endocarditis, pneumonia) often have hemodynamic instability requiring prolonged intensive care support.
A study of children with sepsis found that increasing severity of illness was associated with greater hospital resource utilization.15 Our study shows that this may also be true in children with bacterial meningitis. We found that in children with bacterial meningitis, having systemic complications or an associated focal infection was associated with greater in‐hospital resource utilization. This finding may therefore indicate greater in‐hospital morbidity among children with a bacterial meningitis‐associated condition. Since mortality rates for bacterial meningitis are low in children, in‐hospital morbidity may be a better indicator of disease burden.
Our data show that, in contrast to adults, bacterial meningitis in children is not typically associated with other focal infections. Some focal complications such as mastoiditis and osteomyelitis disproportionately affect older children. These complications are typically accompanied by overt clinical manifestations. Therefore, we believe that the evaluation for the presence of concomitant focal infections can be guided by clinical examination findings and that routine radiologic evaluation for focal complications may not be necessary. Additionally, focal infections tend to occur in the absence of concomitant systemic complications. Of the 151 children with at least 1 associated focal infection, only 37% had a systemic complication. Bacterial meningitis may lie on a continuum of invasive disease depending on the virulence factors of the invading pathogen as well as specific host factors. Understanding the epidemiology of these associated conditions can enhance our understanding of the pathogenesis of bacterial meningitis in children. Understanding why some children suffer from septicemia rather than bacteremia may help in developing novel therapeutics.
There are several limitations to our study. First, since we identified focal infections and systemic complications using billing charges and ICD‐9 discharge diagnosis codes, it was impossible to determine when these conditions represented true complications of bacterial meningitis and when they represented the primary source of infection. Therefore, some of our primary outcomes may represent the cause of meningitis rather than a direct complication. We attempted to minimize such misclassification by limiting the cohort to those with a primary discharge diagnosis of bacterial meningitis though such misclassification is still possible.
Second, the use of ICD‐9 codes to accurately identify systemic complications and associated focal infections is a potential limitation. For example, respiratory failure, defined as the requirement of endotracheal intubation in our study, may not capture children receiving non‐invasive mechanical ventilation (eg, bilevel positive airway pressure). If use of noninvasive ventilation strategies did not depend exclusively on illness severity, our study would underestimate the frequency of respiratory failure. Furthermore, there may be inconsistencies among pediatric physicians in coding conditions such as SIRS and sepsis. Even in the clinical setting, a uniform definition of SIRS and sepsis is problematic due to physiologic differences between adults and children of varying age groups.16 An international panel of pediatricians proposed age‐specific definitions for sepsis and SIRS, while acknowledging the paucity of evidence to support some of their recommendations.16 None of the proposed definitions could be applied using administrative data. Limitations in the use of ICD‐9 discharge diagnosis codes to identify children with bacterial meningitis were discussed previously.1
Third, only free‐standing children's hospitals were included in the analysis. It is likely that many children with uncomplicated bacterial meningitis are treated at community hospitals or smaller academic centers. Our study may overestimate the rate of bacterial meningitis‐associated focal infections and systemic complications since participating hospitals serve as regional referral centers. To address the potential for such referral bias, we repeated the analysis while restricting the cohort to those children who had a lumbar puncture performed at the treating facility. No difference in frequency of associated conditions or in‐hospital resource utilization was found between children transferred and children not transferred. Finally, the PHIS database reports billed charge data rather than cost data. Billed data may overestimate the actual economic impact of bacterial meningitis‐associated complications since payers often reimburse at lesser rates. Resource utilization may also vary widely between hospitals and geographic locations as previously shown.15
In conclusion, bacterial meningitis remains an important cause of morbidity in children. Systemic complications such as sepsis and respiratory failure are common. Respiratory failure occurred more commonly among patients with meningococcal meningitis while sepsis occurred more commonly among patients with pneumococcal meningitis. While focal complications are uncommon, children >5 years of age are more likely than younger children to have concomitant mastoiditis or osteomyelitis. The presence of both systemic and focal complications is associated with substantially greater resource utilization than either complication alone.
Dr. Shah had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the analysis. Study concept and design: Shah, Mongelluzzo; acquisition of data: Shah, Mohamad; analysis and interpretation of data: Mongelluzzo, Mohamad, Ten Have, Shah; drafting of the manuscript: Mongelluzzo; critical revision of the manuscript for important intellectual content: Mongelluzzo, Mohamad, Ten Have, Shah; statistical analysis: Shah, Mongelluzzo, Ten Have; obtained funding: Shah, Mongelluzzo; administrative, technical, or material support: Shah; study supervision: Shah.
Appendix
Diagnosis Codes:
Endocarditis: 421.0, 421.1, 421.9
Mastoiditis: 383.0, 383.1, 383.2, 383.8, 383.9
Osteomyelitis: 730.0, 730.1, 730.2, 730.3, 730.7, 730.8, 730.9
Septic arthritis: 711.0, 711.1, 711.2, 711.3, 711.4, 711.5, 711.6, 711.7, 711.8, 711.9
Sepsis: 038.0, 038.1, 038.2, 038.3, 038.4, 038.8, 038.9
Systemic Inflammatory Response Syndrome: 995.92
Pneumonia: 480.0, 480.1, 480.2, 480.3, 480.8, 480.9, 481, 482.0, 482.1, 482.2, 482.3, 482.4, 482.8, 482.9, 483.0, 483.1, 483.8, 484.1, 484.3, 484.5, 484.6, 484.7, 484.8, 485, 486
Procedure Codes:
Endotracheal Intubation: 96.04
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- , .Dexamethasone and pneumococcal meningitis.Ann Intern Med.2004;141:327.
- , , , et al.Dexamethasone in Vietnamese adolescents and adults with bacterial meningitis.N Engl J Med.2007;357:2431–2440.
- , , , , .Bacterial meningitis in an urban area: etiologic study and prognostic factors.Infection.2007;35:406–413.
- , , .Clinical features and prognostic factors in childhood pneumococcal meningitis.J Microbiol Immunol Infect.2008;41:48–53.
- , , .Clinical presentation and prognostic factors of Streptococcus pneumoniae meningitis according to the focus of infection.BMC Infect Dis.2005;5:93.
- , .Trends in invasive pneumococcal disease‐associated hospitalizations.Clin Infect Dis.2006;42:e1–e5.
- , , .Managing meningococcal disease in the United States: Hospital case characteristics and costs by age.Value Health.2006;9:236–243.
- , , , , , .Population‐based analysis of meningococcal disease mortality in the United States: 1990–2002.Pediatr Infect Dis J.2006;25:191–194.
- , , , .A contemporary analysis of acute mastoiditis.Arch Otolaryngol Head Neck Surg.1996;122:135–139.
- , , .Patient and hospital correlates of clinical outcomes and resource utilization in severe pediatric sepsis.Pediatrics.2007;119:487–494.
- , , .International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics.Pediatr Crit Care Med.2005;6:2–8.
Bacterial meningitis can be a devastating disease in children. Overall mortality in children in the United States is 4%1 while long‐term morbidity is present in up to 25%2 of surviving children. The introduction of Haemophilus influenzae type B vaccine, heptavalent pneumococcal conjugate vaccine, and the quadrivalent meningococcal conjugate vaccine has altered the epidemiology of bacterial meningitis.24 Currently, little is known about the epidemiology of systemic complications and associated focal infections that occur during episodes of bacterial meningitis in children and how the presence of such complications affects in‐hospital healthcare resource utilization.
In a randomized controlled trial, the administration of adjuvant corticosteroids was associated with lower mortality rates in adults with bacterial meningitis due to all causes, with the greatest reduction in those with pneumococcal meningitis.5 In a post hoc analysis of data from this trial, reductions in systemic complications, such as septic shock, pneumonia, and acute respiratory distress syndrome, rather than neurologic complications were thought to be the underlying reason for the decrease in mortality associated with pneumococcal meningitis among corticosteroid recipients.6 However, children with bacterial meningitis have an overall 4‐fold lower mortality rate than adults with bacterial meningitis. An even greater difference in mortality rates exists between children and adults with pneumococcal meningitis.1, 5 Children do not benefit from adjuvant corticosteroids as adults do.1, 5, 7 Therefore, the pathogenesis of bacterial meningitis may differ in children from adults and account for the difference in response to adjuvant corticosteroids. Understanding the epidemiology of systemic complications and associated focal infections can aid in the understanding of the pathogenesis of the disease in varying age groups of children.
Previous studies in children have documented the frequency of certain bacterial meningitis‐associated conditions such as respiratory failure, pneumonia, endocarditis, and mastoiditis. Researchers have used the presence of such conditions to predict either mortality or neurologic sequelae in children.810 These studies were small and only included a few types of complications associated with bacterial meningitis. In‐hospital healthcare resource utilization, which may be an important indicator of in‐hospital morbidity, was also not considered as an outcome. In‐hospital morbidity may represent aspects of disease burden not captured by mortality rates or markers for long‐term morbidity alone. In future vaccine efficacy trails or novel therapeutics evaluations, consideration of these associated conditions is important.
The quantification of the use of in‐hospital healthcare utilization is also important for hospital planning and resource allocation in children with bacterial meningitis. A child presenting with bacterial meningitis and a systemic complication or an associated focal infection may require additional resource planning initially to expedite care to enhance recovery and decrease hospital length of stay (LOS).
Our goal was to document the frequency of bacterial meningitis‐associated conditions (systemic complications and associated focal infections) in a large cohort of children with bacterial meningitis treated at tertiary care children's hospitals in the United States, and determine how the presence of such conditions impacted in‐hospital healthcare resource utilization.
Patients and Methods
Data Source
Data for this retrospective cohort study was obtained from the Pediatric Health Information System (PHIS), a national administrative database containing data from 36 freestanding, tertiary care children's hospitals. These hospitals are affiliated with the Child Health Corporation of America (Shawnee Mission, KS), a business alliance of children's hospitals. Data quality and reliability are assured through a joint effort between the Child Health Corporation of America and participating hospitals. For the purposes of external benchmarking, participating hospitals provide discharge data including patient demographics, diagnoses, and procedures. Procedures to assure data validity were described previously.1 Total hospital charges are reported in the PHIS database and adjusted for hospital location using the Centers for Medicare and Medicaid price/wage index. A total of 27 participating hospitals also provide resource utilization data for each hospital discharge (ie, pharmaceutical dispensing, imaging, and laboratory studies); patients from these 27 hospitals were eligible for inclusion in this study. The protocol for the conduct of this study was reviewed and approved by The Children's Hospital of Philadelphia Committees for the Protection of Human Subjects.
Patients
Children less than 18 years of age with bacterial meningitis were eligible for this study if they were discharged from any of the 27 hospitals disclosing resource utilization data between January 1, 2001 and December 31, 2006. Study participants discharged with bacterial meningitis as their primary diagnosis were identified in the PHIS database using International Classification of Diseases, 9th revision, (ICD‐9) discharge diagnosis codes. The study population was limited to children without conditions predisposing to meningitis. Therefore, patients with ventricular shunts prior to the episode of bacterial meningitis were excluded using the following ICD‐9 procedure codes: ventricular shunt replacement (02.42); incision of peritoneum (54.95); removal of ventricular shunts (02.43); and the ICD‐9 discharge diagnosis code for mechanical complication of nervous system device, implant, and graft (996.2). Also, children with comorbid conditions that could predispose to meningitis or increase the likelihood of associated complications such as cancer (hematologic and nonhematologic), primary or secondary immunodeficiencies, prematurity, post‐operative infection, congenital cardiac disease, and sickle cell disease, were excluded from the analysis. Race and ethnicity were self‐reported by patients at time of admission.
Study Definitions
Study participants were identified from the PHIS database using ICD‐9 codes for the primary diagnosis of bacterial meningitis (codes 036.0‐036.1; 320.0‐320.3; 320.7; 320.81‐320.82; 320.89; 320.9). The sensitivity and specificity of ICD‐9 codes in identifying children with bacterial meningitis is unknown, however these codes have been used by previous investigators.1113 Bacterial meningitis associated‐conditions were classified as systemic complications (sepsis, systemic inflammatory response syndrome (SIRS), and respiratory failure) and associated focal infections (septic arthritis, mastoiditis, osteomyelitis, pneumonia and endocarditis). These associated conditions were identified by ICD‐9 discharge and procedural codes as listed in the Appendix (Supporting Information). Bone and joint infections were defined by the presence of either osteomyelitis or septic arthritis.
Primary Outcomes
The primary outcomes of interest were total in‐hospital charges and hospital LOS.
Measured Exposures
The primary exposures of interest were the occurrences of systemic complications, focal infections, or both conditions in children with bacterial meningitis.
Statistical Analysis
The data were initially described using frequencies and percentages for categorical variables and mean, median, interquartile ranges (IQRs) and range values for continuous variables. Analyses of bivariate associations between the outcomes (total in‐hospital charges and length of hospital stay) and potential covariates entailed either chi‐square tests or, for rare events with an expected frequency <5, Fishers Exact Test.
Following bivariate analysis, multivariable models were constructed to assess the adjusted impact of systemic complications and focal infection on total in‐hospital charges and hospital LOS. In evaluating total in‐hospital charges, the charge data were logarithmically transformed to account for the skewed distribution of charges. Multivariable linear regression was then performed to analyze the log transformed charges. The resulting beta‐coefficients were transformed to reflect the percent difference in total hospital charges between children with and without specific complications. In evaluating hospital LOS, negative binomial regression models were employed to estimate incidence rate ratios (IRRs) rather than log‐linear models, as to account for overdispersion in the outcome data. The negative binomial model produced a ratio of lengths of stay or IRR, where a ratio >1 indicates that the risk factor was associated with a longer LOS. The results were presented as percentage change to facilitate interpretation of the results.
The multivariable models were adjusted for the following confounders as determined a priori: age category, race, sex, vancomycin receipt, and adjuvant corticosteroid receipt within the first 24 hours of admission. Tests for interaction between systemic complications or focal infections and age were performed for each of these models. To address the possibility of referral bias which would lead us to overestimate the cost of caring for children with bacterial meningitis with an associated condition, the analyses were repeated restricting the sample to those children who had a lumber puncture performed at a PHIS‐participating hospital. The frequency of systemic complications and focal infections in those who were transferred was no different than in children who were not transferred; therefore the entire cohort was used in the final analyses. Sub‐group analyses were also performed for children identified with pneumococcal and meningococcal meningitis.
The standard errors for all estimates of covariate effects including metastatic effects under the above models were adjusted for the hospital to account for the increased variability due to clustering of individuals within hospitals. Two‐tailed P values <0.05 were considered statistically significant. Actual P values and 95% confidence intervals are reported. Data were analyzed using STATA, Version 10 (Stata Corporation, College Station, TX).
Results
Demographics
There were 2780 children admitted with bacterial meningitis during the study period; 461 (17%) children were excluded because of comorbid illness including malignancy (n = 37), congential heart disease (n = 231), prematurity (n = 104), human immunodeficiency virus infection (n = 4), sickle cell disease (n = 17), and post‐operative infection (n = 68). The remaining 2319 children with bacterial meningitis were included in the analyses. The mean age was 3.6 years (median, 1 year; IQR, 0‐6 years). Approximately half of the children were less than 1 year of age, 23% were 1 to 5 years, and 27% were >5 years. A total of 54% of children were white, 19% were black, 22% were Hispanic, and 5% were of other racial groups. Males accounted for 58% of the children. In this cohort of children, 9% received adjuvant corticosteroids within 24 hours of hospitalization.
Bacterial Meningitis‐Associated Conditions
Overall, 574 (25%) of children with bacterial meningitis suffered a systemic complication or an associated focal infection. Figure 1 shows the types of associated condition stratified by age category. Older children had a higher frequency of associated focal infections while younger children had a higher frequency of systemic complications (P = 0.002, chi‐square test for trend). Figure 2 shows the distribution of specific conditions among children in each age category. The frequency of sepsis decreased with age (P < 0.001, chi‐square test) while the frequency of mastoiditis (P < 0.001, Fisher's exact test) and osteomyelitis (P = 0.005, Fisher's exact test) increased with age. There did not appear to be substantial variability in the proportion of patients with SIRS or sepsis across hospitals, suggesting that hospital‐level variability in coding for these conditions was likely minimal. The median proportion of patients with SIRS by hospital was 2.4% (IQR, 1.2‐4.8%) while the median proportion of patients with sepsis by hospital was 13.4% (IQR, 10.0‐16.9%).
