IDWeek 2011

BOSTON – Combination therapy with raltegravir is more effective than efavirenz-based therapy in treatment-naive HIV-1–infected patients, according to data from the ongoing phase III STARTMRK study.

The only drug in the integrase inhibitor class approved for the treatment of HIV-1 infection as part of combination antiretroviral therapy, raltegravir also appears to be better tolerated than efavirenz and has a more favorable metabolic profile, according to 4 years of follow-up data presented by Dr. Edwin DeJesus at the annual meeting of the Infectious Diseases Society of America.

The double-blind, active-controlled, noninferiority study randomized 563 patients to receive either 400 mg raltegravir (Isentress) twice daily or 600 mg efavirenz (Sustiva) once daily, both in combination with coformulated tenofovir and emtricitabine (Truvada), said Dr. DeJesus of the Orlando Immunology Center. Of the 280 patients randomized to raltegravir, 223 (80%) remained in treatment through week 192, as did 197 (70%) of the 282 randomized to efavirenz, he said.

Previously reported study results showed the percentage of patients with less than 50 copies/mL HIV RNA, the primary efficacy measure, to be 86% and 82% for the raltegravir and efavirenz groups, respectively, at 48 weeks and 81% and 79%, respectively, at 96 weeks, Dr. DeJesus said.

At 192 weeks, the proportion of patients who met that target viral load reduction was 214 of 280 in the raltegravir group (76%) and 189 of 282 in the efavirenz group (67%), he reported.

The immunological effect was more pronounced in the raltegravir group, as evidenced by a mean change from baseline in CD4 cell count of 360.7 cells/mm³, compared with 300.9 cells/mm³ in the efavirenz group, he said.

With respect to metabolic parameters, the mean change from baseline in the total cholesterol-to-high-density lipoprotein (HDL) cholesterol at week 192 was –0.17 for the raltegravir group and 0.02 for the efavirenz group, Dr. DeJesus said. The raltegravir regimen also produced less mean change in the individual parameters of total cholesterol, HDL cholesterol, low-density lipoprotein cholesterol, triglycerides, and glucose, he said.

The rate of clinical adverse events, which included diarrhea, nausea, fatigue, dizziness, headache, abnormal dreams, insomnia, nightmares, and rash, was similar overall between both groups, however, significantly fewer drug-related adverse events were observed in the raltegravir group, with a total of 141 (50%), compared with 226 (80%) in the efavirenz patients, according to Dr. DeJesus. There was no significant difference between the two groups in the number of patients who discontinued treatment as a consequence of clinical adverse events, he said.

Based on the findings, "the long-term tolerability and metabolic profile of the integrase-based regimen appear favorable," Dr. DeJesus said. The results are also a good gauge of the evolution of HIV management. "For a long time, we were used to studies that gave us 48-week data, but HIV patients are living much longer now, so we need data that show how these treatments work over the long term," he said. The STARTMRK study is unique in that it has maintained its blinding and will continue to be blinded for 5 years, he added.

Dr. DeJesus disclosed financial relationships with Merck, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Tibotec, Pfizer, Hoffman-La Roche, Achillion, Avexa, and Talmed. The study was sponsored by Merck.

BOSTON – Combination therapy with raltegravir is more effective than efavirenz-based therapy in treatment-naive HIV-1–infected patients, according to data from the ongoing phase III STARTMRK study.

The only drug in the integrase inhibitor class approved for the treatment of HIV-1 infection as part of combination antiretroviral therapy, raltegravir also appears to be better tolerated than efavirenz and has a more favorable metabolic profile, according to 4 years of follow-up data presented by Dr. Edwin DeJesus at the annual meeting of the Infectious Diseases Society of America.

The double-blind, active-controlled, noninferiority study randomized 563 patients to receive either 400 mg raltegravir (Isentress) twice daily or 600 mg efavirenz (Sustiva) once daily, both in combination with coformulated tenofovir and emtricitabine (Truvada), said Dr. DeJesus of the Orlando Immunology Center. Of the 280 patients randomized to raltegravir, 223 (80%) remained in treatment through week 192, as did 197 (70%) of the 282 randomized to efavirenz, he said.

Previously reported study results showed the percentage of patients with less than 50 copies/mL HIV RNA, the primary efficacy measure, to be 86% and 82% for the raltegravir and efavirenz groups, respectively, at 48 weeks and 81% and 79%, respectively, at 96 weeks, Dr. DeJesus said.

At 192 weeks, the proportion of patients who met that target viral load reduction was 214 of 280 in the raltegravir group (76%) and 189 of 282 in the efavirenz group (67%), he reported.

The immunological effect was more pronounced in the raltegravir group, as evidenced by a mean change from baseline in CD4 cell count of 360.7 cells/mm³, compared with 300.9 cells/mm³ in the efavirenz group, he said.

With respect to metabolic parameters, the mean change from baseline in the total cholesterol-to-high-density lipoprotein (HDL) cholesterol at week 192 was –0.17 for the raltegravir group and 0.02 for the efavirenz group, Dr. DeJesus said. The raltegravir regimen also produced less mean change in the individual parameters of total cholesterol, HDL cholesterol, low-density lipoprotein cholesterol, triglycerides, and glucose, he said.

