Herpes simplex virus (HSV) is a significant cause of pediatric hospitalization, morbidity and mortality, particularly in infants under 60 days of age, where HSV can present as meningoencephalitis, skin disease, or sepsis.14 Most prior studies use data from registries taken from single centers or a restricted group of hospitals. Thus, there is a paucity of recent, nationally‐representative information about the outcome of infants infected with HSV, especially those treated at nonteaching hospitals or with rarer comorbid conditions. The goal of this project was to determine the patient and hospital characteristics associated with worse clinical outcomes in infants under the age of 60 days admitted with HSV disease. We hypothesized that younger infants, infants with a concurrent congenital anomaly, and infants treated at non‐children's hospitals would have worse clinical outcomes. To answer these questions, we used 2003 panel data from the Healthcare Cost and Utilization Project (HCUP) Kids' Inpatient Database (KID), a nationally representative sample of inpatient hospitalizations in the United States.

Methods

Results

The 2003 KID identified 1587 hospitalizations for HSV in infants admitted at an age of 60 days or less in the entire United States. These infants had a total hospital cost of $27,147,000. Of the cohort, 10% had a concurrent congenital anomaly. Most infants (73.5%) were admitted within 14 days of birth, and 15.5% were transferred from another hospital. Based on APR‐DRG criteria, 33% of the infants were classified as having a moderate risk of death, 24% as major risk, and 12.2% as extreme risk. The majority of infants were treated at non‐children's hospitals (85.3%) in urban locations (91.5%). The average LOS was 12.0 0.6 days and the average total hospital cost was $17,382 1269. After admission, 267 of the infants, or 16.8%, had at least 1 serious complication. Fifty infants died during the hospitalization included in the KID.

Conclusions

There has been little prior information to guide practitioners and parents about factors that potentially influence clinical outcome of infants hospitalized with HSV in non‐children's hospitals, although over 80% of infants are managed at non‐children's hospitals. These studies also did not have the power to characterize the risk of poor clinical outcome associated with rarer clinical factors.1, 2, 6 This study, using nationally representative data, found that these rarer clinical factors and site of care may influence the outcomes of infants hospitalized with HSV, albeit in different methods. Younger age at admission and a coexisting congenital anomaly remained statistically significant predictors of worse clinical outcomes after controlling for various patient and hospital factors. Not all congenital anomalies increased the risk of death or serious complications; rather, anomalies that affected either the cardiopulmonary system or the central nervous system appeared to result in the highest increases in risk. This study also found that treatment of infants with HSV at a children's hospital was associated with a 28% shorter LOS after accounting for the sicker patients cared for by children's hospitals. This finding is in contrast to prior studies of common pediatric conditions, where there were no differences in the LOS between children's and non‐children's hospitals,17, 18 and severe sepsis, where children's hospitals had longer LOSs.19 These results confirm the importance of specific risk factors in predicting the likelihood that an infant admitted with HSV may have a poor clinical outcome. Also, these results emphasize the differences in outcomes that may occur at different types of hospitals.

This study is the first to find that certain congenital anomalies or conditions may be associated with worse clinical outcomes from HSV. There is little information in the literature to explain these findings. Those anomalies that affect the cardiopulmonary or central nervous system may either worsen the symptoms of HSV or predispose infants to have a serious complication, such as shock or respiratory failure. This finding would be similar to the increased risk of serious complications seen in infants with congenital heart disease who contract respiratory syncytial virus20 or infants with genetic syndromes who undergo heart surgery.21 Alternatively, because we do not have information on do‐not‐resuscitate status, the presence of one of these congenital anomalies may result in more withdrawal of care when an infant is infected with HSV and has a serious complication; the LOS of these children may not reflect these decisions because the decision to withdrawal care may only occur after the child's condition worsens significantly, which may happen any time during the disease course. However, this theory is less likely because we failed to find similar results with other congenital anomalies such as genetic or chromosomal syndromes. Further examination of these infants and their overall response to insults such as HSV is needed to understand how these anomalies influence the outcomes of a serious, unrelated illness.

Age upon admission was another important predictor of poor outcomes when analyzed in univariable or multivariable analysis. This result is consistent with prior work,14 which suggests that younger children are more likely to be hospitalized with either congenitally acquired HSV or systemic disease. The information contained in the KID does not allow us to determine whether young age is a risk factor for poor outcome irrespective of the clinical presentation of HSV, or whether age serves as a proxy for the appearance of more severe clinical disease. This effect of age remained present even after controlling for the higher risk of a serious complication and death in low birth weight infants. There are limited data that suggest that premature birth is an independent risk factor for worse outcomes associated with perinatal or congenital infection; 1 previous case study of Enterobacter sakazakii infections found a higher fatality rate for premature infants compared to term infants.22 This study supports these findings.

This study found that treatment at a children's hospital resulted in a 28% shorter LOS without a statistically significant difference in clinical outcomes after controlling for case‐mix differences. This finding is in contrast to prior studies of common pediatric conditions17, 18 and severe sepsis.19 There are several potential explanations for the difference in findings. For common pediatric conditions, there may be fewer variations in treatment style and less need for new diagnostic modalities that are more available at academic centers. For HSV disease, though, children's hospitals may also be more likely than non‐children's hospitals to perform polymerase‐chain reaction (PCR) testing for the diagnosis of perinatally acquired HSV, correctly identify the disorder, or receive the test results in a timely fashion. Pediatric subspecialists, such as infectious disease physicians or neurologists, are also likely to be more available at children's hospitals than at other centers. While the role of subspecialty consultation in improving outcomes for neonates with HSV is not known, improved outcomes at children's hospitals has been described for other serious conditions such as splenic injuries.23 Children's hospitals had higher daily costs than non‐children's hospitals, as has been found in other work.17, 19 Children's hospitals may be treating sicker patients, for whom we are unable to adequately adjust for their illness severity with hospital administrative data.17, 19 Also, there may be a greater use of medical tests and treatments that increase the costs of care. These costs do not include indirect costs to the families such as loss of work and travel costs. In light of the shorter LOS in children's hospitals, policy makers will need to balance the potentially higher daily costs of care with more efficient management of the disease process.

Because this study used hospital administrative records, there are a few limitations. We used ICD‐9CM diagnosis codes to identify patients, congenital anomalies, and complications. The diagnosis of some infants with HSV or less significant congenital anomalies could have been missed because clinicians either overlooked the disease or did not make the diagnosis before discharge. This form of spectrum bias would likely miss the infants with the least severe disease and make it more difficult to find the results that we found in this study.24 Prior work successfully used and validated similar ICD‐9CM codes to identify HSV cases among the different types of hospitals included in the KID.611 Our study design estimated 1587 cases of neonatal HSV in 2003. A prospective study of maternal serologic and virologic status during pregnancy estimated 480 to 2160 new cases of neonatal HSV per year.25 Thus, while miscoding is a potential limitation to our study, the overall numbers of patients in this study were similar to past annual estimates. One potential area of miscounting, though, was the inability of the KID to link the records of 16% of the identified infants with HSV whose care was transferred between hospitals. These infants may result in misleading LOS or cost information: lower for the transferring hospital, because they only kept the child a short period of time, or lower for the accepting hospital, as some of the total hospital stay is not accounted for in the KID. We accounted for this issue in 2 ways. First, we included a variable for being transferred in the multivariable models, and found no difference in any results when we omitted these patients from the analysis. Second, we performed a univariable analysis stratified by transfer status, which did not differ substantially from our main model for most variables. Accurate linkage of all the hospital records for an infant's hospital course, likely only through a mandatory reporting system for infant HSV, would help confirm the associations we identified in this study.

In conclusion, infants with congenital anomalies should be closely monitored for the development of serious complications associated with HSV, particularly those infants with congenital heart disease, pulmonary anomalies, or central nervous system anomalies. Closer investigation of the care practices that children's hospitals use in the management of infants with HSV is needed to improve the efficiency of care delivered to these infants, as HSV disease remains a significant public health problem.