Of the 151 children with an associated focal infection, only 3 (2%) of children had more than 1 infection (1 child had mastoiditis and endocarditis, 1 child had pneumonia and osteomyelitis, and 1 child had pneumonia and endocarditis). However, of the 479 children with systemic complications, 116 (24%) had more than 1 systemic disease (Table 1).
| Types of Systemic Complications | Systemic Complications in All Bacterial Meningitis, n (%) | Systemic Complications in Meningococcal Meningitis, n (%) | Systemic Complications in Pneumococcal Meningitis, n (%) |
|---|---|---|---|
| |||
| Sepsis only | 209 (44) | 16 (21) | 69 (54) |
| Respiratory failure only | 139 (29) | 38 (49) | 30 (24) |
| SIRS only | 15 (3) | 9 (12) | 1 (1) |
| Sepsis and respiratory failure | 52 (11) | 4 (5) | 18 (14) |
| SIRS and sepsis | 27 (6) | 2 (3) | 4 (3) |
| SIRS and respiratory failure | 9 (2) | 5 (6) | 0 (0) |
| SIRS and respiratory failure and sepsis | 28 (6) | 3 (4) | 5 (4) |
| Total systemic complications | 479 | 77 | 127 |
In sub‐group analyses, 269 children had meningococcal meningitis and 470 children had pneumococcal meningitis. Of the children with meningococcal meningitis, 31.2% had a meningitis‐associated condition: 26.4% had a systemic complication, 2.6% had a focal infection, and 2.2% had both conditions. The most common associated conditions in children with meningococcal meningitis were respiratory failure (18.6%; n = 50), sepsis (9.3%; n = 25), and SIRS (7.1%; n = 19). In children with pneumococcal meningitis, 32.3% had a meningitis‐associated complication: 24.7% had a systemic complication, 5.3% had a focal infection, and 2.3% had both conditions. The most common associated conditions in children with pneumococcal meningitis were sepsis (20.4%; n = 96), respiratory failure (11.3%; n = 53), and pneumonia (4.7%; n = 22); mastoiditis was present in 2.3% (n = 11) of children with pneumococcal meningitis. Respiratory failure was more common in meningococcal meningitis (18.6%) than in pneumococcal meningitis (11.3%; P = 0.006). In contrast, sepsis was less common in meningococcal meningitis (9.3%) than in pneumococcal meningitis (20.4%; P < 0.001).
Hospital Charges
Overall, the median charges per hospital ranged from $20,158 to $53,823. In‐hospital charges for children with bacterial meningitis with and without any identified associated conditions are presented in Table 2. In multivariate analyses, the presence of systemic conditions, associated focal infections, or both conditions was independently associated with significantly higher total in‐hospital charges (Table 2). When conditions were considered individually, bone and joint infections (213% increase; 95% CI, 113‐260%), endocarditis (108% increase; 95% CI, 23‐258%), and pneumonia (107% increase; 95% CI, 58‐171%) were associated with the highest increases in total hospital charges (Figure 3). In contrast, SIRS and mastoiditis were not associated with higher hospital charges (Figure 3).
| Charges | LOS | |||
|---|---|---|---|---|
| Median, $ (IQR) | Adjusted Increase,* % (95% CI) | Median, days (IQR) | Adjusted Increase,* % (95% CI) | |
| ||||
| None (n = 1,745) | $27,110 (15,823‐48,307) | Reference** | 9 (6‐14) | Reference |
| Systemic (n = 423) | $66,690 (39,546136,756) | 136 (108269) | 14 (923) | 72 (5196) |
| Focal Infection (n = 95) | $58,016 (29,056125,813) | 118 (77168) | 13 (928) | 78 (40126) |
| Both (n = 56) | $130,744 (62,397299,288) | 351 (237503) | 21.5 (1245) | 211 (142303) |
LOS
The median LOS was 9 days (IQR, 6‐15 days); 5% of children had a LOS >42 days. Table 2 summarizes difference in LOS by the presence and absence of systemic conditions and focal infections. In multivariate analyses, the presence of systemic conditions, associated focal infections, or both conditions was independently associated with a significantly longer LOS (Table 2). When conditions were considered individually, endocarditis (152% increase; 95% CI, 60‐300%) and pneumonia (136% increase; 95% CI, 85‐201%) were associated with the greatest adjusted increases in LOS (Figure 4); only mastoiditis was not associated with an increased LOS compared with those without complications.
Discussion
To our knowledge, this is the first study to examine bacterial meningitis‐associated conditions in children and their impact on in‐hospital resource utilization. We found that 25% of the cohort of children with bacterial meningitis suffered from at least one focal infection or systemic complication. This represents a significant invasive disease burden among children with bacterial meningitis who do not have underlying comorbid conditions. Younger children were more likely to have systemic complications when compared with older children, specifically due to a higher frequency of sepsis in children <1 year. Older children were more likely to have an associated focal infection, specifically due to an increase in mastoiditis and osteomyelitis in children >1 year. Only 2% of children had more than 1 focal infection, while 24% of children had more than 1 systemic complication.
Importantly, the presence of a systemic complication in a child with bacterial meningitis increased their in‐hospital adjusted charges by 136%. The presence of a focal infection increased in‐hospital adjusted charges by 118%. A child with both a systemic complication and a focal infection and had a 351% increase in in‐hospital adjusted charges.
The presence of systemic complications or associated focal infections was significantly associated with higher in‐hospital charges and longer hospital LOS. Most individual meningitis‐associated conditions included in this study were associated with higher in‐hospital charges with the exception of SIRS and mastoiditis. All individual meningitis‐associated conditions were associated with a longer LOS except mastoiditis. This finding is not surprising as the LOS for children with mastoiditis is typically shorter than for children with bacterial meningitis. Glikich et al.14 reported a mean LOS of approximately 8 days for children with mastoiditis. As meningitis in the context of mastoiditis is likely caused by direct extension of infection, patients with meningitis and mastoiditis likely required extended hospitalization to treat meningitis rather than mastoiditis. In contrast, patients with meningitis occurring in the context of metastatic dissemination of infection (eg, endocarditis, pneumonia) often have hemodynamic instability requiring prolonged intensive care support.
A study of children with sepsis found that increasing severity of illness was associated with greater hospital resource utilization.15 Our study shows that this may also be true in children with bacterial meningitis. We found that in children with bacterial meningitis, having systemic complications or an associated focal infection was associated with greater in‐hospital resource utilization. This finding may therefore indicate greater in‐hospital morbidity among children with a bacterial meningitis‐associated condition. Since mortality rates for bacterial meningitis are low in children, in‐hospital morbidity may be a better indicator of disease burden.
Our data show that, in contrast to adults, bacterial meningitis in children is not typically associated with other focal infections. Some focal complications such as mastoiditis and osteomyelitis disproportionately affect older children. These complications are typically accompanied by overt clinical manifestations. Therefore, we believe that the evaluation for the presence of concomitant focal infections can be guided by clinical examination findings and that routine radiologic evaluation for focal complications may not be necessary. Additionally, focal infections tend to occur in the absence of concomitant systemic complications. Of the 151 children with at least 1 associated focal infection, only 37% had a systemic complication. Bacterial meningitis may lie on a continuum of invasive disease depending on the virulence factors of the invading pathogen as well as specific host factors. Understanding the epidemiology of these associated conditions can enhance our understanding of the pathogenesis of bacterial meningitis in children. Understanding why some children suffer from septicemia rather than bacteremia may help in developing novel therapeutics.
There are several limitations to our study. First, since we identified focal infections and systemic complications using billing charges and ICD‐9 discharge diagnosis codes, it was impossible to determine when these conditions represented true complications of bacterial meningitis and when they represented the primary source of infection. Therefore, some of our primary outcomes may represent the cause of meningitis rather than a direct complication. We attempted to minimize such misclassification by limiting the cohort to those with a primary discharge diagnosis of bacterial meningitis though such misclassification is still possible.
Second, the use of ICD‐9 codes to accurately identify systemic complications and associated focal infections is a potential limitation. For example, respiratory failure, defined as the requirement of endotracheal intubation in our study, may not capture children receiving non‐invasive mechanical ventilation (eg, bilevel positive airway pressure). If use of noninvasive ventilation strategies did not depend exclusively on illness severity, our study would underestimate the frequency of respiratory failure. Furthermore, there may be inconsistencies among pediatric physicians in coding conditions such as SIRS and sepsis. Even in the clinical setting, a uniform definition of SIRS and sepsis is problematic due to physiologic differences between adults and children of varying age groups.16 An international panel of pediatricians proposed age‐specific definitions for sepsis and SIRS, while acknowledging the paucity of evidence to support some of their recommendations.16 None of the proposed definitions could be applied using administrative data. Limitations in the use of ICD‐9 discharge diagnosis codes to identify children with bacterial meningitis were discussed previously.1
Third, only free‐standing children's hospitals were included in the analysis. It is likely that many children with uncomplicated bacterial meningitis are treated at community hospitals or smaller academic centers. Our study may overestimate the rate of bacterial meningitis‐associated focal infections and systemic complications since participating hospitals serve as regional referral centers. To address the potential for such referral bias, we repeated the analysis while restricting the cohort to those children who had a lumbar puncture performed at the treating facility. No difference in frequency of associated conditions or in‐hospital resource utilization was found between children transferred and children not transferred. Finally, the PHIS database reports billed charge data rather than cost data. Billed data may overestimate the actual economic impact of bacterial meningitis‐associated complications since payers often reimburse at lesser rates. Resource utilization may also vary widely between hospitals and geographic locations as previously shown.15
In conclusion, bacterial meningitis remains an important cause of morbidity in children. Systemic complications such as sepsis and respiratory failure are common. Respiratory failure occurred more commonly among patients with meningococcal meningitis while sepsis occurred more commonly among patients with pneumococcal meningitis. While focal complications are uncommon, children >5 years of age are more likely than younger children to have concomitant mastoiditis or osteomyelitis. The presence of both systemic and focal complications is associated with substantially greater resource utilization than either complication alone.
Dr. Shah had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the analysis. Study concept and design: Shah, Mongelluzzo; acquisition of data: Shah, Mohamad; analysis and interpretation of data: Mongelluzzo, Mohamad, Ten Have, Shah; drafting of the manuscript: Mongelluzzo; critical revision of the manuscript for important intellectual content: Mongelluzzo, Mohamad, Ten Have, Shah; statistical analysis: Shah, Mongelluzzo, Ten Have; obtained funding: Shah, Mongelluzzo; administrative, technical, or material support: Shah; study supervision: Shah.
Appendix
Diagnosis Codes:
Endocarditis: 421.0, 421.1, 421.9
Mastoiditis: 383.0, 383.1, 383.2, 383.8, 383.9
Osteomyelitis: 730.0, 730.1, 730.2, 730.3, 730.7, 730.8, 730.9
Septic arthritis: 711.0, 711.1, 711.2, 711.3, 711.4, 711.5, 711.6, 711.7, 711.8, 711.9
Sepsis: 038.0, 038.1, 038.2, 038.3, 038.4, 038.8, 038.9
Systemic Inflammatory Response Syndrome: 995.92
Pneumonia: 480.0, 480.1, 480.2, 480.3, 480.8, 480.9, 481, 482.0, 482.1, 482.2, 482.3, 482.4, 482.8, 482.9, 483.0, 483.1, 483.8, 484.1, 484.3, 484.5, 484.6, 484.7, 484.8, 485, 486
Procedure Codes:
Endotracheal Intubation: 96.04
Bacterial meningitis can be a devastating disease in children. Overall mortality in children in the United States is 4%1 while long‐term morbidity is present in up to 25%2 of surviving children. The introduction of Haemophilus influenzae type B vaccine, heptavalent pneumococcal conjugate vaccine, and the quadrivalent meningococcal conjugate vaccine has altered the epidemiology of bacterial meningitis.24 Currently, little is known about the epidemiology of systemic complications and associated focal infections that occur during episodes of bacterial meningitis in children and how the presence of such complications affects in‐hospital healthcare resource utilization.
In a randomized controlled trial, the administration of adjuvant corticosteroids was associated with lower mortality rates in adults with bacterial meningitis due to all causes, with the greatest reduction in those with pneumococcal meningitis.5 In a post hoc analysis of data from this trial, reductions in systemic complications, such as septic shock, pneumonia, and acute respiratory distress syndrome, rather than neurologic complications were thought to be the underlying reason for the decrease in mortality associated with pneumococcal meningitis among corticosteroid recipients.6 However, children with bacterial meningitis have an overall 4‐fold lower mortality rate than adults with bacterial meningitis. An even greater difference in mortality rates exists between children and adults with pneumococcal meningitis.1, 5 Children do not benefit from adjuvant corticosteroids as adults do.1, 5, 7 Therefore, the pathogenesis of bacterial meningitis may differ in children from adults and account for the difference in response to adjuvant corticosteroids. Understanding the epidemiology of systemic complications and associated focal infections can aid in the understanding of the pathogenesis of the disease in varying age groups of children.
Previous studies in children have documented the frequency of certain bacterial meningitis‐associated conditions such as respiratory failure, pneumonia, endocarditis, and mastoiditis. Researchers have used the presence of such conditions to predict either mortality or neurologic sequelae in children.810 These studies were small and only included a few types of complications associated with bacterial meningitis. In‐hospital healthcare resource utilization, which may be an important indicator of in‐hospital morbidity, was also not considered as an outcome. In‐hospital morbidity may represent aspects of disease burden not captured by mortality rates or markers for long‐term morbidity alone. In future vaccine efficacy trails or novel therapeutics evaluations, consideration of these associated conditions is important.
The quantification of the use of in‐hospital healthcare utilization is also important for hospital planning and resource allocation in children with bacterial meningitis. A child presenting with bacterial meningitis and a systemic complication or an associated focal infection may require additional resource planning initially to expedite care to enhance recovery and decrease hospital length of stay (LOS).
Our goal was to document the frequency of bacterial meningitis‐associated conditions (systemic complications and associated focal infections) in a large cohort of children with bacterial meningitis treated at tertiary care children's hospitals in the United States, and determine how the presence of such conditions impacted in‐hospital healthcare resource utilization.
Patients and Methods
Data Source
Data for this retrospective cohort study was obtained from the Pediatric Health Information System (PHIS), a national administrative database containing data from 36 freestanding, tertiary care children's hospitals. These hospitals are affiliated with the Child Health Corporation of America (Shawnee Mission, KS), a business alliance of children's hospitals. Data quality and reliability are assured through a joint effort between the Child Health Corporation of America and participating hospitals. For the purposes of external benchmarking, participating hospitals provide discharge data including patient demographics, diagnoses, and procedures. Procedures to assure data validity were described previously.1 Total hospital charges are reported in the PHIS database and adjusted for hospital location using the Centers for Medicare and Medicaid price/wage index. A total of 27 participating hospitals also provide resource utilization data for each hospital discharge (ie, pharmaceutical dispensing, imaging, and laboratory studies); patients from these 27 hospitals were eligible for inclusion in this study. The protocol for the conduct of this study was reviewed and approved by The Children's Hospital of Philadelphia Committees for the Protection of Human Subjects.
Patients
Children less than 18 years of age with bacterial meningitis were eligible for this study if they were discharged from any of the 27 hospitals disclosing resource utilization data between January 1, 2001 and December 31, 2006. Study participants discharged with bacterial meningitis as their primary diagnosis were identified in the PHIS database using International Classification of Diseases, 9th revision, (ICD‐9) discharge diagnosis codes. The study population was limited to children without conditions predisposing to meningitis. Therefore, patients with ventricular shunts prior to the episode of bacterial meningitis were excluded using the following ICD‐9 procedure codes: ventricular shunt replacement (02.42); incision of peritoneum (54.95); removal of ventricular shunts (02.43); and the ICD‐9 discharge diagnosis code for mechanical complication of nervous system device, implant, and graft (996.2). Also, children with comorbid conditions that could predispose to meningitis or increase the likelihood of associated complications such as cancer (hematologic and nonhematologic), primary or secondary immunodeficiencies, prematurity, post‐operative infection, congenital cardiac disease, and sickle cell disease, were excluded from the analysis. Race and ethnicity were self‐reported by patients at time of admission.