The rate of clinical adverse events, which included diarrhea, nausea, fatigue, dizziness, headache, abnormal dreams, insomnia, nightmares, and rash, was similar overall between both groups, however, significantly fewer drug-related adverse events were observed in the raltegravir group, with a total of 141 (50%), compared with 226 (80%) in the efavirenz patients, according to Dr. DeJesus. There was no significant difference between the two groups in the number of patients who discontinued treatment as a consequence of clinical adverse events, he said.

Based on the findings, "the long-term tolerability and metabolic profile of the integrase-based regimen appear favorable," Dr. DeJesus said. The results are also a good gauge of the evolution of HIV management. "For a long time, we were used to studies that gave us 48-week data, but HIV patients are living much longer now, so we need data that show how these treatments work over the long term," he said. The STARTMRK study is unique in that it has maintained its blinding and will continue to be blinded for 5 years, he added.

Dr. DeJesus disclosed financial relationships with Merck, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Tibotec, Pfizer, Hoffman-La Roche, Achillion, Avexa, and Talmed. The study was sponsored by Merck.

BOSTON – Combination therapy with raltegravir is more effective than efavirenz-based therapy in treatment-naive HIV-1–infected patients, according to data from the ongoing phase III STARTMRK study.

The only drug in the integrase inhibitor class approved for the treatment of HIV-1 infection as part of combination antiretroviral therapy, raltegravir also appears to be better tolerated than efavirenz and has a more favorable metabolic profile, according to 4 years of follow-up data presented by Dr. Edwin DeJesus at the annual meeting of the Infectious Diseases Society of America.

The double-blind, active-controlled, noninferiority study randomized 563 patients to receive either 400 mg raltegravir (Isentress) twice daily or 600 mg efavirenz (Sustiva) once daily, both in combination with coformulated tenofovir and emtricitabine (Truvada), said Dr. DeJesus of the Orlando Immunology Center. Of the 280 patients randomized to raltegravir, 223 (80%) remained in treatment through week 192, as did 197 (70%) of the 282 randomized to efavirenz, he said.

Previously reported study results showed the percentage of patients with less than 50 copies/mL HIV RNA, the primary efficacy measure, to be 86% and 82% for the raltegravir and efavirenz groups, respectively, at 48 weeks and 81% and 79%, respectively, at 96 weeks, Dr. DeJesus said.

At 192 weeks, the proportion of patients who met that target viral load reduction was 214 of 280 in the raltegravir group (76%) and 189 of 282 in the efavirenz group (67%), he reported.

The immunological effect was more pronounced in the raltegravir group, as evidenced by a mean change from baseline in CD4 cell count of 360.7 cells/mm³, compared with 300.9 cells/mm³ in the efavirenz group, he said.

With respect to metabolic parameters, the mean change from baseline in the total cholesterol-to-high-density lipoprotein (HDL) cholesterol at week 192 was –0.17 for the raltegravir group and 0.02 for the efavirenz group, Dr. DeJesus said. The raltegravir regimen also produced less mean change in the individual parameters of total cholesterol, HDL cholesterol, low-density lipoprotein cholesterol, triglycerides, and glucose, he said.

The rate of clinical adverse events, which included diarrhea, nausea, fatigue, dizziness, headache, abnormal dreams, insomnia, nightmares, and rash, was similar overall between both groups, however, significantly fewer drug-related adverse events were observed in the raltegravir group, with a total of 141 (50%), compared with 226 (80%) in the efavirenz patients, according to Dr. DeJesus. There was no significant difference between the two groups in the number of patients who discontinued treatment as a consequence of clinical adverse events, he said.

Based on the findings, "the long-term tolerability and metabolic profile of the integrase-based regimen appear favorable," Dr. DeJesus said. The results are also a good gauge of the evolution of HIV management. "For a long time, we were used to studies that gave us 48-week data, but HIV patients are living much longer now, so we need data that show how these treatments work over the long term," he said. The STARTMRK study is unique in that it has maintained its blinding and will continue to be blinded for 5 years, he added.

Dr. DeJesus disclosed financial relationships with Merck, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Tibotec, Pfizer, Hoffman-La Roche, Achillion, Avexa, and Talmed. The study was sponsored by Merck.

BOSTON – A small but concerning recent surge in cases of invasive infection with Haemophilus influenzae serotype a among Native Alaskan children appears to be an "emerging" infection, reported epidemiologists from the Centers for Disease Control and Prevention.

CDC epidemiologists first identified an Alaskan invasive infection by H. influenzae serotype a (Hia) in 2002, and by mid-October 2011 the tally stood at 27 cases in children younger than 5 years old and is still rising, with 13 of the cases clustered in 2010 and 2011, Dr. Michael Bruce said at the annual meeting of the Infectious Diseases Society of America.

Most of the cases have been in children younger than 5 years old, in Alaskan Native children, and most also have been clustered in a specific region of western Alaska. Over the past 2 years, the Hia incidence rate among all Alaskan Native children younger than 5 years old has been 15.4 cases per 100,000, and among these children specifically in the western area, the rate has approached about 200 cases per 100,0000, "comparable to Haemophilus influenzae type b [Hib] in the pre-vaccine era," he said.

"It’s alarming to us that we have this many cases" in 2010 and 2011, he said in an interview. "It is particularly alarming because these children are quite ill. Their symptoms are very similar to what we saw in the past with Hib." The most common presentation of invasive disease has been meningitis in 41% of cases, followed by pneumonia with bacteremia in 26%, and septic arthritis in 22%. Hospitalization was required for 89% of the 27 cases he reviewed since 2002, and two children died, as well as a third death that occurred in a recent case not included in this series, he said.