Herpes simplex virus (HSV) is a significant cause of pediatric hospitalization, morbidity and mortality, particularly in infants under 60 days of age, where HSV can present as meningoencephalitis, skin disease, or sepsis.14 Most prior studies use data from registries taken from single centers or a restricted group of hospitals. Thus, there is a paucity of recent, nationally‐representative information about the outcome of infants infected with HSV, especially those treated at nonteaching hospitals or with rarer comorbid conditions. The goal of this project was to determine the patient and hospital characteristics associated with worse clinical outcomes in infants under the age of 60 days admitted with HSV disease. We hypothesized that younger infants, infants with a concurrent congenital anomaly, and infants treated at non‐children's hospitals would have worse clinical outcomes. To answer these questions, we used 2003 panel data from the Healthcare Cost and Utilization Project (HCUP) Kids' Inpatient Database (KID), a nationally representative sample of inpatient hospitalizations in the United States.

Methods

Results

The 2003 KID identified 1587 hospitalizations for HSV in infants admitted at an age of 60 days or less in the entire United States. These infants had a total hospital cost of $27,147,000. Of the cohort, 10% had a concurrent congenital anomaly. Most infants (73.5%) were admitted within 14 days of birth, and 15.5% were transferred from another hospital. Based on APR‐DRG criteria, 33% of the infants were classified as having a moderate risk of death, 24% as major risk, and 12.2% as extreme risk. The majority of infants were treated at non‐children's hospitals (85.3%) in urban locations (91.5%). The average LOS was 12.0 0.6 days and the average total hospital cost was $17,382 1269. After admission, 267 of the infants, or 16.8%, had at least 1 serious complication. Fifty infants died during the hospitalization included in the KID.

Conclusions

There has been little prior information to guide practitioners and parents about factors that potentially influence clinical outcome of infants hospitalized with HSV in non‐children's hospitals, although over 80% of infants are managed at non‐children's hospitals. These studies also did not have the power to characterize the risk of poor clinical outcome associated with rarer clinical factors.1, 2, 6 This study, using nationally representative data, found that these rarer clinical factors and site of care may influence the outcomes of infants hospitalized with HSV, albeit in different methods. Younger age at admission and a coexisting congenital anomaly remained statistically significant predictors of worse clinical outcomes after controlling for various patient and hospital factors. Not all congenital anomalies increased the risk of death or serious complications; rather, anomalies that affected either the cardiopulmonary system or the central nervous system appeared to result in the highest increases in risk. This study also found that treatment of infants with HSV at a children's hospital was associated with a 28% shorter LOS after accounting for the sicker patients cared for by children's hospitals. This finding is in contrast to prior studies of common pediatric conditions, where there were no differences in the LOS between children's and non‐children's hospitals,17, 18 and severe sepsis, where children's hospitals had longer LOSs.19 These results confirm the importance of specific risk factors in predicting the likelihood that an infant admitted with HSV may have a poor clinical outcome. Also, these results emphasize the differences in outcomes that may occur at different types of hospitals.

This study is the first to find that certain congenital anomalies or conditions may be associated with worse clinical outcomes from HSV. There is little information in the literature to explain these findings. Those anomalies that affect the cardiopulmonary or central nervous system may either worsen the symptoms of HSV or predispose infants to have a serious complication, such as shock or respiratory failure. This finding would be similar to the increased risk of serious complications seen in infants with congenital heart disease who contract respiratory syncytial virus20 or infants with genetic syndromes who undergo heart surgery.21 Alternatively, because we do not have information on do‐not‐resuscitate status, the presence of one of these congenital anomalies may result in more withdrawal of care when an infant is infected with HSV and has a serious complication; the LOS of these children may not reflect these decisions because the decision to withdrawal care may only occur after the child's condition worsens significantly, which may happen any time during the disease course. However, this theory is less likely because we failed to find similar results with other congenital anomalies such as genetic or chromosomal syndromes. Further examination of these infants and their overall response to insults such as HSV is needed to understand how these anomalies influence the outcomes of a serious, unrelated illness.

Age upon admission was another important predictor of poor outcomes when analyzed in univariable or multivariable analysis. This result is consistent with prior work,14 which suggests that younger children are more likely to be hospitalized with either congenitally acquired HSV or systemic disease. The information contained in the KID does not allow us to determine whether young age is a risk factor for poor outcome irrespective of the clinical presentation of HSV, or whether age serves as a proxy for the appearance of more severe clinical disease. This effect of age remained present even after controlling for the higher risk of a serious complication and death in low birth weight infants. There are limited data that suggest that premature birth is an independent risk factor for worse outcomes associated with perinatal or congenital infection; 1 previous case study of Enterobacter sakazakii infections found a higher fatality rate for premature infants compared to term infants.22 This study supports these findings.

This study found that treatment at a children's hospital resulted in a 28% shorter LOS without a statistically significant difference in clinical outcomes after controlling for case‐mix differences. This finding is in contrast to prior studies of common pediatric conditions17, 18 and severe sepsis.19 There are several potential explanations for the difference in findings. For common pediatric conditions, there may be fewer variations in treatment style and less need for new diagnostic modalities that are more available at academic centers. For HSV disease, though, children's hospitals may also be more likely than non‐children's hospitals to perform polymerase‐chain reaction (PCR) testing for the diagnosis of perinatally acquired HSV, correctly identify the disorder, or receive the test results in a timely fashion. Pediatric subspecialists, such as infectious disease physicians or neurologists, are also likely to be more available at children's hospitals than at other centers. While the role of subspecialty consultation in improving outcomes for neonates with HSV is not known, improved outcomes at children's hospitals has been described for other serious conditions such as splenic injuries.23 Children's hospitals had higher daily costs than non‐children's hospitals, as has been found in other work.17, 19 Children's hospitals may be treating sicker patients, for whom we are unable to adequately adjust for their illness severity with hospital administrative data.17, 19 Also, there may be a greater use of medical tests and treatments that increase the costs of care. These costs do not include indirect costs to the families such as loss of work and travel costs. In light of the shorter LOS in children's hospitals, policy makers will need to balance the potentially higher daily costs of care with more efficient management of the disease process.

Because this study used hospital administrative records, there are a few limitations. We used ICD‐9CM diagnosis codes to identify patients, congenital anomalies, and complications. The diagnosis of some infants with HSV or less significant congenital anomalies could have been missed because clinicians either overlooked the disease or did not make the diagnosis before discharge. This form of spectrum bias would likely miss the infants with the least severe disease and make it more difficult to find the results that we found in this study.24 Prior work successfully used and validated similar ICD‐9CM codes to identify HSV cases among the different types of hospitals included in the KID.611 Our study design estimated 1587 cases of neonatal HSV in 2003. A prospective study of maternal serologic and virologic status during pregnancy estimated 480 to 2160 new cases of neonatal HSV per year.25 Thus, while miscoding is a potential limitation to our study, the overall numbers of patients in this study were similar to past annual estimates. One potential area of miscounting, though, was the inability of the KID to link the records of 16% of the identified infants with HSV whose care was transferred between hospitals. These infants may result in misleading LOS or cost information: lower for the transferring hospital, because they only kept the child a short period of time, or lower for the accepting hospital, as some of the total hospital stay is not accounted for in the KID. We accounted for this issue in 2 ways. First, we included a variable for being transferred in the multivariable models, and found no difference in any results when we omitted these patients from the analysis. Second, we performed a univariable analysis stratified by transfer status, which did not differ substantially from our main model for most variables. Accurate linkage of all the hospital records for an infant's hospital course, likely only through a mandatory reporting system for infant HSV, would help confirm the associations we identified in this study.