Study Definitions
Study participants were identified from the PHIS database using ICD‐9 codes for the primary diagnosis of bacterial meningitis (codes 036.0‐036.1; 320.0‐320.3; 320.7; 320.81‐320.82; 320.89; 320.9). The sensitivity and specificity of ICD‐9 codes in identifying children with bacterial meningitis is unknown, however these codes have been used by previous investigators.1113 Bacterial meningitis associated‐conditions were classified as systemic complications (sepsis, systemic inflammatory response syndrome (SIRS), and respiratory failure) and associated focal infections (septic arthritis, mastoiditis, osteomyelitis, pneumonia and endocarditis). These associated conditions were identified by ICD‐9 discharge and procedural codes as listed in the Appendix (Supporting Information). Bone and joint infections were defined by the presence of either osteomyelitis or septic arthritis.
Primary Outcomes
The primary outcomes of interest were total in‐hospital charges and hospital LOS.
Measured Exposures
The primary exposures of interest were the occurrences of systemic complications, focal infections, or both conditions in children with bacterial meningitis.
Statistical Analysis
The data were initially described using frequencies and percentages for categorical variables and mean, median, interquartile ranges (IQRs) and range values for continuous variables. Analyses of bivariate associations between the outcomes (total in‐hospital charges and length of hospital stay) and potential covariates entailed either chi‐square tests or, for rare events with an expected frequency <5, Fishers Exact Test.
Following bivariate analysis, multivariable models were constructed to assess the adjusted impact of systemic complications and focal infection on total in‐hospital charges and hospital LOS. In evaluating total in‐hospital charges, the charge data were logarithmically transformed to account for the skewed distribution of charges. Multivariable linear regression was then performed to analyze the log transformed charges. The resulting beta‐coefficients were transformed to reflect the percent difference in total hospital charges between children with and without specific complications. In evaluating hospital LOS, negative binomial regression models were employed to estimate incidence rate ratios (IRRs) rather than log‐linear models, as to account for overdispersion in the outcome data. The negative binomial model produced a ratio of lengths of stay or IRR, where a ratio >1 indicates that the risk factor was associated with a longer LOS. The results were presented as percentage change to facilitate interpretation of the results.
The multivariable models were adjusted for the following confounders as determined a priori: age category, race, sex, vancomycin receipt, and adjuvant corticosteroid receipt within the first 24 hours of admission. Tests for interaction between systemic complications or focal infections and age were performed for each of these models. To address the possibility of referral bias which would lead us to overestimate the cost of caring for children with bacterial meningitis with an associated condition, the analyses were repeated restricting the sample to those children who had a lumber puncture performed at a PHIS‐participating hospital. The frequency of systemic complications and focal infections in those who were transferred was no different than in children who were not transferred; therefore the entire cohort was used in the final analyses. Sub‐group analyses were also performed for children identified with pneumococcal and meningococcal meningitis.
The standard errors for all estimates of covariate effects including metastatic effects under the above models were adjusted for the hospital to account for the increased variability due to clustering of individuals within hospitals. Two‐tailed P values <0.05 were considered statistically significant. Actual P values and 95% confidence intervals are reported. Data were analyzed using STATA, Version 10 (Stata Corporation, College Station, TX).
Results
Demographics
There were 2780 children admitted with bacterial meningitis during the study period; 461 (17%) children were excluded because of comorbid illness including malignancy (n = 37), congential heart disease (n = 231), prematurity (n = 104), human immunodeficiency virus infection (n = 4), sickle cell disease (n = 17), and post‐operative infection (n = 68). The remaining 2319 children with bacterial meningitis were included in the analyses. The mean age was 3.6 years (median, 1 year; IQR, 0‐6 years). Approximately half of the children were less than 1 year of age, 23% were 1 to 5 years, and 27% were >5 years. A total of 54% of children were white, 19% were black, 22% were Hispanic, and 5% were of other racial groups. Males accounted for 58% of the children. In this cohort of children, 9% received adjuvant corticosteroids within 24 hours of hospitalization.
Bacterial Meningitis‐Associated Conditions
Overall, 574 (25%) of children with bacterial meningitis suffered a systemic complication or an associated focal infection. Figure 1 shows the types of associated condition stratified by age category. Older children had a higher frequency of associated focal infections while younger children had a higher frequency of systemic complications (P = 0.002, chi‐square test for trend). Figure 2 shows the distribution of specific conditions among children in each age category. The frequency of sepsis decreased with age (P < 0.001, chi‐square test) while the frequency of mastoiditis (P < 0.001, Fisher's exact test) and osteomyelitis (P = 0.005, Fisher's exact test) increased with age. There did not appear to be substantial variability in the proportion of patients with SIRS or sepsis across hospitals, suggesting that hospital‐level variability in coding for these conditions was likely minimal. The median proportion of patients with SIRS by hospital was 2.4% (IQR, 1.2‐4.8%) while the median proportion of patients with sepsis by hospital was 13.4% (IQR, 10.0‐16.9%).
Of the 151 children with an associated focal infection, only 3 (2%) of children had more than 1 infection (1 child had mastoiditis and endocarditis, 1 child had pneumonia and osteomyelitis, and 1 child had pneumonia and endocarditis). However, of the 479 children with systemic complications, 116 (24%) had more than 1 systemic disease (Table 1).
| Types of Systemic Complications | Systemic Complications in All Bacterial Meningitis, n (%) | Systemic Complications in Meningococcal Meningitis, n (%) | Systemic Complications in Pneumococcal Meningitis, n (%) |
|---|---|---|---|
| |||
| Sepsis only | 209 (44) | 16 (21) | 69 (54) |
| Respiratory failure only | 139 (29) | 38 (49) | 30 (24) |
| SIRS only | 15 (3) | 9 (12) | 1 (1) |
| Sepsis and respiratory failure | 52 (11) | 4 (5) | 18 (14) |
| SIRS and sepsis | 27 (6) | 2 (3) | 4 (3) |
| SIRS and respiratory failure | 9 (2) | 5 (6) | 0 (0) |
| SIRS and respiratory failure and sepsis | 28 (6) | 3 (4) | 5 (4) |
| Total systemic complications | 479 | 77 | 127 |
In sub‐group analyses, 269 children had meningococcal meningitis and 470 children had pneumococcal meningitis. Of the children with meningococcal meningitis, 31.2% had a meningitis‐associated condition: 26.4% had a systemic complication, 2.6% had a focal infection, and 2.2% had both conditions. The most common associated conditions in children with meningococcal meningitis were respiratory failure (18.6%; n = 50), sepsis (9.3%; n = 25), and SIRS (7.1%; n = 19). In children with pneumococcal meningitis, 32.3% had a meningitis‐associated complication: 24.7% had a systemic complication, 5.3% had a focal infection, and 2.3% had both conditions. The most common associated conditions in children with pneumococcal meningitis were sepsis (20.4%; n = 96), respiratory failure (11.3%; n = 53), and pneumonia (4.7%; n = 22); mastoiditis was present in 2.3% (n = 11) of children with pneumococcal meningitis. Respiratory failure was more common in meningococcal meningitis (18.6%) than in pneumococcal meningitis (11.3%; P = 0.006). In contrast, sepsis was less common in meningococcal meningitis (9.3%) than in pneumococcal meningitis (20.4%; P < 0.001).
Hospital Charges
Overall, the median charges per hospital ranged from $20,158 to $53,823. In‐hospital charges for children with bacterial meningitis with and without any identified associated conditions are presented in Table 2. In multivariate analyses, the presence of systemic conditions, associated focal infections, or both conditions was independently associated with significantly higher total in‐hospital charges (Table 2). When conditions were considered individually, bone and joint infections (213% increase; 95% CI, 113‐260%), endocarditis (108% increase; 95% CI, 23‐258%), and pneumonia (107% increase; 95% CI, 58‐171%) were associated with the highest increases in total hospital charges (Figure 3). In contrast, SIRS and mastoiditis were not associated with higher hospital charges (Figure 3).
| Charges | LOS | |||
|---|---|---|---|---|
| Median, $ (IQR) | Adjusted Increase,* % (95% CI) | Median, days (IQR) | Adjusted Increase,* % (95% CI) | |
| ||||
| None (n = 1,745) | $27,110 (15,823‐48,307) | Reference** | 9 (6‐14) | Reference |
| Systemic (n = 423) | $66,690 (39,546136,756) | 136 (108269) | 14 (923) | 72 (5196) |
| Focal Infection (n = 95) | $58,016 (29,056125,813) | 118 (77168) | 13 (928) | 78 (40126) |
| Both (n = 56) | $130,744 (62,397299,288) | 351 (237503) | 21.5 (1245) | 211 (142303) |
LOS
The median LOS was 9 days (IQR, 6‐15 days); 5% of children had a LOS >42 days. Table 2 summarizes difference in LOS by the presence and absence of systemic conditions and focal infections. In multivariate analyses, the presence of systemic conditions, associated focal infections, or both conditions was independently associated with a significantly longer LOS (Table 2). When conditions were considered individually, endocarditis (152% increase; 95% CI, 60‐300%) and pneumonia (136% increase; 95% CI, 85‐201%) were associated with the greatest adjusted increases in LOS (Figure 4); only mastoiditis was not associated with an increased LOS compared with those without complications.
Discussion
To our knowledge, this is the first study to examine bacterial meningitis‐associated conditions in children and their impact on in‐hospital resource utilization. We found that 25% of the cohort of children with bacterial meningitis suffered from at least one focal infection or systemic complication. This represents a significant invasive disease burden among children with bacterial meningitis who do not have underlying comorbid conditions. Younger children were more likely to have systemic complications when compared with older children, specifically due to a higher frequency of sepsis in children <1 year. Older children were more likely to have an associated focal infection, specifically due to an increase in mastoiditis and osteomyelitis in children >1 year. Only 2% of children had more than 1 focal infection, while 24% of children had more than 1 systemic complication.
Importantly, the presence of a systemic complication in a child with bacterial meningitis increased their in‐hospital adjusted charges by 136%. The presence of a focal infection increased in‐hospital adjusted charges by 118%. A child with both a systemic complication and a focal infection and had a 351% increase in in‐hospital adjusted charges.
The presence of systemic complications or associated focal infections was significantly associated with higher in‐hospital charges and longer hospital LOS. Most individual meningitis‐associated conditions included in this study were associated with higher in‐hospital charges with the exception of SIRS and mastoiditis. All individual meningitis‐associated conditions were associated with a longer LOS except mastoiditis. This finding is not surprising as the LOS for children with mastoiditis is typically shorter than for children with bacterial meningitis. Glikich et al.14 reported a mean LOS of approximately 8 days for children with mastoiditis. As meningitis in the context of mastoiditis is likely caused by direct extension of infection, patients with meningitis and mastoiditis likely required extended hospitalization to treat meningitis rather than mastoiditis. In contrast, patients with meningitis occurring in the context of metastatic dissemination of infection (eg, endocarditis, pneumonia) often have hemodynamic instability requiring prolonged intensive care support.
A study of children with sepsis found that increasing severity of illness was associated with greater hospital resource utilization.15 Our study shows that this may also be true in children with bacterial meningitis. We found that in children with bacterial meningitis, having systemic complications or an associated focal infection was associated with greater in‐hospital resource utilization. This finding may therefore indicate greater in‐hospital morbidity among children with a bacterial meningitis‐associated condition. Since mortality rates for bacterial meningitis are low in children, in‐hospital morbidity may be a better indicator of disease burden.
Our data show that, in contrast to adults, bacterial meningitis in children is not typically associated with other focal infections. Some focal complications such as mastoiditis and osteomyelitis disproportionately affect older children. These complications are typically accompanied by overt clinical manifestations. Therefore, we believe that the evaluation for the presence of concomitant focal infections can be guided by clinical examination findings and that routine radiologic evaluation for focal complications may not be necessary. Additionally, focal infections tend to occur in the absence of concomitant systemic complications. Of the 151 children with at least 1 associated focal infection, only 37% had a systemic complication. Bacterial meningitis may lie on a continuum of invasive disease depending on the virulence factors of the invading pathogen as well as specific host factors. Understanding the epidemiology of these associated conditions can enhance our understanding of the pathogenesis of bacterial meningitis in children. Understanding why some children suffer from septicemia rather than bacteremia may help in developing novel therapeutics.
There are several limitations to our study. First, since we identified focal infections and systemic complications using billing charges and ICD‐9 discharge diagnosis codes, it was impossible to determine when these conditions represented true complications of bacterial meningitis and when they represented the primary source of infection. Therefore, some of our primary outcomes may represent the cause of meningitis rather than a direct complication. We attempted to minimize such misclassification by limiting the cohort to those with a primary discharge diagnosis of bacterial meningitis though such misclassification is still possible.
Second, the use of ICD‐9 codes to accurately identify systemic complications and associated focal infections is a potential limitation. For example, respiratory failure, defined as the requirement of endotracheal intubation in our study, may not capture children receiving non‐invasive mechanical ventilation (eg, bilevel positive airway pressure). If use of noninvasive ventilation strategies did not depend exclusively on illness severity, our study would underestimate the frequency of respiratory failure. Furthermore, there may be inconsistencies among pediatric physicians in coding conditions such as SIRS and sepsis. Even in the clinical setting, a uniform definition of SIRS and sepsis is problematic due to physiologic differences between adults and children of varying age groups.16 An international panel of pediatricians proposed age‐specific definitions for sepsis and SIRS, while acknowledging the paucity of evidence to support some of their recommendations.16 None of the proposed definitions could be applied using administrative data. Limitations in the use of ICD‐9 discharge diagnosis codes to identify children with bacterial meningitis were discussed previously.1
Third, only free‐standing children's hospitals were included in the analysis. It is likely that many children with uncomplicated bacterial meningitis are treated at community hospitals or smaller academic centers. Our study may overestimate the rate of bacterial meningitis‐associated focal infections and systemic complications since participating hospitals serve as regional referral centers. To address the potential for such referral bias, we repeated the analysis while restricting the cohort to those children who had a lumbar puncture performed at the treating facility. No difference in frequency of associated conditions or in‐hospital resource utilization was found between children transferred and children not transferred. Finally, the PHIS database reports billed charge data rather than cost data. Billed data may overestimate the actual economic impact of bacterial meningitis‐associated complications since payers often reimburse at lesser rates. Resource utilization may also vary widely between hospitals and geographic locations as previously shown.15
In conclusion, bacterial meningitis remains an important cause of morbidity in children. Systemic complications such as sepsis and respiratory failure are common. Respiratory failure occurred more commonly among patients with meningococcal meningitis while sepsis occurred more commonly among patients with pneumococcal meningitis. While focal complications are uncommon, children >5 years of age are more likely than younger children to have concomitant mastoiditis or osteomyelitis. The presence of both systemic and focal complications is associated with substantially greater resource utilization than either complication alone.
Dr. Shah had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the analysis. Study concept and design: Shah, Mongelluzzo; acquisition of data: Shah, Mohamad; analysis and interpretation of data: Mongelluzzo, Mohamad, Ten Have, Shah; drafting of the manuscript: Mongelluzzo; critical revision of the manuscript for important intellectual content: Mongelluzzo, Mohamad, Ten Have, Shah; statistical analysis: Shah, Mongelluzzo, Ten Have; obtained funding: Shah, Mongelluzzo; administrative, technical, or material support: Shah; study supervision: Shah.
Appendix
Diagnosis Codes:
Endocarditis: 421.0, 421.1, 421.9
Mastoiditis: 383.0, 383.1, 383.2, 383.8, 383.9
Osteomyelitis: 730.0, 730.1, 730.2, 730.3, 730.7, 730.8, 730.9
Septic arthritis: 711.0, 711.1, 711.2, 711.3, 711.4, 711.5, 711.6, 711.7, 711.8, 711.9
Sepsis: 038.0, 038.1, 038.2, 038.3, 038.4, 038.8, 038.9
Systemic Inflammatory Response Syndrome: 995.92
Pneumonia: 480.0, 480.1, 480.2, 480.3, 480.8, 480.9, 481, 482.0, 482.1, 482.2, 482.3, 482.4, 482.8, 482.9, 483.0, 483.1, 483.8, 484.1, 484.3, 484.5, 484.6, 484.7, 484.8, 485, 486
Procedure Codes:
Endotracheal Intubation: 96.04
- , , , .Corticosteroids and mortality in children with bacterial meningitis.JAMA.2008;299:2048–2055.
- , , , et al.Bacterial meningitis in the United States in 1995. Active surveillance team.N Engl J Med.1997;337:970–976.