"This is a serious disease, similar to Hib," said Dr. Bruce, epidemiology team leader in the Artic Investigations Program of the CDC in Anchorage. But, "I don’t think these [Hia cases] are temporally related to use of the Hib vaccine," which virtually eliminated Hib as a cause of invasive infections since its introduction 20 years ago.

Most of the cases have been in children younger than 5 years old, in Alaskan Native children, and most also have been clustered in a specific region of western Alaska.

The 27 invasive Hia cases Dr. Bruce reviewed since it first appeared in children younger than 5 years in 2002 had an average age of 0.7 years old, with a range of 4 months to 2.4 years old, and with 63% of the cases in boys. A total of 25 of the 27 cases (93%) were in Alaskan Native children, and 93% of the cases had been appropriately vaccinated for Hib. In all, 23 of the 27 cases (85%) occurred in western Alaska.

The CDC has no recommendations for treating non-serotype b invasive H. influenzae infections, nor does it have a recommended regimen for prophylactic treatment of close contacts of index cases. Physicians in Alaska have generally been treating invasive Hia infections as they would invasive infections by Hib, and roughly half of the Alaskan physicians who have managed the invasive Hia cases have dispensed preventive antibiotics to close contacts following the old Hib recommendations. So far, epidemiologic investigations in Alaska failed to identify any episodes of secondary Hia infections transmitted from an identified index case, Dr. Bruce said.

Recent reports of Hia clusters also have come from a handful of other North American locations, Dr. Bruce said: the northern Canadian Territories; northern areas of three Canadian Provinces – British Columbia, Manitoba, and Ontario; Utah; and in Navajo and White Mountain Apache communities in the southwestern United States. It is not clear whether these clusters have any link to what Dr. Bruce has seen in Alaska.

But he urged vigilance for Hia throughout North America. "Testing for [Hia in children with invasive bacterial infections] is a good idea, especially because it is being identified in more and more places," Dr. Bruce said.

But he and his associates retested surveillance specimens of H. influenzae collected from invasive pediatric Alaskan cases starting from 1980 and were unable to find any evidence of invasive Hia that predated the first known Alaskan case in 2002. "It looks to me like we did not have any cases of invasive Hia in Alaska until 2002," he said.

Dr. Bruce said that he had no relevant financial disclosures.

BOSTON – A small but concerning recent surge in cases of invasive infection with Haemophilus influenzae serotype a among Native Alaskan children appears to be an "emerging" infection, reported epidemiologists from the Centers for Disease Control and Prevention.

CDC epidemiologists first identified an Alaskan invasive infection by H. influenzae serotype a (Hia) in 2002, and by mid-October 2011 the tally stood at 27 cases in children younger than 5 years old and is still rising, with 13 of the cases clustered in 2010 and 2011, Dr. Michael Bruce said at the annual meeting of the Infectious Diseases Society of America.

Most of the cases have been in children younger than 5 years old, in Alaskan Native children, and most also have been clustered in a specific region of western Alaska. Over the past 2 years, the Hia incidence rate among all Alaskan Native children younger than 5 years old has been 15.4 cases per 100,000, and among these children specifically in the western area, the rate has approached about 200 cases per 100,0000, "comparable to Haemophilus influenzae type b [Hib] in the pre-vaccine era," he said.

"It’s alarming to us that we have this many cases" in 2010 and 2011, he said in an interview. "It is particularly alarming because these children are quite ill. Their symptoms are very similar to what we saw in the past with Hib." The most common presentation of invasive disease has been meningitis in 41% of cases, followed by pneumonia with bacteremia in 26%, and septic arthritis in 22%. Hospitalization was required for 89% of the 27 cases he reviewed since 2002, and two children died, as well as a third death that occurred in a recent case not included in this series, he said.

"This is a serious disease, similar to Hib," said Dr. Bruce, epidemiology team leader in the Artic Investigations Program of the CDC in Anchorage. But, "I don’t think these [Hia cases] are temporally related to use of the Hib vaccine," which virtually eliminated Hib as a cause of invasive infections since its introduction 20 years ago.

Most of the cases have been in children younger than 5 years old, in Alaskan Native children, and most also have been clustered in a specific region of western Alaska.

The 27 invasive Hia cases Dr. Bruce reviewed since it first appeared in children younger than 5 years in 2002 had an average age of 0.7 years old, with a range of 4 months to 2.4 years old, and with 63% of the cases in boys. A total of 25 of the 27 cases (93%) were in Alaskan Native children, and 93% of the cases had been appropriately vaccinated for Hib. In all, 23 of the 27 cases (85%) occurred in western Alaska.

The CDC has no recommendations for treating non-serotype b invasive H. influenzae infections, nor does it have a recommended regimen for prophylactic treatment of close contacts of index cases. Physicians in Alaska have generally been treating invasive Hia infections as they would invasive infections by Hib, and roughly half of the Alaskan physicians who have managed the invasive Hia cases have dispensed preventive antibiotics to close contacts following the old Hib recommendations. So far, epidemiologic investigations in Alaska failed to identify any episodes of secondary Hia infections transmitted from an identified index case, Dr. Bruce said.

Recent reports of Hia clusters also have come from a handful of other North American locations, Dr. Bruce said: the northern Canadian Territories; northern areas of three Canadian Provinces – British Columbia, Manitoba, and Ontario; Utah; and in Navajo and White Mountain Apache communities in the southwestern United States. It is not clear whether these clusters have any link to what Dr. Bruce has seen in Alaska.