In conclusion, infants with congenital anomalies should be closely monitored for the development of serious complications associated with HSV, particularly those infants with congenital heart disease, pulmonary anomalies, or central nervous system anomalies. Closer investigation of the care practices that children's hospitals use in the management of infants with HSV is needed to improve the efficiency of care delivered to these infants, as HSV disease remains a significant public health problem.

Herpes simplex virus (HSV) is a significant cause of pediatric hospitalization, morbidity and mortality, particularly in infants under 60 days of age, where HSV can present as meningoencephalitis, skin disease, or sepsis.14 Most prior studies use data from registries taken from single centers or a restricted group of hospitals. Thus, there is a paucity of recent, nationally‐representative information about the outcome of infants infected with HSV, especially those treated at nonteaching hospitals or with rarer comorbid conditions. The goal of this project was to determine the patient and hospital characteristics associated with worse clinical outcomes in infants under the age of 60 days admitted with HSV disease. We hypothesized that younger infants, infants with a concurrent congenital anomaly, and infants treated at non‐children's hospitals would have worse clinical outcomes. To answer these questions, we used 2003 panel data from the Healthcare Cost and Utilization Project (HCUP) Kids' Inpatient Database (KID), a nationally representative sample of inpatient hospitalizations in the United States.

Methods

Results

The 2003 KID identified 1587 hospitalizations for HSV in infants admitted at an age of 60 days or less in the entire United States. These infants had a total hospital cost of $27,147,000. Of the cohort, 10% had a concurrent congenital anomaly. Most infants (73.5%) were admitted within 14 days of birth, and 15.5% were transferred from another hospital. Based on APR‐DRG criteria, 33% of the infants were classified as having a moderate risk of death, 24% as major risk, and 12.2% as extreme risk. The majority of infants were treated at non‐children's hospitals (85.3%) in urban locations (91.5%). The average LOS was 12.0 0.6 days and the average total hospital cost was $17,382 1269. After admission, 267 of the infants, or 16.8%, had at least 1 serious complication. Fifty infants died during the hospitalization included in the KID.

Conclusions

There has been little prior information to guide practitioners and parents about factors that potentially influence clinical outcome of infants hospitalized with HSV in non‐children's hospitals, although over 80% of infants are managed at non‐children's hospitals. These studies also did not have the power to characterize the risk of poor clinical outcome associated with rarer clinical factors.1, 2, 6 This study, using nationally representative data, found that these rarer clinical factors and site of care may influence the outcomes of infants hospitalized with HSV, albeit in different methods. Younger age at admission and a coexisting congenital anomaly remained statistically significant predictors of worse clinical outcomes after controlling for various patient and hospital factors. Not all congenital anomalies increased the risk of death or serious complications; rather, anomalies that affected either the cardiopulmonary system or the central nervous system appeared to result in the highest increases in risk. This study also found that treatment of infants with HSV at a children's hospital was associated with a 28% shorter LOS after accounting for the sicker patients cared for by children's hospitals. This finding is in contrast to prior studies of common pediatric conditions, where there were no differences in the LOS between children's and non‐children's hospitals,17, 18 and severe sepsis, where children's hospitals had longer LOSs.19 These results confirm the importance of specific risk factors in predicting the likelihood that an infant admitted with HSV may have a poor clinical outcome. Also, these results emphasize the differences in outcomes that may occur at different types of hospitals.

This study is the first to find that certain congenital anomalies or conditions may be associated with worse clinical outcomes from HSV. There is little information in the literature to explain these findings. Those anomalies that affect the cardiopulmonary or central nervous system may either worsen the symptoms of HSV or predispose infants to have a serious complication, such as shock or respiratory failure. This finding would be similar to the increased risk of serious complications seen in infants with congenital heart disease who contract respiratory syncytial virus20 or infants with genetic syndromes who undergo heart surgery.21 Alternatively, because we do not have information on do‐not‐resuscitate status, the presence of one of these congenital anomalies may result in more withdrawal of care when an infant is infected with HSV and has a serious complication; the LOS of these children may not reflect these decisions because the decision to withdrawal care may only occur after the child's condition worsens significantly, which may happen any time during the disease course. However, this theory is less likely because we failed to find similar results with other congenital anomalies such as genetic or chromosomal syndromes. Further examination of these infants and their overall response to insults such as HSV is needed to understand how these anomalies influence the outcomes of a serious, unrelated illness.

Age upon admission was another important predictor of poor outcomes when analyzed in univariable or multivariable analysis. This result is consistent with prior work,14 which suggests that younger children are more likely to be hospitalized with either congenitally acquired HSV or systemic disease. The information contained in the KID does not allow us to determine whether young age is a risk factor for poor outcome irrespective of the clinical presentation of HSV, or whether age serves as a proxy for the appearance of more severe clinical disease. This effect of age remained present even after controlling for the higher risk of a serious complication and death in low birth weight infants. There are limited data that suggest that premature birth is an independent risk factor for worse outcomes associated with perinatal or congenital infection; 1 previous case study of Enterobacter sakazakii infections found a higher fatality rate for premature infants compared to term infants.22 This study supports these findings.

This study found that treatment at a children's hospital resulted in a 28% shorter LOS without a statistically significant difference in clinical outcomes after controlling for case‐mix differences. This finding is in contrast to prior studies of common pediatric conditions17, 18 and severe sepsis.19 There are several potential explanations for the difference in findings. For common pediatric conditions, there may be fewer variations in treatment style and less need for new diagnostic modalities that are more available at academic centers. For HSV disease, though, children's hospitals may also be more likely than non‐children's hospitals to perform polymerase‐chain reaction (PCR) testing for the diagnosis of perinatally acquired HSV, correctly identify the disorder, or receive the test results in a timely fashion. Pediatric subspecialists, such as infectious disease physicians or neurologists, are also likely to be more available at children's hospitals than at other centers. While the role of subspecialty consultation in improving outcomes for neonates with HSV is not known, improved outcomes at children's hospitals has been described for other serious conditions such as splenic injuries.23 Children's hospitals had higher daily costs than non‐children's hospitals, as has been found in other work.17, 19 Children's hospitals may be treating sicker patients, for whom we are unable to adequately adjust for their illness severity with hospital administrative data.17, 19 Also, there may be a greater use of medical tests and treatments that increase the costs of care. These costs do not include indirect costs to the families such as loss of work and travel costs. In light of the shorter LOS in children's hospitals, policy makers will need to balance the potentially higher daily costs of care with more efficient management of the disease process.

Because this study used hospital administrative records, there are a few limitations. We used ICD‐9CM diagnosis codes to identify patients, congenital anomalies, and complications. The diagnosis of some infants with HSV or less significant congenital anomalies could have been missed because clinicians either overlooked the disease or did not make the diagnosis before discharge. This form of spectrum bias would likely miss the infants with the least severe disease and make it more difficult to find the results that we found in this study.24 Prior work successfully used and validated similar ICD‐9CM codes to identify HSV cases among the different types of hospitals included in the KID.611 Our study design estimated 1587 cases of neonatal HSV in 2003. A prospective study of maternal serologic and virologic status during pregnancy estimated 480 to 2160 new cases of neonatal HSV per year.25 Thus, while miscoding is a potential limitation to our study, the overall numbers of patients in this study were similar to past annual estimates. One potential area of miscounting, though, was the inability of the KID to link the records of 16% of the identified infants with HSV whose care was transferred between hospitals. These infants may result in misleading LOS or cost information: lower for the transferring hospital, because they only kept the child a short period of time, or lower for the accepting hospital, as some of the total hospital stay is not accounted for in the KID. We accounted for this issue in 2 ways. First, we included a variable for being transferred in the multivariable models, and found no difference in any results when we omitted these patients from the analysis. Second, we performed a univariable analysis stratified by transfer status, which did not differ substantially from our main model for most variables. Accurate linkage of all the hospital records for an infant's hospital course, likely only through a mandatory reporting system for infant HSV, would help confirm the associations we identified in this study.