- Progress toward elimination of Haemophilus influenzae type b disease among infants and children–United States, 1987–1995.MMWR Morb Mortal Wkly Rep.1996;45:901–906.
- , .Bacterial meningitis in children.Lancet.2003;361:2139–2148.
- , .Dexamethasone in adults with bacterial meningitis.N Engl J Med.2002;347:1549–1556.
- , .Dexamethasone and pneumococcal meningitis.Ann Intern Med.2004;141:327.
- , , , et al.Dexamethasone in Vietnamese adolescents and adults with bacterial meningitis.N Engl J Med.2007;357:2431–2440.
- , , , , .Bacterial meningitis in an urban area: etiologic study and prognostic factors.Infection.2007;35:406–413.
- , , .Clinical features and prognostic factors in childhood pneumococcal meningitis.J Microbiol Immunol Infect.2008;41:48–53.
- , , .Clinical presentation and prognostic factors of Streptococcus pneumoniae meningitis according to the focus of infection.BMC Infect Dis.2005;5:93.
- , .Trends in invasive pneumococcal disease‐associated hospitalizations.Clin Infect Dis.2006;42:e1–e5.
- , , .Managing meningococcal disease in the United States: Hospital case characteristics and costs by age.Value Health.2006;9:236–243.
- , , , , , .Population‐based analysis of meningococcal disease mortality in the United States: 1990–2002.Pediatr Infect Dis J.2006;25:191–194.
- , , , .A contemporary analysis of acute mastoiditis.Arch Otolaryngol Head Neck Surg.1996;122:135–139.
- , , .Patient and hospital correlates of clinical outcomes and resource utilization in severe pediatric sepsis.Pediatrics.2007;119:487–494.
- , , .International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics.Pediatr Crit Care Med.2005;6:2–8.
- , , , .Corticosteroids and mortality in children with bacterial meningitis.JAMA.2008;299:2048–2055.
- , , , et al.Bacterial meningitis in the United States in 1995. Active surveillance team.N Engl J Med.1997;337:970–976.
- Progress toward elimination of Haemophilus influenzae type b disease among infants and children–United States, 1987–1995.MMWR Morb Mortal Wkly Rep.1996;45:901–906.
- , .Bacterial meningitis in children.Lancet.2003;361:2139–2148.
- , .Dexamethasone in adults with bacterial meningitis.N Engl J Med.2002;347:1549–1556.
- , .Dexamethasone and pneumococcal meningitis.Ann Intern Med.2004;141:327.
- , , , et al.Dexamethasone in Vietnamese adolescents and adults with bacterial meningitis.N Engl J Med.2007;357:2431–2440.
- , , , , .Bacterial meningitis in an urban area: etiologic study and prognostic factors.Infection.2007;35:406–413.
- , , .Clinical features and prognostic factors in childhood pneumococcal meningitis.J Microbiol Immunol Infect.2008;41:48–53.
- , , .Clinical presentation and prognostic factors of Streptococcus pneumoniae meningitis according to the focus of infection.BMC Infect Dis.2005;5:93.
- , .Trends in invasive pneumococcal disease‐associated hospitalizations.Clin Infect Dis.2006;42:e1–e5.
- , , .Managing meningococcal disease in the United States: Hospital case characteristics and costs by age.Value Health.2006;9:236–243.
- , , , , , .Population‐based analysis of meningococcal disease mortality in the United States: 1990–2002.Pediatr Infect Dis J.2006;25:191–194.
- , , , .A contemporary analysis of acute mastoiditis.Arch Otolaryngol Head Neck Surg.1996;122:135–139.
- , , .Patient and hospital correlates of clinical outcomes and resource utilization in severe pediatric sepsis.Pediatrics.2007;119:487–494.
- , , .International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics.Pediatr Crit Care Med.2005;6:2–8.
Copyright © 2010 Society of Hospital Medicine
The way to a man's heart is through his liver
A 57‐year‐old man with Hepatitis B and C was scheduled for an outpatient computed tomography (CT)‐guided biopsy of the left lobe of the liver for grading and staging of his liver disease at an outside hospital. Complete metabolic profile (CMP), complete blood count (CBC) and international normalized ratio (INR) were performed and were normal. Following his liver biopsy, the patient became hypotensive and developed shock. He received fluid resuscitation. Clinical exam and an abdominal x‐ray failed to identify a hepatic or intraperitoneal source of bleeding to explain the cause of hypotension. A chest radiograph showed an enlarged cardiac silhouette with clear lung fields. An electrocardiogram (ECG) demonstrated (Figure 1) 1‐mm ST segment elevation in the anterior leads. An emergent echocardiogram showed a significant pericardial effusion with echocardiographic evidence of cardiac tamponade. The patient underwent emergent pericardiocentesis with removal of 400 mL of hemorrhagic fluid. The etiology of the hemorrhagic fluid was thought to be due to myocardial injury secondary to the liver biopsy. Subsequently, the histopathology of the liver biopsy reported (Figure 2) features suggestive of cirrhosis of the liver. Additional tissues from the biopsy included pericardium, myocardium and coronary artery. The patient was transferred to our institution for a cardiac catheterization and coronary angiogram to evaluate his coronary anatomy. The coronary angiogram was normal without any evidence of dye extravasation. A follow‐up echocardiogram and CT scan of the chest showed residual pericardial and pleural fluid. The remainder of the hospital stay was uneventful and he was discharged on day 7 in good condition. He was doing well a month later at the time of his follow‐up visit.0, 0
Discussion
Serious complications of liver biopsy occur in less than 1% of biopsied patients and include intraperitoneal1 or intrahepatic hemorrhage,2, 3 pneumothorax, hemothorax, hemobilia,1 and injury to the gall bladder, colon, kidney and lung. Other rare complications of percutaneous liver biopsy include biliary ascites, bile pleuritis, bile peritonitis, subcutaneous emphysema, pneumoperitoneum, subphrenic abscess, carcinoid crisis, anaphylaxis after biopsy of an echinococcal cyst, pancreatitis due to hemobilia, and breakage of the biopsy needle.1, 4, 5 Bleeding is more common in the elderly and in patients with cirrhosis and liver cancer.1, 6 The most common cause of shock in a patient after liver biopsy is hypovolemia from intrahepatic or intraperitoneal bleeding. The incidence of such complications may be higher than commonly appreciated as these complications are likely underreported.
Ultrasound (US)‐guided and CT‐guided techniques are 2 common methods for performing liver biopsy. US‐guided and CT‐guided liver biopsy each have their own benefits and limitations. The CT‐guided biopsy provides an excellent resolution of the liver architecture and is done from the epigastric region, but uses a static view. The US‐guided liver biopsy, on the other hand, is done from the mid‐axillary intercostal line and is performed with real‐time images.
Our patient's complication was presumably caused by accidental passage of the biopsy needle from the liver into the pericardium during respiratory movements. The coronary artery tissue was most likely not an epicardial vessel as supported by the normal angiogram without evidence of coronary artery perforation.
Our patient had an inadvertent biopsy of cardiac tissue during a liver biopsy resulting in a hemorrhagic pericardial effusion and tamponade. Cardiac tamponade as a complication of liver biopsy and intrathoracic percutaneous procedures has been described, although this has very rarely been reported.7, 8 Fortunately, the patient's coronary artery anatomy was normal and he did well without surgical intervention.
Unusual procedural complications are reported in the literature with the intention of increasing awareness and improving patient safety. Percutaneous liver biopsy is performed to stage and grade liver disease for assessment and treatment. However, as with any invasive procedure, there are potential risks and complications. In patients who present with hypotension and shock following liver biopsy, myocardial injury with cardiac tamponade should be considered in the differential diagnosis.
- , , , .Complications following percutaneous liver biopsy: a multicentre retrospective study on 68,276 biopsies.J Hepatol.1986;2:165–173.
- , , .Intrahepatic hematoma: a complication of percutaneous liver biopsy.Gastroenterology.1974;67:284–289.
- , , , et al.Intrahepatic hematoma resulting in obstructive jaundice. An unusual complication of liver biopsy.Gastroenterology.1978;74(1):124–127.
- , , , .Liver biopsy: its safety and complications as seen at a liver transplant center.Transplantation.1993;55:1087–1090.
- , .Bile peritonitis after liver biopsy: nonsurgical management of a patient with an acute abdomen: a case report with review of the literature.Am J Gastroenterol.1987;82:265–268.
- , .Outcome of patients hospitalized for complications after outpatient liver biopsy.Ann Intern Med.1993;118:96–98.
- , , .Unusual presentation and course of acute cardiac tamponade.J Cardiothorac Vasc Anesth.2007;21:712–714.
- , , .Cardiac tamponade following fine needle aspiration (FNA) of a mediastinal mass.Clin Radiol.1998;53(2):151–152.
A 57‐year‐old man with Hepatitis B and C was scheduled for an outpatient computed tomography (CT)‐guided biopsy of the left lobe of the liver for grading and staging of his liver disease at an outside hospital. Complete metabolic profile (CMP), complete blood count (CBC) and international normalized ratio (INR) were performed and were normal. Following his liver biopsy, the patient became hypotensive and developed shock. He received fluid resuscitation. Clinical exam and an abdominal x‐ray failed to identify a hepatic or intraperitoneal source of bleeding to explain the cause of hypotension. A chest radiograph showed an enlarged cardiac silhouette with clear lung fields. An electrocardiogram (ECG) demonstrated (Figure 1) 1‐mm ST segment elevation in the anterior leads. An emergent echocardiogram showed a significant pericardial effusion with echocardiographic evidence of cardiac tamponade. The patient underwent emergent pericardiocentesis with removal of 400 mL of hemorrhagic fluid. The etiology of the hemorrhagic fluid was thought to be due to myocardial injury secondary to the liver biopsy. Subsequently, the histopathology of the liver biopsy reported (Figure 2) features suggestive of cirrhosis of the liver. Additional tissues from the biopsy included pericardium, myocardium and coronary artery. The patient was transferred to our institution for a cardiac catheterization and coronary angiogram to evaluate his coronary anatomy. The coronary angiogram was normal without any evidence of dye extravasation. A follow‐up echocardiogram and CT scan of the chest showed residual pericardial and pleural fluid. The remainder of the hospital stay was uneventful and he was discharged on day 7 in good condition. He was doing well a month later at the time of his follow‐up visit.0, 0
Discussion
Serious complications of liver biopsy occur in less than 1% of biopsied patients and include intraperitoneal1 or intrahepatic hemorrhage,2, 3 pneumothorax, hemothorax, hemobilia,1 and injury to the gall bladder, colon, kidney and lung. Other rare complications of percutaneous liver biopsy include biliary ascites, bile pleuritis, bile peritonitis, subcutaneous emphysema, pneumoperitoneum, subphrenic abscess, carcinoid crisis, anaphylaxis after biopsy of an echinococcal cyst, pancreatitis due to hemobilia, and breakage of the biopsy needle.1, 4, 5 Bleeding is more common in the elderly and in patients with cirrhosis and liver cancer.1, 6 The most common cause of shock in a patient after liver biopsy is hypovolemia from intrahepatic or intraperitoneal bleeding. The incidence of such complications may be higher than commonly appreciated as these complications are likely underreported.
Ultrasound (US)‐guided and CT‐guided techniques are 2 common methods for performing liver biopsy. US‐guided and CT‐guided liver biopsy each have their own benefits and limitations. The CT‐guided biopsy provides an excellent resolution of the liver architecture and is done from the epigastric region, but uses a static view. The US‐guided liver biopsy, on the other hand, is done from the mid‐axillary intercostal line and is performed with real‐time images.
Our patient's complication was presumably caused by accidental passage of the biopsy needle from the liver into the pericardium during respiratory movements. The coronary artery tissue was most likely not an epicardial vessel as supported by the normal angiogram without evidence of coronary artery perforation.
Our patient had an inadvertent biopsy of cardiac tissue during a liver biopsy resulting in a hemorrhagic pericardial effusion and tamponade. Cardiac tamponade as a complication of liver biopsy and intrathoracic percutaneous procedures has been described, although this has very rarely been reported.7, 8 Fortunately, the patient's coronary artery anatomy was normal and he did well without surgical intervention.
Unusual procedural complications are reported in the literature with the intention of increasing awareness and improving patient safety. Percutaneous liver biopsy is performed to stage and grade liver disease for assessment and treatment. However, as with any invasive procedure, there are potential risks and complications. In patients who present with hypotension and shock following liver biopsy, myocardial injury with cardiac tamponade should be considered in the differential diagnosis.
A 57‐year‐old man with Hepatitis B and C was scheduled for an outpatient computed tomography (CT)‐guided biopsy of the left lobe of the liver for grading and staging of his liver disease at an outside hospital. Complete metabolic profile (CMP), complete blood count (CBC) and international normalized ratio (INR) were performed and were normal. Following his liver biopsy, the patient became hypotensive and developed shock. He received fluid resuscitation. Clinical exam and an abdominal x‐ray failed to identify a hepatic or intraperitoneal source of bleeding to explain the cause of hypotension. A chest radiograph showed an enlarged cardiac silhouette with clear lung fields. An electrocardiogram (ECG) demonstrated (Figure 1) 1‐mm ST segment elevation in the anterior leads. An emergent echocardiogram showed a significant pericardial effusion with echocardiographic evidence of cardiac tamponade. The patient underwent emergent pericardiocentesis with removal of 400 mL of hemorrhagic fluid. The etiology of the hemorrhagic fluid was thought to be due to myocardial injury secondary to the liver biopsy. Subsequently, the histopathology of the liver biopsy reported (Figure 2) features suggestive of cirrhosis of the liver. Additional tissues from the biopsy included pericardium, myocardium and coronary artery. The patient was transferred to our institution for a cardiac catheterization and coronary angiogram to evaluate his coronary anatomy. The coronary angiogram was normal without any evidence of dye extravasation. A follow‐up echocardiogram and CT scan of the chest showed residual pericardial and pleural fluid. The remainder of the hospital stay was uneventful and he was discharged on day 7 in good condition. He was doing well a month later at the time of his follow‐up visit.0, 0
Discussion
Serious complications of liver biopsy occur in less than 1% of biopsied patients and include intraperitoneal1 or intrahepatic hemorrhage,2, 3 pneumothorax, hemothorax, hemobilia,1 and injury to the gall bladder, colon, kidney and lung. Other rare complications of percutaneous liver biopsy include biliary ascites, bile pleuritis, bile peritonitis, subcutaneous emphysema, pneumoperitoneum, subphrenic abscess, carcinoid crisis, anaphylaxis after biopsy of an echinococcal cyst, pancreatitis due to hemobilia, and breakage of the biopsy needle.1, 4, 5 Bleeding is more common in the elderly and in patients with cirrhosis and liver cancer.1, 6 The most common cause of shock in a patient after liver biopsy is hypovolemia from intrahepatic or intraperitoneal bleeding. The incidence of such complications may be higher than commonly appreciated as these complications are likely underreported.
Ultrasound (US)‐guided and CT‐guided techniques are 2 common methods for performing liver biopsy. US‐guided and CT‐guided liver biopsy each have their own benefits and limitations. The CT‐guided biopsy provides an excellent resolution of the liver architecture and is done from the epigastric region, but uses a static view. The US‐guided liver biopsy, on the other hand, is done from the mid‐axillary intercostal line and is performed with real‐time images.
Our patient's complication was presumably caused by accidental passage of the biopsy needle from the liver into the pericardium during respiratory movements. The coronary artery tissue was most likely not an epicardial vessel as supported by the normal angiogram without evidence of coronary artery perforation.
Our patient had an inadvertent biopsy of cardiac tissue during a liver biopsy resulting in a hemorrhagic pericardial effusion and tamponade. Cardiac tamponade as a complication of liver biopsy and intrathoracic percutaneous procedures has been described, although this has very rarely been reported.7, 8 Fortunately, the patient's coronary artery anatomy was normal and he did well without surgical intervention.
Unusual procedural complications are reported in the literature with the intention of increasing awareness and improving patient safety. Percutaneous liver biopsy is performed to stage and grade liver disease for assessment and treatment. However, as with any invasive procedure, there are potential risks and complications. In patients who present with hypotension and shock following liver biopsy, myocardial injury with cardiac tamponade should be considered in the differential diagnosis.
- , , , .Complications following percutaneous liver biopsy: a multicentre retrospective study on 68,276 biopsies.J Hepatol.1986;2:165–173.