But he urged vigilance for Hia throughout North America. "Testing for [Hia in children with invasive bacterial infections] is a good idea, especially because it is being identified in more and more places," Dr. Bruce said.

But he and his associates retested surveillance specimens of H. influenzae collected from invasive pediatric Alaskan cases starting from 1980 and were unable to find any evidence of invasive Hia that predated the first known Alaskan case in 2002. "It looks to me like we did not have any cases of invasive Hia in Alaska until 2002," he said.

Dr. Bruce said that he had no relevant financial disclosures.

BOSTON – A small but concerning recent surge in cases of invasive infection with Haemophilus influenzae serotype a among Native Alaskan children appears to be an "emerging" infection, reported epidemiologists from the Centers for Disease Control and Prevention.

CDC epidemiologists first identified an Alaskan invasive infection by H. influenzae serotype a (Hia) in 2002, and by mid-October 2011 the tally stood at 27 cases in children younger than 5 years old and is still rising, with 13 of the cases clustered in 2010 and 2011, Dr. Michael Bruce said at the annual meeting of the Infectious Diseases Society of America.

Most of the cases have been in children younger than 5 years old, in Alaskan Native children, and most also have been clustered in a specific region of western Alaska. Over the past 2 years, the Hia incidence rate among all Alaskan Native children younger than 5 years old has been 15.4 cases per 100,000, and among these children specifically in the western area, the rate has approached about 200 cases per 100,0000, "comparable to Haemophilus influenzae type b [Hib] in the pre-vaccine era," he said.

"It’s alarming to us that we have this many cases" in 2010 and 2011, he said in an interview. "It is particularly alarming because these children are quite ill. Their symptoms are very similar to what we saw in the past with Hib." The most common presentation of invasive disease has been meningitis in 41% of cases, followed by pneumonia with bacteremia in 26%, and septic arthritis in 22%. Hospitalization was required for 89% of the 27 cases he reviewed since 2002, and two children died, as well as a third death that occurred in a recent case not included in this series, he said.

"This is a serious disease, similar to Hib," said Dr. Bruce, epidemiology team leader in the Artic Investigations Program of the CDC in Anchorage. But, "I don’t think these [Hia cases] are temporally related to use of the Hib vaccine," which virtually eliminated Hib as a cause of invasive infections since its introduction 20 years ago.

Most of the cases have been in children younger than 5 years old, in Alaskan Native children, and most also have been clustered in a specific region of western Alaska.

The 27 invasive Hia cases Dr. Bruce reviewed since it first appeared in children younger than 5 years in 2002 had an average age of 0.7 years old, with a range of 4 months to 2.4 years old, and with 63% of the cases in boys. A total of 25 of the 27 cases (93%) were in Alaskan Native children, and 93% of the cases had been appropriately vaccinated for Hib. In all, 23 of the 27 cases (85%) occurred in western Alaska.

The CDC has no recommendations for treating non-serotype b invasive H. influenzae infections, nor does it have a recommended regimen for prophylactic treatment of close contacts of index cases. Physicians in Alaska have generally been treating invasive Hia infections as they would invasive infections by Hib, and roughly half of the Alaskan physicians who have managed the invasive Hia cases have dispensed preventive antibiotics to close contacts following the old Hib recommendations. So far, epidemiologic investigations in Alaska failed to identify any episodes of secondary Hia infections transmitted from an identified index case, Dr. Bruce said.

Recent reports of Hia clusters also have come from a handful of other North American locations, Dr. Bruce said: the northern Canadian Territories; northern areas of three Canadian Provinces – British Columbia, Manitoba, and Ontario; Utah; and in Navajo and White Mountain Apache communities in the southwestern United States. It is not clear whether these clusters have any link to what Dr. Bruce has seen in Alaska.

But he urged vigilance for Hia throughout North America. "Testing for [Hia in children with invasive bacterial infections] is a good idea, especially because it is being identified in more and more places," Dr. Bruce said.

But he and his associates retested surveillance specimens of H. influenzae collected from invasive pediatric Alaskan cases starting from 1980 and were unable to find any evidence of invasive Hia that predated the first known Alaskan case in 2002. "It looks to me like we did not have any cases of invasive Hia in Alaska until 2002," he said.

Dr. Bruce said that he had no relevant financial disclosures.

BOSTON – The acellular pertussis vaccine’s failure to deliver durable infection protection to children aged 7-10 years led to the 2010 California pertussis epidemic, and prompted infectious diseases experts to question the current schedule of childhood pertussis vaccination.

"An increase in the risk of pertussis is occurring in the time since completion of the five-dose DTaP [diphtheria, tetanus, acellular pertussis] series, with similar trends seen in California, Minnesota, and Oregon," Sara Tartof, Ph.D., said at the annual meeting of the Infectious Diseases Society of America.

"Continued evaluation of DTaP duration of protection is needed to determine the appropriateness of timing of pertussis vaccinations," said Dr. Tartof, an epidemic intelligence officer in the Centers for Disease Control and Prevention’s National Center for Immunization and Respiratory Diseases in Atlanta.

Dr. Tartof and a second CDC researcher presented results from two independent studies that both showed children faced a substantially increased rate of pertussis infection 4 or more years out from their fifth and final childhood vaccination, which these days usually occurs when U.S. children are 4 years old. Recent surges in U.S. pertussis cases, which began in 2005, and then spiked even higher in 2010, implicated the acellular vaccine as the cause.