In conclusion, infants with congenital anomalies should be closely monitored for the development of serious complications associated with HSV, particularly those infants with congenital heart disease, pulmonary anomalies, or central nervous system anomalies. Closer investigation of the care practices that children's hospitals use in the management of infants with HSV is needed to improve the efficiency of care delivered to these infants, as HSV disease remains a significant public health problem.

A previously healthy 66‐year‐old man was admitted with a 4‐day history of high fever and an extensive, nonpruritic, nonmigratory, erythematous rash with areas of induration over his torso (Figure 1A). Biopsy of the rash, which spontaneously subsided within 8 days, revealed only nonspecific superficial and deep perivascular lymphocytic infiltration, without vasculitis, granulomas, or immunohistochemical evidence of malignant cells (Figure 1B). Blood cultures grew spiral‐shaped Gram‐negative rods (Figure 1C), which were identified as Helicobacter cinaedi by polymerase chain reaction (PCR). H. cinaedi is a rare pathogen that is reported to cause bacteremia in immunocompromised hosts. Peripheral blood showed more than 2000/L of lymphocytes with prominent hyperlobulated flower‐like nuclei (Figure 1D), which were CD4+/CD8 and CD25+ by flow cytometry. Human T‐lymphotropic virus 1 (HTLV‐1) antibody was positive, highlighting the fact that the patient's mother was from southern Kyushu, Japan, where HTLV‐1 is endemic. Diagnosis of adult T‐cell leukemia was confirmed by southern blot hybridization analysis. We believe that this case makes an important addition to the library of annular or gyrate erythemas, which can be secondary to bacteremia, leukemia, or both.

Figure 1

A previously healthy 66‐year‐old man was admitted with a 4‐day history of high fever and an extensive, nonpruritic, nonmigratory, erythematous rash with areas of induration over his torso (Figure 1A). Biopsy of the rash, which spontaneously subsided within 8 days, revealed only nonspecific superficial and deep perivascular lymphocytic infiltration, without vasculitis, granulomas, or immunohistochemical evidence of malignant cells (Figure 1B). Blood cultures grew spiral‐shaped Gram‐negative rods (Figure 1C), which were identified as Helicobacter cinaedi by polymerase chain reaction (PCR). H. cinaedi is a rare pathogen that is reported to cause bacteremia in immunocompromised hosts. Peripheral blood showed more than 2000/L of lymphocytes with prominent hyperlobulated flower‐like nuclei (Figure 1D), which were CD4+/CD8 and CD25+ by flow cytometry. Human T‐lymphotropic virus 1 (HTLV‐1) antibody was positive, highlighting the fact that the patient's mother was from southern Kyushu, Japan, where HTLV‐1 is endemic. Diagnosis of adult T‐cell leukemia was confirmed by southern blot hybridization analysis. We believe that this case makes an important addition to the library of annular or gyrate erythemas, which can be secondary to bacteremia, leukemia, or both.

Figure 1

A previously healthy 66‐year‐old man was admitted with a 4‐day history of high fever and an extensive, nonpruritic, nonmigratory, erythematous rash with areas of induration over his torso (Figure 1A). Biopsy of the rash, which spontaneously subsided within 8 days, revealed only nonspecific superficial and deep perivascular lymphocytic infiltration, without vasculitis, granulomas, or immunohistochemical evidence of malignant cells (Figure 1B). Blood cultures grew spiral‐shaped Gram‐negative rods (Figure 1C), which were identified as Helicobacter cinaedi by polymerase chain reaction (PCR). H. cinaedi is a rare pathogen that is reported to cause bacteremia in immunocompromised hosts. Peripheral blood showed more than 2000/L of lymphocytes with prominent hyperlobulated flower‐like nuclei (Figure 1D), which were CD4+/CD8 and CD25+ by flow cytometry. Human T‐lymphotropic virus 1 (HTLV‐1) antibody was positive, highlighting the fact that the patient's mother was from southern Kyushu, Japan, where HTLV‐1 is endemic. Diagnosis of adult T‐cell leukemia was confirmed by southern blot hybridization analysis. We believe that this case makes an important addition to the library of annular or gyrate erythemas, which can be secondary to bacteremia, leukemia, or both.

Figure 1

Pneumonia is the second most common infection in nursing home residents after urinary tract infection, and is the most common reason for transfer to the hospital.1 Although it remains difficult to determine the incidence of pneumonia in institutionalized elderly patients, an estimated 4 million cases of nursing homeacquired pneumonia (NHAP) occur annually in the United States and result in more than 600,000 emergency department visits.2 In the past 2 decades, multiple studies have documented the rapid rise in drug resistance among common pathogens responsible for pneumonia in the elderly and the acquisition of multidrug‐resistant organisms in residents of long‐term care facilities.3, 4 Health care practitioners are faced with the dilemma of attempting to limit broad‐spectrum antimicrobial drug use while striving to maximize therapeutic efficacy in individual patients.5 The current practice guidelines for the management of NHAP from various professional societies provide mixed messages on the class of antibiotics for patients requiring hospitalization.2, 68 While the 2000 Canadian and the 2003 Infectious Disease Society of America (IDSA) guidelines advocate a community‐acquired pneumonia‐like approach to therapy, the 2005 American Thoracic Society (ATS)/IDSA guidelines and the 2007 IDSA/ATS guidelines consider drug‐resistant pathogens (DRPs) (ie, methicillin‐resistant Staphylococcus aureus [MRSA] and Pseudomonas aeruginosa) to be major etiologic agents in NHAP and thus the empiric treatment recommendations focus specifically on these pathogens (Table 1).

Given these differences in antibiotic recommendations among the various guidelines, we sought to examine the antimicrobial prescription patterns in hospitalized non‐critically‐ill patients with NHAP in multiple tertiary care facilities vis‐‐vis the population demographics and clinical characteristics.

Methods

Results

A total of 397 subjects with NHAP were included in the study. The mean age of the cohort group was 76.8 13.5 years. Eighty percent had 2 or more chronic diseases. Degenerative nervous system, cardiac, and pulmonary diseases accounted for the majority of underlying comorbidities. Demographic and clinical characteristics of the study population are presented in Table 2. At the time of admission, 17% of patients had received antimicrobial therapy for a respiratory ailment within the last week prior to transfer to an acute care facility. The most commonly prescribed agents at the nursing home were an oral fluoroquinolone (81%), a cephalosporin (14%), or a macrolide (3%).

Of the 397 patients who met the criteria for NHAP, all but 5 patients received antimicrobial therapy. The 3 most commonly used antimicrobial compounds for inpatient treatment were fluoroquinolones (51.4%), ceftriaxone (45.0%), and azithromycin (42.1%). None of the participating hospitals had an antibiotic restriction policy for the use of fluoroquinolones or vancomycin.

Monotherapy was prescribed in 57.4%. Fluoroquinolones represented 79.5% of these cases. The other monotherapy choices included a third‐generation cephalosporin (10.7%), piperacillin/tazobactam (8%), and vancomycin (0.2%). Combination therapy consisted mainly of a macrolide plus a third‐generation cephalosporin (74/168; 44%). Other combination regimens included vancomycin plus piperacillin/tazobactam plus ciprofloxacin (35%), vancomycin plus imipenem plus ciprofloxacin (9%), vancomycin plus piperacillin/tazobactam plus azithromycin (4%), vancomycin plus piperacillin/tazobactam (7%), and piperacillin/tazobactam plus azithromycin (1%). Figure 1 shows the distribution of vancomycin and fluoroquinolones use across the different age groups. While the use of fluoroquinolones (P = 0.76) was comparable between groups, there was a significant trend in prescribing less vancomycin with increasing age (P < 0.001). As for the rest of the antibiotics, there was no difference in the overall use of macrolides (P = 0.53), cephalosporins (P = 0.84), or carbapenems (P = 0.67) among age groups. Clindamycin was only used in 9 (2%) out of 392 patients. None of the patients had an aminoglycoside or a sulfa drug prescribed. We also found no difference in terms of antibiotic choice or use of combination therapy among the 3 hospitals (P = 0.78, and P = 0.52; respectively).