- , , .Intrahepatic hematoma: a complication of percutaneous liver biopsy.Gastroenterology.1974;67:284–289.
- , , , et al.Intrahepatic hematoma resulting in obstructive jaundice. An unusual complication of liver biopsy.Gastroenterology.1978;74(1):124–127.
- , , , .Liver biopsy: its safety and complications as seen at a liver transplant center.Transplantation.1993;55:1087–1090.
- , .Bile peritonitis after liver biopsy: nonsurgical management of a patient with an acute abdomen: a case report with review of the literature.Am J Gastroenterol.1987;82:265–268.
- , .Outcome of patients hospitalized for complications after outpatient liver biopsy.Ann Intern Med.1993;118:96–98.
- , , .Unusual presentation and course of acute cardiac tamponade.J Cardiothorac Vasc Anesth.2007;21:712–714.
- , , .Cardiac tamponade following fine needle aspiration (FNA) of a mediastinal mass.Clin Radiol.1998;53(2):151–152.
- , , , .Complications following percutaneous liver biopsy: a multicentre retrospective study on 68,276 biopsies.J Hepatol.1986;2:165–173.
- , , .Intrahepatic hematoma: a complication of percutaneous liver biopsy.Gastroenterology.1974;67:284–289.
- , , , et al.Intrahepatic hematoma resulting in obstructive jaundice. An unusual complication of liver biopsy.Gastroenterology.1978;74(1):124–127.
- , , , .Liver biopsy: its safety and complications as seen at a liver transplant center.Transplantation.1993;55:1087–1090.
- , .Bile peritonitis after liver biopsy: nonsurgical management of a patient with an acute abdomen: a case report with review of the literature.Am J Gastroenterol.1987;82:265–268.
- , .Outcome of patients hospitalized for complications after outpatient liver biopsy.Ann Intern Med.1993;118:96–98.
- , , .Unusual presentation and course of acute cardiac tamponade.J Cardiothorac Vasc Anesth.2007;21:712–714.
- , , .Cardiac tamponade following fine needle aspiration (FNA) of a mediastinal mass.Clin Radiol.1998;53(2):151–152.
Inappropriate Treatment of HCA‐cSSTI
Classically, infections have been categorized as either community‐acquired (CAI) or nosocomial in origin. Until recently, this scheme was thought adequate to capture the differences in the microbiology and outcomes in the corresponding scenarios. However, recent evidence suggests that this distinction may no longer be valid. For example, with the spread and diffusion of healthcare delivery beyond the confines of the hospital along with the increasing use of broad spectrum antibiotics both in and out of the hospital, pathogens such as methicillin‐resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PA), traditionally thought to be confined to the hospital, are now seen in patients presenting from the community to the emergency department (ED).1, 2 Reflecting this shift in epidemiology, some national guidelines now recognize healthcare‐associated infection (HCAI) as a distinct entity.3 The concept of HCAI allows the clinician to identify patients who, despite suffering a community onset infection, still may be at risk for a resistant bacterial pathogen. Recent studies in both bloodstream infection and pneumonia have clearly demonstrated that those with HCAI have distinct microbiology and outcomes relative to those with pure CAI.47
Most work focusing on establishing HCAI has not addressed skin and soft tissue infections. These infections, although not often fatal, account for an increasing number of admissions to the hospital.8, 9 In addition, they may be associated with substantial morbidity and cost.8 Given that many pathogens such as S. aureus, which may be resistant to typical antimicrobials used in the ED, are also major culprits in complicated skin and skin structure infections (cSSSI), the HCAI paradigm may apply in cSSSI. Furthermore, because of these patterns of increased resistance, HCA‐cSSSI patients, similar to other HCAI groups, may be at an increased risk of being treated with initially inappropriate antibiotic therapy.7, 10
Since in the setting of other types of infection inappropriate empiric treatment has been shown to be associated with increased mortality and costs,7, 1015 and since indirect evidence suggests a similar impact on healthcare utilization among cSSSI patients,8 we hypothesized that among a cohort of patients hospitalized with a cSSSI, the initial empiric choice of therapy is independently associated with hospital length of stay (LOS). We performed a retrospective cohort study to address this question.
Methods
Study Design
We performed a single‐center retrospective cohort study of patients with cSSSI admitted to the hospital through the ED. All consecutive patients hospitalized between April 2006 and December 2007 meeting predefined inclusion criteria (see below) were enrolled. The study was approved by the Washington University School of Medicine Human Studies Committee, and informed consent was waived. We have previously reported on the characteristics and outcomes of this cohort, including both community‐acquired and HCA‐cSSSI patients.16
Study Cohort
All consecutive patients admitted from the community through the ED between April 2006 and December 2007 at the Barnes‐Jewish Hospital, a 1200‐bed university‐affiliated, urban teaching hospital in St. Louis, MO were included if: (1) they had a diagnosis of a predefined cSSSI (see Appendix Table A1, based on reference 8) and (2) they had a positive microbiology culture obtained within 24 hours of hospital admission. Similar to the work by Edelsberg et al.8 we excluded patients if certain diagnoses and procedures were present (Appendix Table A2). Cases were also excluded if they represented a readmission for the same diagnosis within 30 days of the original hospitalization.
Definitions
HCAI was defined as any cSSSI in a patient with a history of recent hospitalization (within the previous year, consistent with the previous study16), receiving antibiotics prior to admission (previous 90 days), transferring from a nursing home, or needing chronic dialysis. We defined a polymicrobial infection as one with more than one organism, and mixed infection as an infection with both a gram‐positive and a gram‐negative organism. Inappropriate empiric therapy took place if a patient did not receive treatment within 24 hours of the time the culture was obtained with an agent exhibiting in vitro activity against the isolated pathogen(s). In mixed infections, appropriate therapy was treatment within 24 hours of culture being obtained with agent(s) active against all pathogens recovered.
Data Elements
We collected information about multiple baseline demographic and clinical factors including: age, gender, race/ethnicity, comorbidities, the presence of risk factors for HCAI, the presence of bacteremia at admission, and the location of admission (ward vs. intensive care unit [ICU]). Bacteriology data included information on specific bacterium/a recovered from culture, the site of the culture (eg, tissue, blood), susceptibility patterns, and whether the infection was monomicrobial, polymicrobial, or mixed. When blood culture was available and positive, we prioritized this over wound and other cultures and designated the corresponding organism as the culprit in the index infection. Cultures growing our coagulase‐negative S. aureus were excluded as a probable contaminant. Treatment data included information on the choice of the antimicrobial therapy and the timing of its institution relative to the timing of obtaining the culture specimen. The presence of such procedures as incision and drainage (I&D) or debridement was recorded.
Statistical Analyses
Descriptive statistics comparing HCAI patients treated appropriately to those receiving inappropriate empiric coverage based on their clinical, demographic, microbiologic and treatment characteristics were computed. Hospital LOS served as the primary and hospital mortality as the secondary outcomes, comparing patients with HCAI treated appropriately to those treated inappropriately. All continuous variables were compared using Student's t test or the Mann‐Whitney U test as appropriate. All categorical variables were compared using the chi‐square test or Fisher's exact test. To assess the attributable impact of inappropriate therapy in HCAI on the outcomes of interest, general linear models with log transformation were developed to model hospital LOS parameters; all means are presented as geometric means. All potential risk factors significant at the 0.1 level in univariate analyses were entered into the model. All calculations were performed in Stata version 9 (Statacorp, College Station, TX).
Results
Of the 717 patients with culture‐positive cSSSI admitted during the study period, 527 (73.5%) were classified as HCAI. The most common reason for classification as an HCAI was recent hospitalization. Among those with an HCA‐cSSSI, 405 (76.9%) received appropriate empiric treatment, with nearly one‐quarter receiving inappropriate initial coverage. Those receiving inappropriate antibiotic were more likely to be African American, and had a higher likelihood of having end‐stage renal disease (ESRD) than those with appropriate coverage (Table 1). While those patients treated appropriately had higher rates of both cellulitis and abscess as the presenting infection, a substantially higher proportion of those receiving inappropriate initial treatment had a decubitus ulcer (29.5% vs. 10.9%, P <0.001), a device‐associated infection (42.6% vs. 28.6%, P = 0.004), and had evidence of bacteremia (68.9% vs. 57.8%, P = 0.028) than those receiving appropriate empiric coverage (Table 2).
| Inappropriate (n = 122), n (%) | Appropriate (n = 405), n (%) | P Value | |
|---|---|---|---|
| |||
| Age, years | 56.3 18.0 | 53.6 16.7 | 0.147 |
| Gender (F) | 62 (50.8) | 190 (46.9) | 0.449 |
| Race | |||
| Caucasian | 51 (41.8) | 219 (54.1) | 0.048 |
| African American | 68 (55.7) | 178 (43.9) | |
| Other | 3 (2.5) | 8 (2.0) | |
| HCAI risk factors | |||
| Recent hospitalization* | 110 (90.2) | 373 (92.1) | 0.498 |
| Within 90 days | 98 (80.3) | 274 (67.7) | 0.007 |
| >90 and 180 days | 52 (42.6) | 170 (42.0) | 0.899 |
| >180 days and 1 year | 46 (37.7) | 164 (40.5) | 0.581 |
| Prior antibiotics | 26 (21.3) | 90 (22.2) | 0.831 |
| Nursing home resident | 29 (23.8) | 54 (13.3) | 0.006 |
| Hemodialysis | 19 (15.6) | 39 (9.7) | 0.067 |
| Comorbidities | |||
| DM | 40 (37.8) | 128 (31.6) | 0.806 |
| PVD | 5 (4.1) | 15 (3.7) | 0.841 |
| Liver disease | 6 (4.9) | 33 (8.2) | 0.232 |
| Cancer | 21 (17.2) | 85 (21.0) | 0.362 |
| HIV | 1 (0.8) | 12 (3.0) | 0.316 |
| Organ transplant | 2 (1.6) | 8 (2.0) | 1.000 |
| Autoimmune disease | 5 (4.1) | 8 (2.0) | 0.185 |
| ESRD | 22 (18.0) | 46 (11.4) | 0.054 |
| Inappropriate (n = 122), n (%) | Appropriate (n = 405), n (%) | P Value | |
|---|---|---|---|
| |||
| Cellulitis | 28 (23.0) | 171 (42.2) | <0.001 |
| Decubitus ulcer | 36 (29.5) | 44 (10.9) | <0.001 |
| Post‐op wound | 25 (20.5) | 75 (18.5) | 0.626 |
| Device‐associated infection | 52 (42.6) | 116 (28.6) | 0.004 |
| Diabetic foot ulcer | 9 (7.4) | 24 (5.9) | 0.562 |
| Abscess | 22 (18.0) | 108 (26.7) | 0.052 |
| Other* | 2 (1.6) | 17 (4.2) | 0.269 |
| Presence of bacteremia | 84 (68.9) | 234 (57.8) | 0.028 |
The pathogens recovered from the appropriately and inappropriately treated groups are listed in Figure 1. While S. aureus overall was more common among those treated appropriately, the frequency of MRSA did not differ between the groups. Both E. faecalis and E. faecium were recovered more frequently in the inappropriate group, resulting in a similar pattern among the vancomycin‐resistant enterococcal species. Likewise, P. aeruginosa, P. mirabilis, and A. baumannii were all more frequently seen in the group treated inappropriately than in the group getting appropriate empiric coverage. A mixed infection was also more likely to be present among those not exposed (16.5%) than among those exposed (7.5%) to appropriate early therapy (P = 0.001) (Figure 1).
In terms of processes of care and outcomes (Table 3), commensurate with the higher prevalence of abscess in the appropriately treated group, the rate of I&D was significantly higher in this cohort (36.8%) than in the inappropriately treated (23.0%) group (P = 0.005). Need for initial ICU care did not differ as a function of appropriateness of therapy (P = 0.635).
| Inappropriate (n = 122) | Appropriate (n = 405) | P Value | |
|---|---|---|---|
| |||
| I&D/debridement | 28 (23.0%) | 149 (36.8%) | 0.005 |
| I&D in ED | 0 | 7 (1.7) | 0.361 |
| ICU | 9 (7.4%) | 25 (6.2%) | 0.635 |
| Hospital LOS, days | |||
| Median (IQR 25, 75) [Range] | 7.0 (4.2, 13.6) [0.686.6] | 6 (3.3, 10.1) [0.748.3] | 0.026 |
| Hospital mortality | 9 (7.4%) | 26 (6.4%) | 0.710 |
The unadjusted mortality rate was low overall and did not vary based on initial treatment (Table 3). In a generalized linear model with the log‐transformed LOS as the dependent variable, adjusting for multiple potential confounders, initial inappropriate antibiotic therapy had an attributable incremental increase in the hospital LOS of 1.8 days (95% CI, 1.42.3) (Table 4).
| Factor | Attributable LOS (days) | 95% CI | P Value |
|---|---|---|---|
| |||
| Infection type: device | 3.6 | 2.74.8 | <0.001 |
| Infection type: decubitus ulcer | 3.3 | 2.64.2 | <0.001 |
| Infection type: abscess | 2.5 | 1.64.0 | <0.001 |
| Organism: P. mirabilis | 2.2 | 1.43.4 | <0.001 |
| Organism: E. faecalis | 2.1 | 1.72.6 | <0.001 |
| Nursing home resident | 2.1 | 1.62.6 | <0.001 |
| Inappropriate antibiotic | 1.8 | 1.42.3 | <0.001 |
| Race: Non‐Caucasian | 0.31 | 0.240.41 | <0.001 |
| Organism: E. faecium | 0.23 | 0.150.35 | <0.001 |
Because bacteremia is known to be an effect modifier of the relationship between the empiric choice of antibiotic and infection outcomes, we further explored its role in the HCAI cSSSI on the outcomes of interest (Table 5). Similar to the effect detected in the overall cohort, treatment with inappropriate therapy was associated with an increase in the hospital LOS, but not hospital mortality in those with bacteremia, though this phenomenon was observed only among patients with secondary bacteremia, and not among those without (Table 5).
| Bacteremia Present (n = 318) | Bacteremia Absent (n = 209) | |||||
|---|---|---|---|---|---|---|
| I (n = 84) | A (n = 234) | P Value | I (n = 38) | A (n = 171) | P Value | |
| ||||||
| Hospital LOS, days | ||||||
| Mean SD | 14.4 27.5 | 9.8 9.7 | 0.041 | 6.6 6.8 | 6.9 8.2 | 0.761 |
| Median (IQR 25, 75) | 8.8 (5.4, 13.9) | 7.0 (4.3, 11.7) | 4.4 (2.4, 7.7) | 3.9 (2.0, 8.2) | ||
| Hospital mortality | 8 (9.5%) | 24 (10.3%) | 0.848 | 1 (2.6%) | 2 (1.2%) | 0.454 |
Discussion
This retrospective analysis provides evidence that inappropriate empiric antibiotic therapy for HCA‐cSSSI independently prolongs hospital LOS. The impact of inappropriate initial treatment on LOS is independent of many important confounders. In addition, we observed that this effect, while present among patients with secondary bacteremia, is absent among those without a blood stream infection.
To the best of our knowledge, ours is the first cohort study to examine the outcomes associated with inappropriate treatment of a HCAI cSSSI within the context of available microbiology data. Edelsberg et al.8 examined clinical and economic outcomes associated with the failure of the initial treatment of cSSSI. While not specifically focusing on HCAI patients, these authors noted an overall 23% initial therapy failure rate. Among those patients who failed initial therapy, the risk of hospital death was nearly 3‐fold higher (adjusted odds ratio [OR], 2.91; 95% CI, 2.343.62), and they incurred the mean of 5.4 additional hospital days, compared to patients treated successfully with the initial regimen.8 Our study confirms Edelsberg et al.'s8 observation of prolonged hospital LOS in association with treatment failure, and builds upon it by defining the actual LOS increment attributable to inappropriate empiric therapy. It is worth noting that the study by Edelsberg et al.,8 however, lacked explicit definition of the HCAI population and microbiology data, and used treatment failure as a surrogate marker for inappropriate treatment. It is likely these differences between our two studies in the underlying population and exposure definitions that account for the differences in the mortality data between that study and ours.