"It certainly caused the 2010 California epidemic, and it happened in Minnesota and Oregon, too. Waning immunity with acellular pertussis led to greater vulnerability in 7- to 10-year-olds," commented Dr. Kathryn M. Edwards, Sarah H. Sell professor of pediatrics and director of the Vaccine Research Program at Vanderbilt University in Nashville, Tenn.

"The durability of protection with the acellular vaccine is not as good as with the whole cell vaccine, but the problem with the whole-cell vaccine was that it was quite reactive," causing local reactions and fevers, she said in an interview.

"At this point, people would not accept the whole-cell vaccine," which means something needs to be done with the acellular vaccine, she said. Possible options include additional boosted vaccinations, or moving administration of the fifth childhood dose of DTaP from 4-year-olds to 6-year-olds.

The CDC’s recommended vaccination schedule already calls for delivery of the fifth dose at ages 4-6 years, but in reality most U.S. children receive it at age 4 when they enter preschool.

Pertussis "is a difficult disease. Even after five doses, susceptibility increases after 1 year. It’s really a toughie," said Dr. Sarah Long, professor of pediatrics at Drexel University and chief of infectious diseases at St. Christopher’s Hospital for Children, both in Philadelphia.

One of the CDC studies focused on pertussis cases that appeared in any of 15 California counties during the state’s 2010 epidemic. Chart reviews by CDC researchers identified 682 pertussis cases among children aged 4-10 years, and 2,016 unmatched controls from the same age group and counties. Roughly 70% of the children who had received all five scheduled doses had received their fifth dose at 4 years, and about 30% received their fifth dose at 5 years, with less than 1% of the children receiving their last dose at 6 years. One percent of the control children and 8% of the cases had received no doses of DTaP.

An analysis of the time elapsed following the fifth dose relative to when pertussis infection occurred showed that after 2 years the vaccine’s efficacy was 92% of what it had been during the first year following the fifth dose, after 3 years the efficacy fell to 87%, after 4 years it dropped to 83%, and after 5 years the vaccine efficacy was 71% below where it stood immediately after the fifth dose, reported Lara K. Misegades, Ph.D., an epidemic intelligence officer also with the CDC’s National Center for Immunization and Respiratory Diseases.

This translated into a 15-fold higher relative risk for infection in children during the sixth year following their final dose, compared with children during the first 12 months following their fifth vaccine dose, Dr. Tartof said.

The second CDC study, presented by Dr. Tartof, used data collected by the immunization registries of Minnesota and Oregon for children immunized against pertussis during 1998-2003, and data on pertussis cases in these two states from reports to the CDC through the National Notifiable Disease Surveillance System. This analysis included 224,378 fully immunized children and 521 pertussis cases in Minnesota, and 179,011 fully immunized children and 99 reported cases in Oregon.

Dr. Tartof and her associates used these data to calculate a pertussis incidence rate during each year following delivery of the fifth childhood dose, and reported the relative risk for infection during each follow-up year relative to the first 12 months after the fifth dose. By the sixth year, the risk was seven-fold higher in Minnesota, and four-fold higher in Oregon, she reported. The risk for infection rose steadily during each year following the fifth dose.

Overall, the data from California, Minnesota, and Oregon showed "similar trends in three different settings, using two different study designs," lending added credibility to the finding that pertussis immunity waned with time, Dr. Tartof said.

Dr. Tartof, Dr. Edwards, Dr. Long, and Dr. Misegades all said that they had no relevant financial disclosures.

BOSTON – The acellular pertussis vaccine’s failure to deliver durable infection protection to children aged 7-10 years led to the 2010 California pertussis epidemic, and prompted infectious diseases experts to question the current schedule of childhood pertussis vaccination.

"An increase in the risk of pertussis is occurring in the time since completion of the five-dose DTaP [diphtheria, tetanus, acellular pertussis] series, with similar trends seen in California, Minnesota, and Oregon," Sara Tartof, Ph.D., said at the annual meeting of the Infectious Diseases Society of America.

"Continued evaluation of DTaP duration of protection is needed to determine the appropriateness of timing of pertussis vaccinations," said Dr. Tartof, an epidemic intelligence officer in the Centers for Disease Control and Prevention’s National Center for Immunization and Respiratory Diseases in Atlanta.

Dr. Tartof and a second CDC researcher presented results from two independent studies that both showed children faced a substantially increased rate of pertussis infection 4 or more years out from their fifth and final childhood vaccination, which these days usually occurs when U.S. children are 4 years old. Recent surges in U.S. pertussis cases, which began in 2005, and then spiked even higher in 2010, implicated the acellular vaccine as the cause.

"It certainly caused the 2010 California epidemic, and it happened in Minnesota and Oregon, too. Waning immunity with acellular pertussis led to greater vulnerability in 7- to 10-year-olds," commented Dr. Kathryn M. Edwards, Sarah H. Sell professor of pediatrics and director of the Vaccine Research Program at Vanderbilt University in Nashville, Tenn.

"The durability of protection with the acellular vaccine is not as good as with the whole cell vaccine, but the problem with the whole-cell vaccine was that it was quite reactive," causing local reactions and fevers, she said in an interview.

"At this point, people would not accept the whole-cell vaccine," which means something needs to be done with the acellular vaccine, she said. Possible options include additional boosted vaccinations, or moving administration of the fifth childhood dose of DTaP from 4-year-olds to 6-year-olds.