Figure 1

Antibiotic choices were influenced by severity of illness. There was an inverse relationship between PSI classes and the use of either fluoroquinolones or ceftriaxone plus azithromycin (P = 0.02) (Figure 2). Patients with higher acuity of illness were more likely to receive combination regimens that include vancomycin plus piperacillin/tazobactam than those with lower acuity of illness (P < 0.001). Neither the comorbidity index nor the ADL scores had a significant impact on the use of combination therapy (P = 0.49 and P = 0.2; respectively). There was a trend toward association between increasing ADL score and the use of vancomycin plus piperacillin/tazobactam but it did not reach statistical significance (P = 0.06). Of interest, patients who were admitted on the University‐affiliated service were more likely to receive combination therapy than those who were under the care of private service (P < 0.001) (Figure 3). Ceftriaxone plus azithromycin accounted for the majority of combination regimens irrespective of physicians' affiliation.

Figure 2

Figure 3

Overall, there were more patients who received antibiotic therapy in compliance with the 2003 IDSA guidelines6 compared with the 2005 ATS/IDSA guidelines7 (65% vs. 19%, respectively; P < 0.001). A positive correlation was noted between severity of illness and adherence to the 2005 ATS/IDSA antimicrobial recommendations (P = 0.02). However, neither the burden of comorbidities nor the functional status was associated with the use of guidelines (P = 0.76 and P = 0.43; respectively).

Duration of therapy ranged from 3 to 21 days with a median of 8 days. The choice of antibiotics, burden of comorbidities, DNR status, or PSI scores had no correlation with antibiotic duration. Only the presence of bacteremia was associated with more than 8 days of antibiotic duration (P < 0.001) (Figure 4). On average, bacteremic patients received 10.1 3.3 (range, 6‐21) days of antimicrobial therapy compared to 7.8 4.1 (range, 319) days for nonbacteremic cases (P < 0.001). During the course of hospitalization, change in antibiotics occurred in 35 (9%) out of the 392 patients, with the majority of substitutions affecting those who were initially prescribed a regimen that included vancomycin plus piperacillin/tazobactam. In these cases, patients were most commonly switched to fluoroquinolones (n = 20), followed by cephalosporins (n = 11).

Figure 4

Discussion

Our study suggests that antimicrobial selection among hospitalized nursing homes patients with pneumonia is influenced by patients' age, severity of illness, and provider's academic affiliation.

This is the first comprehensive study, to our knowledge, to report on the type, distribution, and pattern of antimicrobials prescribed among institutionalized patients requiring hospital admission. Various treatment regimens have been investigated in the last 2 decades using both retrospective and prospective randomized clinical trials to examine the efficacy and safety of parenteral and oral antibiotics in nursing homes.1316 However, there are no randomized controlled clinical trials for the treatment of hospitalized NHAP on which to base treatment recommendations. For some healthcare providers, the treatment parallels the coverage of patients with community‐acquired pneumonia; for others, broad‐spectrum coverage is the norm. In the absence of validated guidelines, the present investigation shows that prescription patterns varied across demographic and clinical characteristics. Fluoroquinolones were the preferred agents for the initial therapy of NHAP across all age groups, probably because of their single daily dosing, broad spectrum coverage against typical and atypical pathogens, and favorable side effect profile. Conversely, the use of vancomycin tended to decline in older age groups. This decline could be attributed to the need for frequent monitoring of trough levels when venous access can be difficult, lack of oral formulation, or potential toxicity. Further studies are needed to examine the validity of this pattern.

To our knowledge, compliance with guidelines regarding treatment of NHAP has not been previously reported. Despite recent studies suggesting that adherence to community‐acquired pneumonia guidelines resulted in reduced need for hospitalization, shorter stays, and lower mortality,1721 our findings indicated a rather low compliance with the most recently published guidelines. Potential reasons for the low levels of compliance include lack of awareness, time lag for the information to be disseminated in the medical community, lack of endorsement by local opinion leaders, or local barriers to implementation of these guidelines. Unfortunately, little is known about physicians' familiarity and attitude toward NHAP guidelines use. Efforts to improve the effectiveness of pneumonia care will depend on future studies aiming at identifying factors that influence nonadherence.

Severity of illness had a significant influence on the prescription pattern of antimicrobial therapy. As the PSI increased, treatment with a fluoroquinolone or with combination therapy of nonpseudomonal third‐generation cephalosporin plus macrolide was replaced by a broader spectrum of antimicrobial coverage. We believe that healthcare providers' prescriptions may be influenced by the recommendations of the ATS guidelines for the treatment of health care associated pneumonia,7 in which antimicrobial therapy for severely ill patients admitted from long‐term care facilities is directed toward multidrug resistant pathogens. The validity of this practice, however, remains the subject of intense debate,2225 driven by the absence of randomized trials showing improved morbidity and mortality.

Few formal clinical trials exist to guide the length of therapy of hospitalized patients with NHAP. The usual recommendation ranges from 7 to 14 days.16, 26 The median duration of 8 days observed in the current study is consistent with length of therapy advocated in the literature.16 Yet, prolonging antibiotic duration has been suggested when clinical severity of illness is high, comorbid illnesses are multiple, and expected resolution is delayed.27 Arguing against such a practice is evidence from meta‐analysis,28 expert reviews,29 and clinical investigation.30 Prescribing principles are nevertheless unlikely to induce substantial change unless their dissemination and promotion is sustained through intensive continuing educational programs for physicians and pharmacists.3133

Our study has a number of limitations. First, the cohort group described in this investigation consists of institutionalized patients in Western New York and hence the antibiotic prescribing patterns may vary in other locations. Second, we did not have adequate microbial information to fully assess the appropriateness of antimicrobial therapy. Third, the absence of microbial etiology may have resulted in incorrect identification of patients with pneumonia. Further, retrospective data extraction is notoriously imperfect, and pneumonia cases may have been missed because of either coding errors or atypical manifestations. However, we have used strict inclusion criteria in to minimize any potential bias. Fourth, the results of this study describe patterns of antibiotic utilization in the treatment of NHAP but do not provide reasoning for such a practice. The rationale behind these practices can only be discerned by a survey of healthcare providers.

In conclusion, we have observed in this study a poor compliance with the current guidelines for the treatment of NHAP. It is generally accepted that physicians' prescribing habits are influenced by their understanding of the pathophysiology and epidemiology of the infection being treated, as well as the pharmacology and spectrum of available antimicrobials. In the absence of outcome data, translation of this knowledge into practice may be influenced by a number of factors, such as the physician's preference, the academic milieu in which the practice occurs, and more importantly, by the patients' clinical condition.

Pneumonia is the second most common infection in nursing home residents after urinary tract infection, and is the most common reason for transfer to the hospital.1 Although it remains difficult to determine the incidence of pneumonia in institutionalized elderly patients, an estimated 4 million cases of nursing homeacquired pneumonia (NHAP) occur annually in the United States and result in more than 600,000 emergency department visits.2 In the past 2 decades, multiple studies have documented the rapid rise in drug resistance among common pathogens responsible for pneumonia in the elderly and the acquisition of multidrug‐resistant organisms in residents of long‐term care facilities.3, 4 Health care practitioners are faced with the dilemma of attempting to limit broad‐spectrum antimicrobial drug use while striving to maximize therapeutic efficacy in individual patients.5 The current practice guidelines for the management of NHAP from various professional societies provide mixed messages on the class of antibiotics for patients requiring hospitalization.2, 68 While the 2000 Canadian and the 2003 Infectious Disease Society of America (IDSA) guidelines advocate a community‐acquired pneumonia‐like approach to therapy, the 2005 American Thoracic Society (ATS)/IDSA guidelines and the 2007 IDSA/ATS guidelines consider drug‐resistant pathogens (DRPs) (ie, methicillin‐resistant Staphylococcus aureus [MRSA] and Pseudomonas aeruginosa) to be major etiologic agents in NHAP and thus the empiric treatment recommendations focus specifically on these pathogens (Table 1).