It is not fundamentally surprising that early exposure to inappropriate empiric therapy alters healthcare resource utilization outcomes for the worse. Others have demonstrated that infection with a resistant organism results in prolongation of hospital LOS and costs. For example, in a large cohort of over 600 surgical hospitalizations requiring treatment for a gram‐negative infection, antibiotic resistance was an independent predictor of increased LOS and costs.15 These authors quantified the incremental burden of early gram‐negative resistance at over $11,000 in hospital costs.15 Unfortunately, the treatment differences for resistant and sensitive organisms were not examined.15 Similarly, Shorr et al. examined risk factors for prolonged hospital LOS and increased costs in a cohort of 291 patients with MRSA sterile site infection.17 Because in this study 23% of the patients received inappropriate empiric therapy, the authors were able to examine the impact of this exposure on utilization outcomes.17 In an adjusted analysis, inappropriate initial treatment was associated with an incremental increase in the LOS of 2.5 days, corresponding to the unadjusted cost differential of nearly $6,000.17 Although focusing on a different population, our results are consistent with these previous observations that antibiotic resistance and early inappropriate therapy affect hospital utilization parameters, in our case by adding nearly 2 days to the hospital LOS.
Our study has a number of limitations. First, as a retrospective cohort study it is prone to various forms of bias, most notably selection bias. To minimize the possibility of such, we established a priori case definitions and enrolled consecutive patients over a specific period of time. Second, as in any observational study, confounding is an issue. We dealt with this statistically by constructing a multivariable regression model; however, the possibility of residual confounding remains. Third, because some of the wound and ulcer cultures likely were obtained with a swab and thus represented colonization, rather than infection, we may have over‐estimated the rate of inappropriate therapy, and this needs to be followed up in future prospective studies. Similarly, we may have over‐estimated the likelihood of inappropriate therapy among polymicrobial and mixed infections as well, given that, for example, a gram‐negative organism may carry a different clinical significance when cultured from blood (infection) than when it is detected in a decubitus ulcer (potential colonization). Fourth, because we limited our cohort to patients without deep‐seated infections, such as necrotizing fasciitis, other procedures were not collected. This omission may have led to either over‐estimation or under‐estimation of the impact of inappropriate therapy on the outcomes of interest.
The fact that our cohort represents a single large urban academic tertiary care medical center may limit the generalizability of our results only to centers that share similar characteristics. Finally, similar to most other studies of this type, ours lacks data on posthospitalization outcomes and for this reason limits itself to hospital outcomes only.
In summary, we have shown that, similar to other populations with HCAI, a substantial proportion (nearly 1/4) of cSSSI patients with HCAI receive inappropriate empiric therapy for their infection, and this early exposure, though not affecting hospital mortality, is associated with a significant prolongation of the hospitalization by as much as 2 days. Studies are needed to refine decision rules for risk‐stratifying patients with cSSSI HCAI in order to determine the probability of infection with a resistant organism. In turn, such instruments at the bedside may assure improved utilization of appropriately targeted empiric therapy that will both optimize individual patient outcomes and reduce the risk of emergence of antimicrobial resistance.
Appendix
| Principal diagnosis code | Description |
|---|---|
| 680 | Carbuncle and furuncle |
| 681 | Cellulitis and abscess of finger and toe |
| 682 | Other cellulitis and abscess |
| 683 | Acute lymphadenitis |
| 685 | Pilonidal cyst with abscess |
| 686 | Other local infections of skin and subcutaneous tissue |
| 707 | Decubitus ulcer |
| 707.1 | Ulcers of lower limbs, except decubitus |
| 707.8 | Chronic ulcer of other specified sites |
| 707.9 | Chronic ulcer of unspecified site |
| 958.3 | Posttraumatic wound infection, not elsewhere classified |
| 996.62 | Infection due to other vascular device, implant, and graft |
| 997.62 | Infection (chronic) of amputation stump |
| 998.5 | Postoperative wound infection |
| Diagnosis code | Description |
|---|---|
| 728.86 | Necrotizing fasciitis |
| 785.4 | Gangrene |
| 686.09 | Ecthyma gangrenosum |
| 730.00730.2 | Osteomyelitis |
| 630677 | Complications of pregnancy, childbirth and puerperium |
| 288.0 | Neutropenia |
| 684 | Impetigo |
| Procedure code | |
| 39.95 | Plasmapheresis |
| 99.71 | Hemoperfusion |
- ,,, et al.Invasive methicillin‐resistant Staphylococcus aureus infections in the United States.JAMA.2007;298:1762–1771.
- ,,, et al.Methicillin‐resistant S. aureus infections among patients in the emergency department.N Engl J Med.2006;17;355:666–674.
- Hospital‐Acquired Pneumonia Guideline Committee of the American Thoracic Society and Infectious Diseases Society of America.Guidelines for the management of adults with hospital‐acquired pneumonia, ventilator‐associated pneumonia, and healthcare‐associated pneumonia.Am J Respir Crit Care Med.2005;171:388–416.
- ,,, et al.Epidemiology and outcomes of health‐care‐associated pneumonia: Results from a large US database of culture‐positive pneumonia.Chest.2005;128:3854–3862.
- ,,, et al.Health care‐associated bloodstream infections in adults: A reason to change the accepted definition of community‐acquired infections.Ann Intern Med.2002;137:791–797.
- ,,,,,.Healthcare‐associated bloodstream infection: A distinct entity? Insights from a large U.S. database.Crit Care Med.2006;34:2588–2595.
- ,,, et al.Health care‐associated pneumonia and community‐acquired pneumonia: a single‐center experience.Antimicrob Agents Chemother.2007;51:3568–3573.
- ,,,,,.Clinical and economic consequences of failure of initial antibiotic therapy for hospitalized patients with complicated skin and skin‐structure infections.Infect Control Hosp Epidemiol.2008;29:160–169.
- ,,, et al.Skin, soft tissue, bone, and joint infections in hospitalized patients: Epidemiology and microbiological, clinical, and economic outcomes.Infect Control Hosp Epidemiol.2007;28:1290–1298.
- ,,, et al.Methicillin‐resistant Staphylococcus aureus sterile‐site infection: The importance of appropriate initial antimicrobial treatment.Crit Care Med.2006;34:2069–2074.
- ,,, et al.The influence of inadequate antimicrobial treatment of bloodstream infections on patient outcomes in the ICU setting.Chest.2000;118:146–155.
- ,.Modification of empiric antibiotic treatment in patients with pneumonia acquired in the intensive care unit.Intensive Care Med.1996;22:387–394.
- ,,, et al.Clinical importance of delays in the initiation of appropriate antibiotic treatment for ventilator‐associated pneumonia.Chest.2002;122:262–268.
- ,,,,.Antimicrobial therapy escalation and hospital mortality among patients with HCAP: A single center experience.Chest.2008;134:963–968.
- ,,, et al.Cost of gram‐negative resistance.Crit Care Med.2007;35:89–95.
- ,,, et al.Epidemiology and outcomes of hospitalizations with complicated skin and skin‐structure infections: implications of healthcare‐associated infection risk factors.Infect Control Hosp Epidemiol.2009;30:1203–1210.
- ,,.Inappropriate therapy for methicillin‐resistant Staphylococcus aureus: resource utilization and cost implications.Crit Care Med.2008;36:2335–2340.
Classically, infections have been categorized as either community‐acquired (CAI) or nosocomial in origin. Until recently, this scheme was thought adequate to capture the differences in the microbiology and outcomes in the corresponding scenarios. However, recent evidence suggests that this distinction may no longer be valid. For example, with the spread and diffusion of healthcare delivery beyond the confines of the hospital along with the increasing use of broad spectrum antibiotics both in and out of the hospital, pathogens such as methicillin‐resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PA), traditionally thought to be confined to the hospital, are now seen in patients presenting from the community to the emergency department (ED).1, 2 Reflecting this shift in epidemiology, some national guidelines now recognize healthcare‐associated infection (HCAI) as a distinct entity.3 The concept of HCAI allows the clinician to identify patients who, despite suffering a community onset infection, still may be at risk for a resistant bacterial pathogen. Recent studies in both bloodstream infection and pneumonia have clearly demonstrated that those with HCAI have distinct microbiology and outcomes relative to those with pure CAI.47
Most work focusing on establishing HCAI has not addressed skin and soft tissue infections. These infections, although not often fatal, account for an increasing number of admissions to the hospital.8, 9 In addition, they may be associated with substantial morbidity and cost.8 Given that many pathogens such as S. aureus, which may be resistant to typical antimicrobials used in the ED, are also major culprits in complicated skin and skin structure infections (cSSSI), the HCAI paradigm may apply in cSSSI. Furthermore, because of these patterns of increased resistance, HCA‐cSSSI patients, similar to other HCAI groups, may be at an increased risk of being treated with initially inappropriate antibiotic therapy.7, 10
Since in the setting of other types of infection inappropriate empiric treatment has been shown to be associated with increased mortality and costs,7, 1015 and since indirect evidence suggests a similar impact on healthcare utilization among cSSSI patients,8 we hypothesized that among a cohort of patients hospitalized with a cSSSI, the initial empiric choice of therapy is independently associated with hospital length of stay (LOS). We performed a retrospective cohort study to address this question.
Methods
Study Design
We performed a single‐center retrospective cohort study of patients with cSSSI admitted to the hospital through the ED. All consecutive patients hospitalized between April 2006 and December 2007 meeting predefined inclusion criteria (see below) were enrolled. The study was approved by the Washington University School of Medicine Human Studies Committee, and informed consent was waived. We have previously reported on the characteristics and outcomes of this cohort, including both community‐acquired and HCA‐cSSSI patients.16
Study Cohort
All consecutive patients admitted from the community through the ED between April 2006 and December 2007 at the Barnes‐Jewish Hospital, a 1200‐bed university‐affiliated, urban teaching hospital in St. Louis, MO were included if: (1) they had a diagnosis of a predefined cSSSI (see Appendix Table A1, based on reference 8) and (2) they had a positive microbiology culture obtained within 24 hours of hospital admission. Similar to the work by Edelsberg et al.8 we excluded patients if certain diagnoses and procedures were present (Appendix Table A2). Cases were also excluded if they represented a readmission for the same diagnosis within 30 days of the original hospitalization.
Definitions
HCAI was defined as any cSSSI in a patient with a history of recent hospitalization (within the previous year, consistent with the previous study16), receiving antibiotics prior to admission (previous 90 days), transferring from a nursing home, or needing chronic dialysis. We defined a polymicrobial infection as one with more than one organism, and mixed infection as an infection with both a gram‐positive and a gram‐negative organism. Inappropriate empiric therapy took place if a patient did not receive treatment within 24 hours of the time the culture was obtained with an agent exhibiting in vitro activity against the isolated pathogen(s). In mixed infections, appropriate therapy was treatment within 24 hours of culture being obtained with agent(s) active against all pathogens recovered.
Data Elements
We collected information about multiple baseline demographic and clinical factors including: age, gender, race/ethnicity, comorbidities, the presence of risk factors for HCAI, the presence of bacteremia at admission, and the location of admission (ward vs. intensive care unit [ICU]). Bacteriology data included information on specific bacterium/a recovered from culture, the site of the culture (eg, tissue, blood), susceptibility patterns, and whether the infection was monomicrobial, polymicrobial, or mixed. When blood culture was available and positive, we prioritized this over wound and other cultures and designated the corresponding organism as the culprit in the index infection. Cultures growing our coagulase‐negative S. aureus were excluded as a probable contaminant. Treatment data included information on the choice of the antimicrobial therapy and the timing of its institution relative to the timing of obtaining the culture specimen. The presence of such procedures as incision and drainage (I&D) or debridement was recorded.
Statistical Analyses
Descriptive statistics comparing HCAI patients treated appropriately to those receiving inappropriate empiric coverage based on their clinical, demographic, microbiologic and treatment characteristics were computed. Hospital LOS served as the primary and hospital mortality as the secondary outcomes, comparing patients with HCAI treated appropriately to those treated inappropriately. All continuous variables were compared using Student's t test or the Mann‐Whitney U test as appropriate. All categorical variables were compared using the chi‐square test or Fisher's exact test. To assess the attributable impact of inappropriate therapy in HCAI on the outcomes of interest, general linear models with log transformation were developed to model hospital LOS parameters; all means are presented as geometric means. All potential risk factors significant at the 0.1 level in univariate analyses were entered into the model. All calculations were performed in Stata version 9 (Statacorp, College Station, TX).
Results
Of the 717 patients with culture‐positive cSSSI admitted during the study period, 527 (73.5%) were classified as HCAI. The most common reason for classification as an HCAI was recent hospitalization. Among those with an HCA‐cSSSI, 405 (76.9%) received appropriate empiric treatment, with nearly one‐quarter receiving inappropriate initial coverage. Those receiving inappropriate antibiotic were more likely to be African American, and had a higher likelihood of having end‐stage renal disease (ESRD) than those with appropriate coverage (Table 1). While those patients treated appropriately had higher rates of both cellulitis and abscess as the presenting infection, a substantially higher proportion of those receiving inappropriate initial treatment had a decubitus ulcer (29.5% vs. 10.9%, P <0.001), a device‐associated infection (42.6% vs. 28.6%, P = 0.004), and had evidence of bacteremia (68.9% vs. 57.8%, P = 0.028) than those receiving appropriate empiric coverage (Table 2).
| Inappropriate (n = 122), n (%) | Appropriate (n = 405), n (%) | P Value | |
|---|---|---|---|
| |||
| Age, years | 56.3 18.0 | 53.6 16.7 | 0.147 |
| Gender (F) | 62 (50.8) | 190 (46.9) | 0.449 |
| Race | |||
| Caucasian | 51 (41.8) | 219 (54.1) | 0.048 |
| African American | 68 (55.7) | 178 (43.9) | |
| Other | 3 (2.5) | 8 (2.0) | |
| HCAI risk factors | |||
| Recent hospitalization* | 110 (90.2) | 373 (92.1) | 0.498 |
| Within 90 days | 98 (80.3) | 274 (67.7) | 0.007 |
| >90 and 180 days | 52 (42.6) | 170 (42.0) | 0.899 |
| >180 days and 1 year | 46 (37.7) | 164 (40.5) | 0.581 |
| Prior antibiotics | 26 (21.3) | 90 (22.2) | 0.831 |
| Nursing home resident | 29 (23.8) | 54 (13.3) | 0.006 |
| Hemodialysis | 19 (15.6) | 39 (9.7) | 0.067 |
| Comorbidities | |||
| DM | 40 (37.8) | 128 (31.6) | 0.806 |
| PVD | 5 (4.1) | 15 (3.7) | 0.841 |
| Liver disease | 6 (4.9) | 33 (8.2) | 0.232 |
| Cancer | 21 (17.2) | 85 (21.0) | 0.362 |
| HIV | 1 (0.8) | 12 (3.0) | 0.316 |
| Organ transplant | 2 (1.6) | 8 (2.0) | 1.000 |
| Autoimmune disease | 5 (4.1) | 8 (2.0) | 0.185 |
| ESRD | 22 (18.0) | 46 (11.4) | 0.054 |
| Inappropriate (n = 122), n (%) | Appropriate (n = 405), n (%) | P Value | |
|---|---|---|---|
| |||
| Cellulitis | 28 (23.0) | 171 (42.2) | <0.001 |
| Decubitus ulcer | 36 (29.5) | 44 (10.9) | <0.001 |
| Post‐op wound | 25 (20.5) | 75 (18.5) | 0.626 |
| Device‐associated infection | 52 (42.6) | 116 (28.6) | 0.004 |
| Diabetic foot ulcer | 9 (7.4) | 24 (5.9) | 0.562 |
| Abscess | 22 (18.0) | 108 (26.7) | 0.052 |
| Other* | 2 (1.6) | 17 (4.2) | 0.269 |
| Presence of bacteremia | 84 (68.9) | 234 (57.8) | 0.028 |
The pathogens recovered from the appropriately and inappropriately treated groups are listed in Figure 1. While S. aureus overall was more common among those treated appropriately, the frequency of MRSA did not differ between the groups. Both E. faecalis and E. faecium were recovered more frequently in the inappropriate group, resulting in a similar pattern among the vancomycin‐resistant enterococcal species. Likewise, P. aeruginosa, P. mirabilis, and A. baumannii were all more frequently seen in the group treated inappropriately than in the group getting appropriate empiric coverage. A mixed infection was also more likely to be present among those not exposed (16.5%) than among those exposed (7.5%) to appropriate early therapy (P = 0.001) (Figure 1).