The CDC’s recommended vaccination schedule already calls for delivery of the fifth dose at ages 4-6 years, but in reality most U.S. children receive it at age 4 when they enter preschool.

Pertussis "is a difficult disease. Even after five doses, susceptibility increases after 1 year. It’s really a toughie," said Dr. Sarah Long, professor of pediatrics at Drexel University and chief of infectious diseases at St. Christopher’s Hospital for Children, both in Philadelphia.

One of the CDC studies focused on pertussis cases that appeared in any of 15 California counties during the state’s 2010 epidemic. Chart reviews by CDC researchers identified 682 pertussis cases among children aged 4-10 years, and 2,016 unmatched controls from the same age group and counties. Roughly 70% of the children who had received all five scheduled doses had received their fifth dose at 4 years, and about 30% received their fifth dose at 5 years, with less than 1% of the children receiving their last dose at 6 years. One percent of the control children and 8% of the cases had received no doses of DTaP.

An analysis of the time elapsed following the fifth dose relative to when pertussis infection occurred showed that after 2 years the vaccine’s efficacy was 92% of what it had been during the first year following the fifth dose, after 3 years the efficacy fell to 87%, after 4 years it dropped to 83%, and after 5 years the vaccine efficacy was 71% below where it stood immediately after the fifth dose, reported Lara K. Misegades, Ph.D., an epidemic intelligence officer also with the CDC’s National Center for Immunization and Respiratory Diseases.

This translated into a 15-fold higher relative risk for infection in children during the sixth year following their final dose, compared with children during the first 12 months following their fifth vaccine dose, Dr. Tartof said.

The second CDC study, presented by Dr. Tartof, used data collected by the immunization registries of Minnesota and Oregon for children immunized against pertussis during 1998-2003, and data on pertussis cases in these two states from reports to the CDC through the National Notifiable Disease Surveillance System. This analysis included 224,378 fully immunized children and 521 pertussis cases in Minnesota, and 179,011 fully immunized children and 99 reported cases in Oregon.

Dr. Tartof and her associates used these data to calculate a pertussis incidence rate during each year following delivery of the fifth childhood dose, and reported the relative risk for infection during each follow-up year relative to the first 12 months after the fifth dose. By the sixth year, the risk was seven-fold higher in Minnesota, and four-fold higher in Oregon, she reported. The risk for infection rose steadily during each year following the fifth dose.

Overall, the data from California, Minnesota, and Oregon showed "similar trends in three different settings, using two different study designs," lending added credibility to the finding that pertussis immunity waned with time, Dr. Tartof said.

Dr. Tartof, Dr. Edwards, Dr. Long, and Dr. Misegades all said that they had no relevant financial disclosures.

BOSTON – The acellular pertussis vaccine’s failure to deliver durable infection protection to children aged 7-10 years led to the 2010 California pertussis epidemic, and prompted infectious diseases experts to question the current schedule of childhood pertussis vaccination.

"An increase in the risk of pertussis is occurring in the time since completion of the five-dose DTaP [diphtheria, tetanus, acellular pertussis] series, with similar trends seen in California, Minnesota, and Oregon," Sara Tartof, Ph.D., said at the annual meeting of the Infectious Diseases Society of America.

"Continued evaluation of DTaP duration of protection is needed to determine the appropriateness of timing of pertussis vaccinations," said Dr. Tartof, an epidemic intelligence officer in the Centers for Disease Control and Prevention’s National Center for Immunization and Respiratory Diseases in Atlanta.

Dr. Tartof and a second CDC researcher presented results from two independent studies that both showed children faced a substantially increased rate of pertussis infection 4 or more years out from their fifth and final childhood vaccination, which these days usually occurs when U.S. children are 4 years old. Recent surges in U.S. pertussis cases, which began in 2005, and then spiked even higher in 2010, implicated the acellular vaccine as the cause.

"It certainly caused the 2010 California epidemic, and it happened in Minnesota and Oregon, too. Waning immunity with acellular pertussis led to greater vulnerability in 7- to 10-year-olds," commented Dr. Kathryn M. Edwards, Sarah H. Sell professor of pediatrics and director of the Vaccine Research Program at Vanderbilt University in Nashville, Tenn.

"The durability of protection with the acellular vaccine is not as good as with the whole cell vaccine, but the problem with the whole-cell vaccine was that it was quite reactive," causing local reactions and fevers, she said in an interview.

"At this point, people would not accept the whole-cell vaccine," which means something needs to be done with the acellular vaccine, she said. Possible options include additional boosted vaccinations, or moving administration of the fifth childhood dose of DTaP from 4-year-olds to 6-year-olds.

The CDC’s recommended vaccination schedule already calls for delivery of the fifth dose at ages 4-6 years, but in reality most U.S. children receive it at age 4 when they enter preschool.

Pertussis "is a difficult disease. Even after five doses, susceptibility increases after 1 year. It’s really a toughie," said Dr. Sarah Long, professor of pediatrics at Drexel University and chief of infectious diseases at St. Christopher’s Hospital for Children, both in Philadelphia.

One of the CDC studies focused on pertussis cases that appeared in any of 15 California counties during the state’s 2010 epidemic. Chart reviews by CDC researchers identified 682 pertussis cases among children aged 4-10 years, and 2,016 unmatched controls from the same age group and counties. Roughly 70% of the children who had received all five scheduled doses had received their fifth dose at 4 years, and about 30% received their fifth dose at 5 years, with less than 1% of the children receiving their last dose at 6 years. One percent of the control children and 8% of the cases had received no doses of DTaP.