Given these differences in antibiotic recommendations among the various guidelines, we sought to examine the antimicrobial prescription patterns in hospitalized non‐critically‐ill patients with NHAP in multiple tertiary care facilities vis‐‐vis the population demographics and clinical characteristics.

Methods

Results

A total of 397 subjects with NHAP were included in the study. The mean age of the cohort group was 76.8 13.5 years. Eighty percent had 2 or more chronic diseases. Degenerative nervous system, cardiac, and pulmonary diseases accounted for the majority of underlying comorbidities. Demographic and clinical characteristics of the study population are presented in Table 2. At the time of admission, 17% of patients had received antimicrobial therapy for a respiratory ailment within the last week prior to transfer to an acute care facility. The most commonly prescribed agents at the nursing home were an oral fluoroquinolone (81%), a cephalosporin (14%), or a macrolide (3%).

Of the 397 patients who met the criteria for NHAP, all but 5 patients received antimicrobial therapy. The 3 most commonly used antimicrobial compounds for inpatient treatment were fluoroquinolones (51.4%), ceftriaxone (45.0%), and azithromycin (42.1%). None of the participating hospitals had an antibiotic restriction policy for the use of fluoroquinolones or vancomycin.

Monotherapy was prescribed in 57.4%. Fluoroquinolones represented 79.5% of these cases. The other monotherapy choices included a third‐generation cephalosporin (10.7%), piperacillin/tazobactam (8%), and vancomycin (0.2%). Combination therapy consisted mainly of a macrolide plus a third‐generation cephalosporin (74/168; 44%). Other combination regimens included vancomycin plus piperacillin/tazobactam plus ciprofloxacin (35%), vancomycin plus imipenem plus ciprofloxacin (9%), vancomycin plus piperacillin/tazobactam plus azithromycin (4%), vancomycin plus piperacillin/tazobactam (7%), and piperacillin/tazobactam plus azithromycin (1%). Figure 1 shows the distribution of vancomycin and fluoroquinolones use across the different age groups. While the use of fluoroquinolones (P = 0.76) was comparable between groups, there was a significant trend in prescribing less vancomycin with increasing age (P < 0.001). As for the rest of the antibiotics, there was no difference in the overall use of macrolides (P = 0.53), cephalosporins (P = 0.84), or carbapenems (P = 0.67) among age groups. Clindamycin was only used in 9 (2%) out of 392 patients. None of the patients had an aminoglycoside or a sulfa drug prescribed. We also found no difference in terms of antibiotic choice or use of combination therapy among the 3 hospitals (P = 0.78, and P = 0.52; respectively).

Figure 1

Antibiotic choices were influenced by severity of illness. There was an inverse relationship between PSI classes and the use of either fluoroquinolones or ceftriaxone plus azithromycin (P = 0.02) (Figure 2). Patients with higher acuity of illness were more likely to receive combination regimens that include vancomycin plus piperacillin/tazobactam than those with lower acuity of illness (P < 0.001). Neither the comorbidity index nor the ADL scores had a significant impact on the use of combination therapy (P = 0.49 and P = 0.2; respectively). There was a trend toward association between increasing ADL score and the use of vancomycin plus piperacillin/tazobactam but it did not reach statistical significance (P = 0.06). Of interest, patients who were admitted on the University‐affiliated service were more likely to receive combination therapy than those who were under the care of private service (P < 0.001) (Figure 3). Ceftriaxone plus azithromycin accounted for the majority of combination regimens irrespective of physicians' affiliation.

Figure 2

Figure 3

Overall, there were more patients who received antibiotic therapy in compliance with the 2003 IDSA guidelines6 compared with the 2005 ATS/IDSA guidelines7 (65% vs. 19%, respectively; P < 0.001). A positive correlation was noted between severity of illness and adherence to the 2005 ATS/IDSA antimicrobial recommendations (P = 0.02). However, neither the burden of comorbidities nor the functional status was associated with the use of guidelines (P = 0.76 and P = 0.43; respectively).

Duration of therapy ranged from 3 to 21 days with a median of 8 days. The choice of antibiotics, burden of comorbidities, DNR status, or PSI scores had no correlation with antibiotic duration. Only the presence of bacteremia was associated with more than 8 days of antibiotic duration (P < 0.001) (Figure 4). On average, bacteremic patients received 10.1 3.3 (range, 6‐21) days of antimicrobial therapy compared to 7.8 4.1 (range, 319) days for nonbacteremic cases (P < 0.001). During the course of hospitalization, change in antibiotics occurred in 35 (9%) out of the 392 patients, with the majority of substitutions affecting those who were initially prescribed a regimen that included vancomycin plus piperacillin/tazobactam. In these cases, patients were most commonly switched to fluoroquinolones (n = 20), followed by cephalosporins (n = 11).

Figure 4

Discussion

Our study suggests that antimicrobial selection among hospitalized nursing homes patients with pneumonia is influenced by patients' age, severity of illness, and provider's academic affiliation.

This is the first comprehensive study, to our knowledge, to report on the type, distribution, and pattern of antimicrobials prescribed among institutionalized patients requiring hospital admission. Various treatment regimens have been investigated in the last 2 decades using both retrospective and prospective randomized clinical trials to examine the efficacy and safety of parenteral and oral antibiotics in nursing homes.1316 However, there are no randomized controlled clinical trials for the treatment of hospitalized NHAP on which to base treatment recommendations. For some healthcare providers, the treatment parallels the coverage of patients with community‐acquired pneumonia; for others, broad‐spectrum coverage is the norm. In the absence of validated guidelines, the present investigation shows that prescription patterns varied across demographic and clinical characteristics. Fluoroquinolones were the preferred agents for the initial therapy of NHAP across all age groups, probably because of their single daily dosing, broad spectrum coverage against typical and atypical pathogens, and favorable side effect profile. Conversely, the use of vancomycin tended to decline in older age groups. This decline could be attributed to the need for frequent monitoring of trough levels when venous access can be difficult, lack of oral formulation, or potential toxicity. Further studies are needed to examine the validity of this pattern.

To our knowledge, compliance with guidelines regarding treatment of NHAP has not been previously reported. Despite recent studies suggesting that adherence to community‐acquired pneumonia guidelines resulted in reduced need for hospitalization, shorter stays, and lower mortality,1721 our findings indicated a rather low compliance with the most recently published guidelines. Potential reasons for the low levels of compliance include lack of awareness, time lag for the information to be disseminated in the medical community, lack of endorsement by local opinion leaders, or local barriers to implementation of these guidelines. Unfortunately, little is known about physicians' familiarity and attitude toward NHAP guidelines use. Efforts to improve the effectiveness of pneumonia care will depend on future studies aiming at identifying factors that influence nonadherence.

Severity of illness had a significant influence on the prescription pattern of antimicrobial therapy. As the PSI increased, treatment with a fluoroquinolone or with combination therapy of nonpseudomonal third‐generation cephalosporin plus macrolide was replaced by a broader spectrum of antimicrobial coverage. We believe that healthcare providers' prescriptions may be influenced by the recommendations of the ATS guidelines for the treatment of health care associated pneumonia,7 in which antimicrobial therapy for severely ill patients admitted from long‐term care facilities is directed toward multidrug resistant pathogens. The validity of this practice, however, remains the subject of intense debate,2225 driven by the absence of randomized trials showing improved morbidity and mortality.