In terms of processes of care and outcomes (Table 3), commensurate with the higher prevalence of abscess in the appropriately treated group, the rate of I&D was significantly higher in this cohort (36.8%) than in the inappropriately treated (23.0%) group (P = 0.005). Need for initial ICU care did not differ as a function of appropriateness of therapy (P = 0.635).
| Inappropriate (n = 122) | Appropriate (n = 405) | P Value | |
|---|---|---|---|
| |||
| I&D/debridement | 28 (23.0%) | 149 (36.8%) | 0.005 |
| I&D in ED | 0 | 7 (1.7) | 0.361 |
| ICU | 9 (7.4%) | 25 (6.2%) | 0.635 |
| Hospital LOS, days | |||
| Median (IQR 25, 75) [Range] | 7.0 (4.2, 13.6) [0.686.6] | 6 (3.3, 10.1) [0.748.3] | 0.026 |
| Hospital mortality | 9 (7.4%) | 26 (6.4%) | 0.710 |
The unadjusted mortality rate was low overall and did not vary based on initial treatment (Table 3). In a generalized linear model with the log‐transformed LOS as the dependent variable, adjusting for multiple potential confounders, initial inappropriate antibiotic therapy had an attributable incremental increase in the hospital LOS of 1.8 days (95% CI, 1.42.3) (Table 4).
| Factor | Attributable LOS (days) | 95% CI | P Value |
|---|---|---|---|
| |||
| Infection type: device | 3.6 | 2.74.8 | <0.001 |
| Infection type: decubitus ulcer | 3.3 | 2.64.2 | <0.001 |
| Infection type: abscess | 2.5 | 1.64.0 | <0.001 |
| Organism: P. mirabilis | 2.2 | 1.43.4 | <0.001 |
| Organism: E. faecalis | 2.1 | 1.72.6 | <0.001 |
| Nursing home resident | 2.1 | 1.62.6 | <0.001 |
| Inappropriate antibiotic | 1.8 | 1.42.3 | <0.001 |
| Race: Non‐Caucasian | 0.31 | 0.240.41 | <0.001 |
| Organism: E. faecium | 0.23 | 0.150.35 | <0.001 |
Because bacteremia is known to be an effect modifier of the relationship between the empiric choice of antibiotic and infection outcomes, we further explored its role in the HCAI cSSSI on the outcomes of interest (Table 5). Similar to the effect detected in the overall cohort, treatment with inappropriate therapy was associated with an increase in the hospital LOS, but not hospital mortality in those with bacteremia, though this phenomenon was observed only among patients with secondary bacteremia, and not among those without (Table 5).
| Bacteremia Present (n = 318) | Bacteremia Absent (n = 209) | |||||
|---|---|---|---|---|---|---|
| I (n = 84) | A (n = 234) | P Value | I (n = 38) | A (n = 171) | P Value | |
| ||||||
| Hospital LOS, days | ||||||
| Mean SD | 14.4 27.5 | 9.8 9.7 | 0.041 | 6.6 6.8 | 6.9 8.2 | 0.761 |
| Median (IQR 25, 75) | 8.8 (5.4, 13.9) | 7.0 (4.3, 11.7) | 4.4 (2.4, 7.7) | 3.9 (2.0, 8.2) | ||
| Hospital mortality | 8 (9.5%) | 24 (10.3%) | 0.848 | 1 (2.6%) | 2 (1.2%) | 0.454 |
Discussion
This retrospective analysis provides evidence that inappropriate empiric antibiotic therapy for HCA‐cSSSI independently prolongs hospital LOS. The impact of inappropriate initial treatment on LOS is independent of many important confounders. In addition, we observed that this effect, while present among patients with secondary bacteremia, is absent among those without a blood stream infection.
To the best of our knowledge, ours is the first cohort study to examine the outcomes associated with inappropriate treatment of a HCAI cSSSI within the context of available microbiology data. Edelsberg et al.8 examined clinical and economic outcomes associated with the failure of the initial treatment of cSSSI. While not specifically focusing on HCAI patients, these authors noted an overall 23% initial therapy failure rate. Among those patients who failed initial therapy, the risk of hospital death was nearly 3‐fold higher (adjusted odds ratio [OR], 2.91; 95% CI, 2.343.62), and they incurred the mean of 5.4 additional hospital days, compared to patients treated successfully with the initial regimen.8 Our study confirms Edelsberg et al.'s8 observation of prolonged hospital LOS in association with treatment failure, and builds upon it by defining the actual LOS increment attributable to inappropriate empiric therapy. It is worth noting that the study by Edelsberg et al.,8 however, lacked explicit definition of the HCAI population and microbiology data, and used treatment failure as a surrogate marker for inappropriate treatment. It is likely these differences between our two studies in the underlying population and exposure definitions that account for the differences in the mortality data between that study and ours.
It is not fundamentally surprising that early exposure to inappropriate empiric therapy alters healthcare resource utilization outcomes for the worse. Others have demonstrated that infection with a resistant organism results in prolongation of hospital LOS and costs. For example, in a large cohort of over 600 surgical hospitalizations requiring treatment for a gram‐negative infection, antibiotic resistance was an independent predictor of increased LOS and costs.15 These authors quantified the incremental burden of early gram‐negative resistance at over $11,000 in hospital costs.15 Unfortunately, the treatment differences for resistant and sensitive organisms were not examined.15 Similarly, Shorr et al. examined risk factors for prolonged hospital LOS and increased costs in a cohort of 291 patients with MRSA sterile site infection.17 Because in this study 23% of the patients received inappropriate empiric therapy, the authors were able to examine the impact of this exposure on utilization outcomes.17 In an adjusted analysis, inappropriate initial treatment was associated with an incremental increase in the LOS of 2.5 days, corresponding to the unadjusted cost differential of nearly $6,000.17 Although focusing on a different population, our results are consistent with these previous observations that antibiotic resistance and early inappropriate therapy affect hospital utilization parameters, in our case by adding nearly 2 days to the hospital LOS.
Our study has a number of limitations. First, as a retrospective cohort study it is prone to various forms of bias, most notably selection bias. To minimize the possibility of such, we established a priori case definitions and enrolled consecutive patients over a specific period of time. Second, as in any observational study, confounding is an issue. We dealt with this statistically by constructing a multivariable regression model; however, the possibility of residual confounding remains. Third, because some of the wound and ulcer cultures likely were obtained with a swab and thus represented colonization, rather than infection, we may have over‐estimated the rate of inappropriate therapy, and this needs to be followed up in future prospective studies. Similarly, we may have over‐estimated the likelihood of inappropriate therapy among polymicrobial and mixed infections as well, given that, for example, a gram‐negative organism may carry a different clinical significance when cultured from blood (infection) than when it is detected in a decubitus ulcer (potential colonization). Fourth, because we limited our cohort to patients without deep‐seated infections, such as necrotizing fasciitis, other procedures were not collected. This omission may have led to either over‐estimation or under‐estimation of the impact of inappropriate therapy on the outcomes of interest.
The fact that our cohort represents a single large urban academic tertiary care medical center may limit the generalizability of our results only to centers that share similar characteristics. Finally, similar to most other studies of this type, ours lacks data on posthospitalization outcomes and for this reason limits itself to hospital outcomes only.
In summary, we have shown that, similar to other populations with HCAI, a substantial proportion (nearly 1/4) of cSSSI patients with HCAI receive inappropriate empiric therapy for their infection, and this early exposure, though not affecting hospital mortality, is associated with a significant prolongation of the hospitalization by as much as 2 days. Studies are needed to refine decision rules for risk‐stratifying patients with cSSSI HCAI in order to determine the probability of infection with a resistant organism. In turn, such instruments at the bedside may assure improved utilization of appropriately targeted empiric therapy that will both optimize individual patient outcomes and reduce the risk of emergence of antimicrobial resistance.
Appendix
| Principal diagnosis code | Description |
|---|---|
| 680 | Carbuncle and furuncle |
| 681 | Cellulitis and abscess of finger and toe |
| 682 | Other cellulitis and abscess |
| 683 | Acute lymphadenitis |
| 685 | Pilonidal cyst with abscess |
| 686 | Other local infections of skin and subcutaneous tissue |
| 707 | Decubitus ulcer |
| 707.1 | Ulcers of lower limbs, except decubitus |
| 707.8 | Chronic ulcer of other specified sites |
| 707.9 | Chronic ulcer of unspecified site |
| 958.3 | Posttraumatic wound infection, not elsewhere classified |
| 996.62 | Infection due to other vascular device, implant, and graft |
| 997.62 | Infection (chronic) of amputation stump |
| 998.5 | Postoperative wound infection |
| Diagnosis code | Description |
|---|---|
| 728.86 | Necrotizing fasciitis |
| 785.4 | Gangrene |
| 686.09 | Ecthyma gangrenosum |
| 730.00730.2 | Osteomyelitis |
| 630677 | Complications of pregnancy, childbirth and puerperium |
| 288.0 | Neutropenia |
| 684 | Impetigo |
| Procedure code | |
| 39.95 | Plasmapheresis |
| 99.71 | Hemoperfusion |
Classically, infections have been categorized as either community‐acquired (CAI) or nosocomial in origin. Until recently, this scheme was thought adequate to capture the differences in the microbiology and outcomes in the corresponding scenarios. However, recent evidence suggests that this distinction may no longer be valid. For example, with the spread and diffusion of healthcare delivery beyond the confines of the hospital along with the increasing use of broad spectrum antibiotics both in and out of the hospital, pathogens such as methicillin‐resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PA), traditionally thought to be confined to the hospital, are now seen in patients presenting from the community to the emergency department (ED).1, 2 Reflecting this shift in epidemiology, some national guidelines now recognize healthcare‐associated infection (HCAI) as a distinct entity.3 The concept of HCAI allows the clinician to identify patients who, despite suffering a community onset infection, still may be at risk for a resistant bacterial pathogen. Recent studies in both bloodstream infection and pneumonia have clearly demonstrated that those with HCAI have distinct microbiology and outcomes relative to those with pure CAI.47
Most work focusing on establishing HCAI has not addressed skin and soft tissue infections. These infections, although not often fatal, account for an increasing number of admissions to the hospital.8, 9 In addition, they may be associated with substantial morbidity and cost.8 Given that many pathogens such as S. aureus, which may be resistant to typical antimicrobials used in the ED, are also major culprits in complicated skin and skin structure infections (cSSSI), the HCAI paradigm may apply in cSSSI. Furthermore, because of these patterns of increased resistance, HCA‐cSSSI patients, similar to other HCAI groups, may be at an increased risk of being treated with initially inappropriate antibiotic therapy.7, 10
Since in the setting of other types of infection inappropriate empiric treatment has been shown to be associated with increased mortality and costs,7, 1015 and since indirect evidence suggests a similar impact on healthcare utilization among cSSSI patients,8 we hypothesized that among a cohort of patients hospitalized with a cSSSI, the initial empiric choice of therapy is independently associated with hospital length of stay (LOS). We performed a retrospective cohort study to address this question.
Methods
Study Design
We performed a single‐center retrospective cohort study of patients with cSSSI admitted to the hospital through the ED. All consecutive patients hospitalized between April 2006 and December 2007 meeting predefined inclusion criteria (see below) were enrolled. The study was approved by the Washington University School of Medicine Human Studies Committee, and informed consent was waived. We have previously reported on the characteristics and outcomes of this cohort, including both community‐acquired and HCA‐cSSSI patients.16
Study Cohort
All consecutive patients admitted from the community through the ED between April 2006 and December 2007 at the Barnes‐Jewish Hospital, a 1200‐bed university‐affiliated, urban teaching hospital in St. Louis, MO were included if: (1) they had a diagnosis of a predefined cSSSI (see Appendix Table A1, based on reference 8) and (2) they had a positive microbiology culture obtained within 24 hours of hospital admission. Similar to the work by Edelsberg et al.8 we excluded patients if certain diagnoses and procedures were present (Appendix Table A2). Cases were also excluded if they represented a readmission for the same diagnosis within 30 days of the original hospitalization.
Definitions
HCAI was defined as any cSSSI in a patient with a history of recent hospitalization (within the previous year, consistent with the previous study16), receiving antibiotics prior to admission (previous 90 days), transferring from a nursing home, or needing chronic dialysis. We defined a polymicrobial infection as one with more than one organism, and mixed infection as an infection with both a gram‐positive and a gram‐negative organism. Inappropriate empiric therapy took place if a patient did not receive treatment within 24 hours of the time the culture was obtained with an agent exhibiting in vitro activity against the isolated pathogen(s). In mixed infections, appropriate therapy was treatment within 24 hours of culture being obtained with agent(s) active against all pathogens recovered.
Data Elements
We collected information about multiple baseline demographic and clinical factors including: age, gender, race/ethnicity, comorbidities, the presence of risk factors for HCAI, the presence of bacteremia at admission, and the location of admission (ward vs. intensive care unit [ICU]). Bacteriology data included information on specific bacterium/a recovered from culture, the site of the culture (eg, tissue, blood), susceptibility patterns, and whether the infection was monomicrobial, polymicrobial, or mixed. When blood culture was available and positive, we prioritized this over wound and other cultures and designated the corresponding organism as the culprit in the index infection. Cultures growing our coagulase‐negative S. aureus were excluded as a probable contaminant. Treatment data included information on the choice of the antimicrobial therapy and the timing of its institution relative to the timing of obtaining the culture specimen. The presence of such procedures as incision and drainage (I&D) or debridement was recorded.
Statistical Analyses
Descriptive statistics comparing HCAI patients treated appropriately to those receiving inappropriate empiric coverage based on their clinical, demographic, microbiologic and treatment characteristics were computed. Hospital LOS served as the primary and hospital mortality as the secondary outcomes, comparing patients with HCAI treated appropriately to those treated inappropriately. All continuous variables were compared using Student's t test or the Mann‐Whitney U test as appropriate. All categorical variables were compared using the chi‐square test or Fisher's exact test. To assess the attributable impact of inappropriate therapy in HCAI on the outcomes of interest, general linear models with log transformation were developed to model hospital LOS parameters; all means are presented as geometric means. All potential risk factors significant at the 0.1 level in univariate analyses were entered into the model. All calculations were performed in Stata version 9 (Statacorp, College Station, TX).
Results
Of the 717 patients with culture‐positive cSSSI admitted during the study period, 527 (73.5%) were classified as HCAI. The most common reason for classification as an HCAI was recent hospitalization. Among those with an HCA‐cSSSI, 405 (76.9%) received appropriate empiric treatment, with nearly one‐quarter receiving inappropriate initial coverage. Those receiving inappropriate antibiotic were more likely to be African American, and had a higher likelihood of having end‐stage renal disease (ESRD) than those with appropriate coverage (Table 1). While those patients treated appropriately had higher rates of both cellulitis and abscess as the presenting infection, a substantially higher proportion of those receiving inappropriate initial treatment had a decubitus ulcer (29.5% vs. 10.9%, P <0.001), a device‐associated infection (42.6% vs. 28.6%, P = 0.004), and had evidence of bacteremia (68.9% vs. 57.8%, P = 0.028) than those receiving appropriate empiric coverage (Table 2).
| Inappropriate (n = 122), n (%) | Appropriate (n = 405), n (%) | P Value | |
|---|---|---|---|
| |||
| Age, years | 56.3 18.0 | 53.6 16.7 | 0.147 |
| Gender (F) | 62 (50.8) | 190 (46.9) | 0.449 |
| Race | |||
| Caucasian | 51 (41.8) | 219 (54.1) | 0.048 |
| African American | 68 (55.7) | 178 (43.9) | |
| Other | 3 (2.5) | 8 (2.0) | |
| HCAI risk factors | |||
| Recent hospitalization* | 110 (90.2) | 373 (92.1) | 0.498 |
| Within 90 days | 98 (80.3) | 274 (67.7) | 0.007 |
| >90 and 180 days | 52 (42.6) | 170 (42.0) | 0.899 |
| >180 days and 1 year | 46 (37.7) | 164 (40.5) | 0.581 |
| Prior antibiotics | 26 (21.3) | 90 (22.2) | 0.831 |
| Nursing home resident | 29 (23.8) | 54 (13.3) | 0.006 |
| Hemodialysis | 19 (15.6) | 39 (9.7) | 0.067 |
| Comorbidities | |||
| DM | 40 (37.8) | 128 (31.6) | 0.806 |
| PVD | 5 (4.1) | 15 (3.7) | 0.841 |
| Liver disease | 6 (4.9) | 33 (8.2) | 0.232 |
| Cancer | 21 (17.2) | 85 (21.0) | 0.362 |
| HIV | 1 (0.8) | 12 (3.0) | 0.316 |
| Organ transplant | 2 (1.6) | 8 (2.0) | 1.000 |
| Autoimmune disease | 5 (4.1) | 8 (2.0) | 0.185 |
| ESRD | 22 (18.0) | 46 (11.4) | 0.054 |
| Inappropriate (n = 122), n (%) | Appropriate (n = 405), n (%) | P Value | |
|---|---|---|---|
| |||
| Cellulitis | 28 (23.0) | 171 (42.2) | <0.001 |
| Decubitus ulcer | 36 (29.5) | 44 (10.9) | <0.001 |
| Post‐op wound | 25 (20.5) | 75 (18.5) | 0.626 |
| Device‐associated infection | 52 (42.6) | 116 (28.6) | 0.004 |
| Diabetic foot ulcer | 9 (7.4) | 24 (5.9) | 0.562 |
| Abscess | 22 (18.0) | 108 (26.7) | 0.052 |
| Other* | 2 (1.6) | 17 (4.2) | 0.269 |
| Presence of bacteremia | 84 (68.9) | 234 (57.8) | 0.028 |
The pathogens recovered from the appropriately and inappropriately treated groups are listed in Figure 1. While S. aureus overall was more common among those treated appropriately, the frequency of MRSA did not differ between the groups. Both E. faecalis and E. faecium were recovered more frequently in the inappropriate group, resulting in a similar pattern among the vancomycin‐resistant enterococcal species. Likewise, P. aeruginosa, P. mirabilis, and A. baumannii were all more frequently seen in the group treated inappropriately than in the group getting appropriate empiric coverage. A mixed infection was also more likely to be present among those not exposed (16.5%) than among those exposed (7.5%) to appropriate early therapy (P = 0.001) (Figure 1).