An analysis of the time elapsed following the fifth dose relative to when pertussis infection occurred showed that after 2 years the vaccine’s efficacy was 92% of what it had been during the first year following the fifth dose, after 3 years the efficacy fell to 87%, after 4 years it dropped to 83%, and after 5 years the vaccine efficacy was 71% below where it stood immediately after the fifth dose, reported Lara K. Misegades, Ph.D., an epidemic intelligence officer also with the CDC’s National Center for Immunization and Respiratory Diseases.

This translated into a 15-fold higher relative risk for infection in children during the sixth year following their final dose, compared with children during the first 12 months following their fifth vaccine dose, Dr. Tartof said.

The second CDC study, presented by Dr. Tartof, used data collected by the immunization registries of Minnesota and Oregon for children immunized against pertussis during 1998-2003, and data on pertussis cases in these two states from reports to the CDC through the National Notifiable Disease Surveillance System. This analysis included 224,378 fully immunized children and 521 pertussis cases in Minnesota, and 179,011 fully immunized children and 99 reported cases in Oregon.

Dr. Tartof and her associates used these data to calculate a pertussis incidence rate during each year following delivery of the fifth childhood dose, and reported the relative risk for infection during each follow-up year relative to the first 12 months after the fifth dose. By the sixth year, the risk was seven-fold higher in Minnesota, and four-fold higher in Oregon, she reported. The risk for infection rose steadily during each year following the fifth dose.

Overall, the data from California, Minnesota, and Oregon showed "similar trends in three different settings, using two different study designs," lending added credibility to the finding that pertussis immunity waned with time, Dr. Tartof said.

Dr. Tartof, Dr. Edwards, Dr. Long, and Dr. Misegades all said that they had no relevant financial disclosures.

BOSTON – Vaccination of U.S. children against rotavirus appears to be helping to curb rotavirus infections in adults, according to an analysis of data from more than 3,500 adults seen at one Chicago hospital during 2006-2010.

An analysis of stool bacterial cultures collected from 2,545 patients, aged 18 or older, at Northwestern Memorial Hospital during 2008-2010 showed a 49% drop in the prevalence of rotavirus compared with the prevalence in 988 specimens tested during 2006-2007, Dr. Evan J. Anderson reported in a poster at the meeting.

The finding "strongly suggests an indirect effect of pediatric rotavirus vaccination on rotavirus in adults," he said in the poster.

The timing of the effect correlates with rotavirus vaccine uptake among U.S. children. RotaTeq, the first of the two vaccines now on the U.S. market, received Food and Drug Administration licensing in 2006, but widespread U.S. rotavirus vaccination of children did not reach a high level until 2008, when a second formulation, Rotarix, also received FDA approval, said Dr. Anderson, an infectious diseases physician at Northwestern University and at Children’s Memorial Hospital in Chicago. Currently, more than 70% of U.S. children in the 2- to 6-month-old target age group for the vaccine actually receive it, he said in an interview.

To gauge the impact of widespread rotavirus vaccination on adult disease, Dr. Anderson and his associates reviewed laboratory records at Northwestern Memorial Hospital for bacterial stool cultures from adult specimens during 2006-2010. The data showed a 4.4% rotavirus prevalence rate in specimens taken during 2006-2007, and a 2.2% rate in specimens cultured during 2007-2010, a statistically significant difference.

"It’s a fantastic impact that changes the cost-effectiveness equation of giving rotavirus vaccine to kids, because you’re also protecting their parents and grandparents," Dr. Anderson said. He speculated that adults received protection against infection via a herd effect, with fewer children shedding and spreading rotavirus. The effect is important because "rotavirus is underappreciated as an adult pathogen." The diarrhea and vomiting it causes can have significant effects on adults, especially those with comorbidities, he said.

The evidence reported by Dr. Anderson and his associates corroborates another report of declining rotavirus prevalence among U.S. adults nationally. Researchers at the Centers for Disease Control and Prevention analyzed U.S. hospitalizations for diarrhea during 2000-2008 using data collected in the Nationwide Inpatient Sample. These investigators identified cases with a diagnosis of rotavirus infection by ICD-9-CM codes. The analysis showed that among people aged 15-24 years old, the incidence of rotavirus-associated diarrheal hospitalizations in 2008 was 65% less than in 2000-2006, a statistically significant difference (J. Infec. Dis. 2011;204:980-6). The incidence among adults, aged 25-64, ran 26% lower in 2008 compared with 2000-2006, and 21% lower among those aged 65 and older, but these differences did not reach statistical significance.

In an editorial accompanying the study, Dr. Roger I. Glass, director of the Fogarty International Center of the National Institutes of Health, called the CDC findings "remarkable observations on the indirect effects of the vaccine that could not have been anticipated before the vaccine was introduced" (J. Infec. Dis. 2011;204:975-7).

The CDC report suggests that the findings in Chicago represent what has happened throughout the United States, Dr. Anderson said. "We’re now providing direct, patient-related data that are remarkably similar to what the CDC showed with ICD-9 data, so this is almost certainly representative. There is no reason to think it is limited to just Chicago."

Dr. Anderson said that his study received partial funding from Meridian Biosciences and from Merck, the company that markets the RotaTeq vaccine. Dr. Glass said that he had no other relevant financial disclosures.