Few formal clinical trials exist to guide the length of therapy of hospitalized patients with NHAP. The usual recommendation ranges from 7 to 14 days.16, 26 The median duration of 8 days observed in the current study is consistent with length of therapy advocated in the literature.16 Yet, prolonging antibiotic duration has been suggested when clinical severity of illness is high, comorbid illnesses are multiple, and expected resolution is delayed.27 Arguing against such a practice is evidence from meta‐analysis,28 expert reviews,29 and clinical investigation.30 Prescribing principles are nevertheless unlikely to induce substantial change unless their dissemination and promotion is sustained through intensive continuing educational programs for physicians and pharmacists.3133

Our study has a number of limitations. First, the cohort group described in this investigation consists of institutionalized patients in Western New York and hence the antibiotic prescribing patterns may vary in other locations. Second, we did not have adequate microbial information to fully assess the appropriateness of antimicrobial therapy. Third, the absence of microbial etiology may have resulted in incorrect identification of patients with pneumonia. Further, retrospective data extraction is notoriously imperfect, and pneumonia cases may have been missed because of either coding errors or atypical manifestations. However, we have used strict inclusion criteria in to minimize any potential bias. Fourth, the results of this study describe patterns of antibiotic utilization in the treatment of NHAP but do not provide reasoning for such a practice. The rationale behind these practices can only be discerned by a survey of healthcare providers.

In conclusion, we have observed in this study a poor compliance with the current guidelines for the treatment of NHAP. It is generally accepted that physicians' prescribing habits are influenced by their understanding of the pathophysiology and epidemiology of the infection being treated, as well as the pharmacology and spectrum of available antimicrobials. In the absence of outcome data, translation of this knowledge into practice may be influenced by a number of factors, such as the physician's preference, the academic milieu in which the practice occurs, and more importantly, by the patients' clinical condition.

Pneumonia is the second most common infection in nursing home residents after urinary tract infection, and is the most common reason for transfer to the hospital.1 Although it remains difficult to determine the incidence of pneumonia in institutionalized elderly patients, an estimated 4 million cases of nursing homeacquired pneumonia (NHAP) occur annually in the United States and result in more than 600,000 emergency department visits.2 In the past 2 decades, multiple studies have documented the rapid rise in drug resistance among common pathogens responsible for pneumonia in the elderly and the acquisition of multidrug‐resistant organisms in residents of long‐term care facilities.3, 4 Health care practitioners are faced with the dilemma of attempting to limit broad‐spectrum antimicrobial drug use while striving to maximize therapeutic efficacy in individual patients.5 The current practice guidelines for the management of NHAP from various professional societies provide mixed messages on the class of antibiotics for patients requiring hospitalization.2, 68 While the 2000 Canadian and the 2003 Infectious Disease Society of America (IDSA) guidelines advocate a community‐acquired pneumonia‐like approach to therapy, the 2005 American Thoracic Society (ATS)/IDSA guidelines and the 2007 IDSA/ATS guidelines consider drug‐resistant pathogens (DRPs) (ie, methicillin‐resistant Staphylococcus aureus [MRSA] and Pseudomonas aeruginosa) to be major etiologic agents in NHAP and thus the empiric treatment recommendations focus specifically on these pathogens (Table 1).

Given these differences in antibiotic recommendations among the various guidelines, we sought to examine the antimicrobial prescription patterns in hospitalized non‐critically‐ill patients with NHAP in multiple tertiary care facilities vis‐‐vis the population demographics and clinical characteristics.

Methods

Results

A total of 397 subjects with NHAP were included in the study. The mean age of the cohort group was 76.8 13.5 years. Eighty percent had 2 or more chronic diseases. Degenerative nervous system, cardiac, and pulmonary diseases accounted for the majority of underlying comorbidities. Demographic and clinical characteristics of the study population are presented in Table 2. At the time of admission, 17% of patients had received antimicrobial therapy for a respiratory ailment within the last week prior to transfer to an acute care facility. The most commonly prescribed agents at the nursing home were an oral fluoroquinolone (81%), a cephalosporin (14%), or a macrolide (3%).

Of the 397 patients who met the criteria for NHAP, all but 5 patients received antimicrobial therapy. The 3 most commonly used antimicrobial compounds for inpatient treatment were fluoroquinolones (51.4%), ceftriaxone (45.0%), and azithromycin (42.1%). None of the participating hospitals had an antibiotic restriction policy for the use of fluoroquinolones or vancomycin.

Monotherapy was prescribed in 57.4%. Fluoroquinolones represented 79.5% of these cases. The other monotherapy choices included a third‐generation cephalosporin (10.7%), piperacillin/tazobactam (8%), and vancomycin (0.2%). Combination therapy consisted mainly of a macrolide plus a third‐generation cephalosporin (74/168; 44%). Other combination regimens included vancomycin plus piperacillin/tazobactam plus ciprofloxacin (35%), vancomycin plus imipenem plus ciprofloxacin (9%), vancomycin plus piperacillin/tazobactam plus azithromycin (4%), vancomycin plus piperacillin/tazobactam (7%), and piperacillin/tazobactam plus azithromycin (1%). Figure 1 shows the distribution of vancomycin and fluoroquinolones use across the different age groups. While the use of fluoroquinolones (P = 0.76) was comparable between groups, there was a significant trend in prescribing less vancomycin with increasing age (P < 0.001). As for the rest of the antibiotics, there was no difference in the overall use of macrolides (P = 0.53), cephalosporins (P = 0.84), or carbapenems (P = 0.67) among age groups. Clindamycin was only used in 9 (2%) out of 392 patients. None of the patients had an aminoglycoside or a sulfa drug prescribed. We also found no difference in terms of antibiotic choice or use of combination therapy among the 3 hospitals (P = 0.78, and P = 0.52; respectively).

Figure 1

Antibiotic choices were influenced by severity of illness. There was an inverse relationship between PSI classes and the use of either fluoroquinolones or ceftriaxone plus azithromycin (P = 0.02) (Figure 2). Patients with higher acuity of illness were more likely to receive combination regimens that include vancomycin plus piperacillin/tazobactam than those with lower acuity of illness (P < 0.001). Neither the comorbidity index nor the ADL scores had a significant impact on the use of combination therapy (P = 0.49 and P = 0.2; respectively). There was a trend toward association between increasing ADL score and the use of vancomycin plus piperacillin/tazobactam but it did not reach statistical significance (P = 0.06). Of interest, patients who were admitted on the University‐affiliated service were more likely to receive combination therapy than those who were under the care of private service (P < 0.001) (Figure 3). Ceftriaxone plus azithromycin accounted for the majority of combination regimens irrespective of physicians' affiliation.

Figure 2

Figure 3

Overall, there were more patients who received antibiotic therapy in compliance with the 2003 IDSA guidelines6 compared with the 2005 ATS/IDSA guidelines7 (65% vs. 19%, respectively; P < 0.001). A positive correlation was noted between severity of illness and adherence to the 2005 ATS/IDSA antimicrobial recommendations (P = 0.02). However, neither the burden of comorbidities nor the functional status was associated with the use of guidelines (P = 0.76 and P = 0.43; respectively).

Duration of therapy ranged from 3 to 21 days with a median of 8 days. The choice of antibiotics, burden of comorbidities, DNR status, or PSI scores had no correlation with antibiotic duration. Only the presence of bacteremia was associated with more than 8 days of antibiotic duration (P < 0.001) (Figure 4). On average, bacteremic patients received 10.1 3.3 (range, 6‐21) days of antimicrobial therapy compared to 7.8 4.1 (range, 319) days for nonbacteremic cases (P < 0.001). During the course of hospitalization, change in antibiotics occurred in 35 (9%) out of the 392 patients, with the majority of substitutions affecting those who were initially prescribed a regimen that included vancomycin plus piperacillin/tazobactam. In these cases, patients were most commonly switched to fluoroquinolones (n = 20), followed by cephalosporins (n = 11).

Figure 4

Discussion

Our study suggests that antimicrobial selection among hospitalized nursing homes patients with pneumonia is influenced by patients' age, severity of illness, and provider's academic affiliation.