In terms of processes of care and outcomes (Table 3), commensurate with the higher prevalence of abscess in the appropriately treated group, the rate of I&D was significantly higher in this cohort (36.8%) than in the inappropriately treated (23.0%) group (P = 0.005). Need for initial ICU care did not differ as a function of appropriateness of therapy (P = 0.635).
| Inappropriate (n = 122) | Appropriate (n = 405) | P Value | |
|---|---|---|---|
| |||
| I&D/debridement | 28 (23.0%) | 149 (36.8%) | 0.005 |
| I&D in ED | 0 | 7 (1.7) | 0.361 |
| ICU | 9 (7.4%) | 25 (6.2%) | 0.635 |
| Hospital LOS, days | |||
| Median (IQR 25, 75) [Range] | 7.0 (4.2, 13.6) [0.686.6] | 6 (3.3, 10.1) [0.748.3] | 0.026 |
| Hospital mortality | 9 (7.4%) | 26 (6.4%) | 0.710 |
The unadjusted mortality rate was low overall and did not vary based on initial treatment (Table 3). In a generalized linear model with the log‐transformed LOS as the dependent variable, adjusting for multiple potential confounders, initial inappropriate antibiotic therapy had an attributable incremental increase in the hospital LOS of 1.8 days (95% CI, 1.42.3) (Table 4).
| Factor | Attributable LOS (days) | 95% CI | P Value |
|---|---|---|---|
| |||
| Infection type: device | 3.6 | 2.74.8 | <0.001 |
| Infection type: decubitus ulcer | 3.3 | 2.64.2 | <0.001 |
| Infection type: abscess | 2.5 | 1.64.0 | <0.001 |
| Organism: P. mirabilis | 2.2 | 1.43.4 | <0.001 |
| Organism: E. faecalis | 2.1 | 1.72.6 | <0.001 |
| Nursing home resident | 2.1 | 1.62.6 | <0.001 |
| Inappropriate antibiotic | 1.8 | 1.42.3 | <0.001 |
| Race: Non‐Caucasian | 0.31 | 0.240.41 | <0.001 |
| Organism: E. faecium | 0.23 | 0.150.35 | <0.001 |
Because bacteremia is known to be an effect modifier of the relationship between the empiric choice of antibiotic and infection outcomes, we further explored its role in the HCAI cSSSI on the outcomes of interest (Table 5). Similar to the effect detected in the overall cohort, treatment with inappropriate therapy was associated with an increase in the hospital LOS, but not hospital mortality in those with bacteremia, though this phenomenon was observed only among patients with secondary bacteremia, and not among those without (Table 5).
| Bacteremia Present (n = 318) | Bacteremia Absent (n = 209) | |||||
|---|---|---|---|---|---|---|
| I (n = 84) | A (n = 234) | P Value | I (n = 38) | A (n = 171) | P Value | |
| ||||||
| Hospital LOS, days | ||||||
| Mean SD | 14.4 27.5 | 9.8 9.7 | 0.041 | 6.6 6.8 | 6.9 8.2 | 0.761 |
| Median (IQR 25, 75) | 8.8 (5.4, 13.9) | 7.0 (4.3, 11.7) | 4.4 (2.4, 7.7) | 3.9 (2.0, 8.2) | ||
| Hospital mortality | 8 (9.5%) | 24 (10.3%) | 0.848 | 1 (2.6%) | 2 (1.2%) | 0.454 |
Discussion
This retrospective analysis provides evidence that inappropriate empiric antibiotic therapy for HCA‐cSSSI independently prolongs hospital LOS. The impact of inappropriate initial treatment on LOS is independent of many important confounders. In addition, we observed that this effect, while present among patients with secondary bacteremia, is absent among those without a blood stream infection.
To the best of our knowledge, ours is the first cohort study to examine the outcomes associated with inappropriate treatment of a HCAI cSSSI within the context of available microbiology data. Edelsberg et al.8 examined clinical and economic outcomes associated with the failure of the initial treatment of cSSSI. While not specifically focusing on HCAI patients, these authors noted an overall 23% initial therapy failure rate. Among those patients who failed initial therapy, the risk of hospital death was nearly 3‐fold higher (adjusted odds ratio [OR], 2.91; 95% CI, 2.343.62), and they incurred the mean of 5.4 additional hospital days, compared to patients treated successfully with the initial regimen.8 Our study confirms Edelsberg et al.'s8 observation of prolonged hospital LOS in association with treatment failure, and builds upon it by defining the actual LOS increment attributable to inappropriate empiric therapy. It is worth noting that the study by Edelsberg et al.,8 however, lacked explicit definition of the HCAI population and microbiology data, and used treatment failure as a surrogate marker for inappropriate treatment. It is likely these differences between our two studies in the underlying population and exposure definitions that account for the differences in the mortality data between that study and ours.
It is not fundamentally surprising that early exposure to inappropriate empiric therapy alters healthcare resource utilization outcomes for the worse. Others have demonstrated that infection with a resistant organism results in prolongation of hospital LOS and costs. For example, in a large cohort of over 600 surgical hospitalizations requiring treatment for a gram‐negative infection, antibiotic resistance was an independent predictor of increased LOS and costs.15 These authors quantified the incremental burden of early gram‐negative resistance at over $11,000 in hospital costs.15 Unfortunately, the treatment differences for resistant and sensitive organisms were not examined.15 Similarly, Shorr et al. examined risk factors for prolonged hospital LOS and increased costs in a cohort of 291 patients with MRSA sterile site infection.17 Because in this study 23% of the patients received inappropriate empiric therapy, the authors were able to examine the impact of this exposure on utilization outcomes.17 In an adjusted analysis, inappropriate initial treatment was associated with an incremental increase in the LOS of 2.5 days, corresponding to the unadjusted cost differential of nearly $6,000.17 Although focusing on a different population, our results are consistent with these previous observations that antibiotic resistance and early inappropriate therapy affect hospital utilization parameters, in our case by adding nearly 2 days to the hospital LOS.
Our study has a number of limitations. First, as a retrospective cohort study it is prone to various forms of bias, most notably selection bias. To minimize the possibility of such, we established a priori case definitions and enrolled consecutive patients over a specific period of time. Second, as in any observational study, confounding is an issue. We dealt with this statistically by constructing a multivariable regression model; however, the possibility of residual confounding remains. Third, because some of the wound and ulcer cultures likely were obtained with a swab and thus represented colonization, rather than infection, we may have over‐estimated the rate of inappropriate therapy, and this needs to be followed up in future prospective studies. Similarly, we may have over‐estimated the likelihood of inappropriate therapy among polymicrobial and mixed infections as well, given that, for example, a gram‐negative organism may carry a different clinical significance when cultured from blood (infection) than when it is detected in a decubitus ulcer (potential colonization). Fourth, because we limited our cohort to patients without deep‐seated infections, such as necrotizing fasciitis, other procedures were not collected. This omission may have led to either over‐estimation or under‐estimation of the impact of inappropriate therapy on the outcomes of interest.
The fact that our cohort represents a single large urban academic tertiary care medical center may limit the generalizability of our results only to centers that share similar characteristics. Finally, similar to most other studies of this type, ours lacks data on posthospitalization outcomes and for this reason limits itself to hospital outcomes only.
In summary, we have shown that, similar to other populations with HCAI, a substantial proportion (nearly 1/4) of cSSSI patients with HCAI receive inappropriate empiric therapy for their infection, and this early exposure, though not affecting hospital mortality, is associated with a significant prolongation of the hospitalization by as much as 2 days. Studies are needed to refine decision rules for risk‐stratifying patients with cSSSI HCAI in order to determine the probability of infection with a resistant organism. In turn, such instruments at the bedside may assure improved utilization of appropriately targeted empiric therapy that will both optimize individual patient outcomes and reduce the risk of emergence of antimicrobial resistance.
Appendix
| Principal diagnosis code | Description |
|---|---|
| 680 | Carbuncle and furuncle |
| 681 | Cellulitis and abscess of finger and toe |
| 682 | Other cellulitis and abscess |
| 683 | Acute lymphadenitis |
| 685 | Pilonidal cyst with abscess |
| 686 | Other local infections of skin and subcutaneous tissue |
| 707 | Decubitus ulcer |
| 707.1 | Ulcers of lower limbs, except decubitus |
| 707.8 | Chronic ulcer of other specified sites |
| 707.9 | Chronic ulcer of unspecified site |
| 958.3 | Posttraumatic wound infection, not elsewhere classified |
| 996.62 | Infection due to other vascular device, implant, and graft |
| 997.62 | Infection (chronic) of amputation stump |
| 998.5 | Postoperative wound infection |
| Diagnosis code | Description |
|---|---|
| 728.86 | Necrotizing fasciitis |
| 785.4 | Gangrene |
| 686.09 | Ecthyma gangrenosum |
| 730.00730.2 | Osteomyelitis |
| 630677 | Complications of pregnancy, childbirth and puerperium |
| 288.0 | Neutropenia |
| 684 | Impetigo |
| Procedure code | |
| 39.95 | Plasmapheresis |
| 99.71 | Hemoperfusion |
- ,,, et al.Invasive methicillin‐resistant Staphylococcus aureus infections in the United States.JAMA.2007;298:1762–1771.
- ,,, et al.Methicillin‐resistant S. aureus infections among patients in the emergency department.N Engl J Med.2006;17;355:666–674.
- Hospital‐Acquired Pneumonia Guideline Committee of the American Thoracic Society and Infectious Diseases Society of America.Guidelines for the management of adults with hospital‐acquired pneumonia, ventilator‐associated pneumonia, and healthcare‐associated pneumonia.Am J Respir Crit Care Med.2005;171:388–416.
- ,,, et al.Epidemiology and outcomes of health‐care‐associated pneumonia: Results from a large US database of culture‐positive pneumonia.Chest.2005;128:3854–3862.
- ,,, et al.Health care‐associated bloodstream infections in adults: A reason to change the accepted definition of community‐acquired infections.Ann Intern Med.2002;137:791–797.
- ,,,,,.Healthcare‐associated bloodstream infection: A distinct entity? Insights from a large U.S. database.Crit Care Med.2006;34:2588–2595.
- ,,, et al.Health care‐associated pneumonia and community‐acquired pneumonia: a single‐center experience.Antimicrob Agents Chemother.2007;51:3568–3573.
- ,,,,,.Clinical and economic consequences of failure of initial antibiotic therapy for hospitalized patients with complicated skin and skin‐structure infections.Infect Control Hosp Epidemiol.2008;29:160–169.
- ,,, et al.Skin, soft tissue, bone, and joint infections in hospitalized patients: Epidemiology and microbiological, clinical, and economic outcomes.Infect Control Hosp Epidemiol.2007;28:1290–1298.
- ,,, et al.Methicillin‐resistant Staphylococcus aureus sterile‐site infection: The importance of appropriate initial antimicrobial treatment.Crit Care Med.2006;34:2069–2074.
- ,,, et al.The influence of inadequate antimicrobial treatment of bloodstream infections on patient outcomes in the ICU setting.Chest.2000;118:146–155.
- ,.Modification of empiric antibiotic treatment in patients with pneumonia acquired in the intensive care unit.Intensive Care Med.1996;22:387–394.
- ,,, et al.Clinical importance of delays in the initiation of appropriate antibiotic treatment for ventilator‐associated pneumonia.Chest.2002;122:262–268.
- ,,,,.Antimicrobial therapy escalation and hospital mortality among patients with HCAP: A single center experience.Chest.2008;134:963–968.
- ,,, et al.Cost of gram‐negative resistance.Crit Care Med.2007;35:89–95.
- ,,, et al.Epidemiology and outcomes of hospitalizations with complicated skin and skin‐structure infections: implications of healthcare‐associated infection risk factors.Infect Control Hosp Epidemiol.2009;30:1203–1210.
- ,,.Inappropriate therapy for methicillin‐resistant Staphylococcus aureus: resource utilization and cost implications.Crit Care Med.2008;36:2335–2340.
- ,,, et al.Invasive methicillin‐resistant Staphylococcus aureus infections in the United States.JAMA.2007;298:1762–1771.
- ,,, et al.Methicillin‐resistant S. aureus infections among patients in the emergency department.N Engl J Med.2006;17;355:666–674.
- Hospital‐Acquired Pneumonia Guideline Committee of the American Thoracic Society and Infectious Diseases Society of America.Guidelines for the management of adults with hospital‐acquired pneumonia, ventilator‐associated pneumonia, and healthcare‐associated pneumonia.Am J Respir Crit Care Med.2005;171:388–416.
- ,,, et al.Epidemiology and outcomes of health‐care‐associated pneumonia: Results from a large US database of culture‐positive pneumonia.Chest.2005;128:3854–3862.
- ,,, et al.Health care‐associated bloodstream infections in adults: A reason to change the accepted definition of community‐acquired infections.Ann Intern Med.2002;137:791–797.
- ,,,,,.Healthcare‐associated bloodstream infection: A distinct entity? Insights from a large U.S. database.Crit Care Med.2006;34:2588–2595.
- ,,, et al.Health care‐associated pneumonia and community‐acquired pneumonia: a single‐center experience.Antimicrob Agents Chemother.2007;51:3568–3573.
- ,,,,,.Clinical and economic consequences of failure of initial antibiotic therapy for hospitalized patients with complicated skin and skin‐structure infections.Infect Control Hosp Epidemiol.2008;29:160–169.
- ,,, et al.Skin, soft tissue, bone, and joint infections in hospitalized patients: Epidemiology and microbiological, clinical, and economic outcomes.Infect Control Hosp Epidemiol.2007;28:1290–1298.
- ,,, et al.Methicillin‐resistant Staphylococcus aureus sterile‐site infection: The importance of appropriate initial antimicrobial treatment.Crit Care Med.2006;34:2069–2074.
- ,,, et al.The influence of inadequate antimicrobial treatment of bloodstream infections on patient outcomes in the ICU setting.Chest.2000;118:146–155.
- ,.Modification of empiric antibiotic treatment in patients with pneumonia acquired in the intensive care unit.Intensive Care Med.1996;22:387–394.
- ,,, et al.Clinical importance of delays in the initiation of appropriate antibiotic treatment for ventilator‐associated pneumonia.Chest.2002;122:262–268.
- ,,,,.Antimicrobial therapy escalation and hospital mortality among patients with HCAP: A single center experience.Chest.2008;134:963–968.
- ,,, et al.Cost of gram‐negative resistance.Crit Care Med.2007;35:89–95.
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