This is the first comprehensive study, to our knowledge, to report on the type, distribution, and pattern of antimicrobials prescribed among institutionalized patients requiring hospital admission. Various treatment regimens have been investigated in the last 2 decades using both retrospective and prospective randomized clinical trials to examine the efficacy and safety of parenteral and oral antibiotics in nursing homes.1316 However, there are no randomized controlled clinical trials for the treatment of hospitalized NHAP on which to base treatment recommendations. For some healthcare providers, the treatment parallels the coverage of patients with community‐acquired pneumonia; for others, broad‐spectrum coverage is the norm. In the absence of validated guidelines, the present investigation shows that prescription patterns varied across demographic and clinical characteristics. Fluoroquinolones were the preferred agents for the initial therapy of NHAP across all age groups, probably because of their single daily dosing, broad spectrum coverage against typical and atypical pathogens, and favorable side effect profile. Conversely, the use of vancomycin tended to decline in older age groups. This decline could be attributed to the need for frequent monitoring of trough levels when venous access can be difficult, lack of oral formulation, or potential toxicity. Further studies are needed to examine the validity of this pattern.

To our knowledge, compliance with guidelines regarding treatment of NHAP has not been previously reported. Despite recent studies suggesting that adherence to community‐acquired pneumonia guidelines resulted in reduced need for hospitalization, shorter stays, and lower mortality,1721 our findings indicated a rather low compliance with the most recently published guidelines. Potential reasons for the low levels of compliance include lack of awareness, time lag for the information to be disseminated in the medical community, lack of endorsement by local opinion leaders, or local barriers to implementation of these guidelines. Unfortunately, little is known about physicians' familiarity and attitude toward NHAP guidelines use. Efforts to improve the effectiveness of pneumonia care will depend on future studies aiming at identifying factors that influence nonadherence.

Severity of illness had a significant influence on the prescription pattern of antimicrobial therapy. As the PSI increased, treatment with a fluoroquinolone or with combination therapy of nonpseudomonal third‐generation cephalosporin plus macrolide was replaced by a broader spectrum of antimicrobial coverage. We believe that healthcare providers' prescriptions may be influenced by the recommendations of the ATS guidelines for the treatment of health care associated pneumonia,7 in which antimicrobial therapy for severely ill patients admitted from long‐term care facilities is directed toward multidrug resistant pathogens. The validity of this practice, however, remains the subject of intense debate,2225 driven by the absence of randomized trials showing improved morbidity and mortality.

Few formal clinical trials exist to guide the length of therapy of hospitalized patients with NHAP. The usual recommendation ranges from 7 to 14 days.16, 26 The median duration of 8 days observed in the current study is consistent with length of therapy advocated in the literature.16 Yet, prolonging antibiotic duration has been suggested when clinical severity of illness is high, comorbid illnesses are multiple, and expected resolution is delayed.27 Arguing against such a practice is evidence from meta‐analysis,28 expert reviews,29 and clinical investigation.30 Prescribing principles are nevertheless unlikely to induce substantial change unless their dissemination and promotion is sustained through intensive continuing educational programs for physicians and pharmacists.3133

Our study has a number of limitations. First, the cohort group described in this investigation consists of institutionalized patients in Western New York and hence the antibiotic prescribing patterns may vary in other locations. Second, we did not have adequate microbial information to fully assess the appropriateness of antimicrobial therapy. Third, the absence of microbial etiology may have resulted in incorrect identification of patients with pneumonia. Further, retrospective data extraction is notoriously imperfect, and pneumonia cases may have been missed because of either coding errors or atypical manifestations. However, we have used strict inclusion criteria in to minimize any potential bias. Fourth, the results of this study describe patterns of antibiotic utilization in the treatment of NHAP but do not provide reasoning for such a practice. The rationale behind these practices can only be discerned by a survey of healthcare providers.

In conclusion, we have observed in this study a poor compliance with the current guidelines for the treatment of NHAP. It is generally accepted that physicians' prescribing habits are influenced by their understanding of the pathophysiology and epidemiology of the infection being treated, as well as the pharmacology and spectrum of available antimicrobials. In the absence of outcome data, translation of this knowledge into practice may be influenced by a number of factors, such as the physician's preference, the academic milieu in which the practice occurs, and more importantly, by the patients' clinical condition.

A 62‐year‐old man with hypertension, diabetes mellitus, and coronary artery disease (CAD), on peritoneal dialysis, presented with a nonhealing left lower extremity ulcer (Figure 1). Treatment with empiric antibiotics showed no improvement and cultures remained persistently negative. A surgical specimen revealed pathological changes consistent with calciphylaxis (Figures 2 and 3).

Figure 1

Figure 2

Figure 3

With a mortality between 30% and 80% and a 5‐year survival of 40%,1‐3 calciphylaxis, or calcific uremic arteriolopathy, is devastating. Dialysis and a calcium‐phosphate product above 60 mg²/dL2 increased the index of suspicion (our patient = 70).4 As visual findings may resemble vasculitis or atherosclerotic vascular lesions, biopsy remains the mainstay of diagnosis. Findings include intimal fibrosis, medial calcification, panniculitis, and fat necrosis.5

Management involves aggressive phosphate binding, preventing superinfection, and surgical debridement.6 The evidence for newer therapies (sodium thiosulfate, cinacalcet) appears promising,7‐10 while the benefit of parathyroidectomy is equivocal.11 Despite therapy, our patient developed new lesions (right lower extremity, penis) and opted for hospice services.

A 62‐year‐old man with hypertension, diabetes mellitus, and coronary artery disease (CAD), on peritoneal dialysis, presented with a nonhealing left lower extremity ulcer (Figure 1). Treatment with empiric antibiotics showed no improvement and cultures remained persistently negative. A surgical specimen revealed pathological changes consistent with calciphylaxis (Figures 2 and 3).

Figure 1

Figure 2

Figure 3

With a mortality between 30% and 80% and a 5‐year survival of 40%,1‐3 calciphylaxis, or calcific uremic arteriolopathy, is devastating. Dialysis and a calcium‐phosphate product above 60 mg²/dL2 increased the index of suspicion (our patient = 70).4 As visual findings may resemble vasculitis or atherosclerotic vascular lesions, biopsy remains the mainstay of diagnosis. Findings include intimal fibrosis, medial calcification, panniculitis, and fat necrosis.5

Management involves aggressive phosphate binding, preventing superinfection, and surgical debridement.6 The evidence for newer therapies (sodium thiosulfate, cinacalcet) appears promising,7‐10 while the benefit of parathyroidectomy is equivocal.11 Despite therapy, our patient developed new lesions (right lower extremity, penis) and opted for hospice services.

A 62‐year‐old man with hypertension, diabetes mellitus, and coronary artery disease (CAD), on peritoneal dialysis, presented with a nonhealing left lower extremity ulcer (Figure 1). Treatment with empiric antibiotics showed no improvement and cultures remained persistently negative. A surgical specimen revealed pathological changes consistent with calciphylaxis (Figures 2 and 3).

Figure 1

Figure 2

Figure 3

With a mortality between 30% and 80% and a 5‐year survival of 40%,1‐3 calciphylaxis, or calcific uremic arteriolopathy, is devastating. Dialysis and a calcium‐phosphate product above 60 mg²/dL2 increased the index of suspicion (our patient = 70).4 As visual findings may resemble vasculitis or atherosclerotic vascular lesions, biopsy remains the mainstay of diagnosis. Findings include intimal fibrosis, medial calcification, panniculitis, and fat necrosis.5

Management involves aggressive phosphate binding, preventing superinfection, and surgical debridement.6 The evidence for newer therapies (sodium thiosulfate, cinacalcet) appears promising,7‐10 while the benefit of parathyroidectomy is equivocal.11 Despite therapy, our patient developed new lesions (right lower extremity, penis) and opted for hospice services.