BOSTON – Vaccination of U.S. children against rotavirus appears to be helping to curb rotavirus infections in adults, according to an analysis of data from more than 3,500 adults seen at one Chicago hospital during 2006-2010.

An analysis of stool bacterial cultures collected from 2,545 patients, aged 18 or older, at Northwestern Memorial Hospital during 2008-2010 showed a 49% drop in the prevalence of rotavirus compared with the prevalence in 988 specimens tested during 2006-2007, Dr. Evan J. Anderson reported in a poster at the meeting.

The finding "strongly suggests an indirect effect of pediatric rotavirus vaccination on rotavirus in adults," he said in the poster.

The timing of the effect correlates with rotavirus vaccine uptake among U.S. children. RotaTeq, the first of the two vaccines now on the U.S. market, received Food and Drug Administration licensing in 2006, but widespread U.S. rotavirus vaccination of children did not reach a high level until 2008, when a second formulation, Rotarix, also received FDA approval, said Dr. Anderson, an infectious diseases physician at Northwestern University and at Children’s Memorial Hospital in Chicago. Currently, more than 70% of U.S. children in the 2- to 6-month-old target age group for the vaccine actually receive it, he said in an interview.

To gauge the impact of widespread rotavirus vaccination on adult disease, Dr. Anderson and his associates reviewed laboratory records at Northwestern Memorial Hospital for bacterial stool cultures from adult specimens during 2006-2010. The data showed a 4.4% rotavirus prevalence rate in specimens taken during 2006-2007, and a 2.2% rate in specimens cultured during 2007-2010, a statistically significant difference.

"It’s a fantastic impact that changes the cost-effectiveness equation of giving rotavirus vaccine to kids, because you’re also protecting their parents and grandparents," Dr. Anderson said. He speculated that adults received protection against infection via a herd effect, with fewer children shedding and spreading rotavirus. The effect is important because "rotavirus is underappreciated as an adult pathogen." The diarrhea and vomiting it causes can have significant effects on adults, especially those with comorbidities, he said.

The evidence reported by Dr. Anderson and his associates corroborates another report of declining rotavirus prevalence among U.S. adults nationally. Researchers at the Centers for Disease Control and Prevention analyzed U.S. hospitalizations for diarrhea during 2000-2008 using data collected in the Nationwide Inpatient Sample. These investigators identified cases with a diagnosis of rotavirus infection by ICD-9-CM codes. The analysis showed that among people aged 15-24 years old, the incidence of rotavirus-associated diarrheal hospitalizations in 2008 was 65% less than in 2000-2006, a statistically significant difference (J. Infec. Dis. 2011;204:980-6). The incidence among adults, aged 25-64, ran 26% lower in 2008 compared with 2000-2006, and 21% lower among those aged 65 and older, but these differences did not reach statistical significance.

In an editorial accompanying the study, Dr. Roger I. Glass, director of the Fogarty International Center of the National Institutes of Health, called the CDC findings "remarkable observations on the indirect effects of the vaccine that could not have been anticipated before the vaccine was introduced" (J. Infec. Dis. 2011;204:975-7).

The CDC report suggests that the findings in Chicago represent what has happened throughout the United States, Dr. Anderson said. "We’re now providing direct, patient-related data that are remarkably similar to what the CDC showed with ICD-9 data, so this is almost certainly representative. There is no reason to think it is limited to just Chicago."

Dr. Anderson said that his study received partial funding from Meridian Biosciences and from Merck, the company that markets the RotaTeq vaccine. Dr. Glass said that he had no other relevant financial disclosures.

BOSTON – Vaccination of U.S. children against rotavirus appears to be helping to curb rotavirus infections in adults, according to an analysis of data from more than 3,500 adults seen at one Chicago hospital during 2006-2010.

An analysis of stool bacterial cultures collected from 2,545 patients, aged 18 or older, at Northwestern Memorial Hospital during 2008-2010 showed a 49% drop in the prevalence of rotavirus compared with the prevalence in 988 specimens tested during 2006-2007, Dr. Evan J. Anderson reported in a poster at the meeting.

The finding "strongly suggests an indirect effect of pediatric rotavirus vaccination on rotavirus in adults," he said in the poster.

The timing of the effect correlates with rotavirus vaccine uptake among U.S. children. RotaTeq, the first of the two vaccines now on the U.S. market, received Food and Drug Administration licensing in 2006, but widespread U.S. rotavirus vaccination of children did not reach a high level until 2008, when a second formulation, Rotarix, also received FDA approval, said Dr. Anderson, an infectious diseases physician at Northwestern University and at Children’s Memorial Hospital in Chicago. Currently, more than 70% of U.S. children in the 2- to 6-month-old target age group for the vaccine actually receive it, he said in an interview.

To gauge the impact of widespread rotavirus vaccination on adult disease, Dr. Anderson and his associates reviewed laboratory records at Northwestern Memorial Hospital for bacterial stool cultures from adult specimens during 2006-2010. The data showed a 4.4% rotavirus prevalence rate in specimens taken during 2006-2007, and a 2.2% rate in specimens cultured during 2007-2010, a statistically significant difference.

"It’s a fantastic impact that changes the cost-effectiveness equation of giving rotavirus vaccine to kids, because you’re also protecting their parents and grandparents," Dr. Anderson said. He speculated that adults received protection against infection via a herd effect, with fewer children shedding and spreading rotavirus. The effect is important because "rotavirus is underappreciated as an adult pathogen." The diarrhea and vomiting it causes can have significant effects on adults, especially those with comorbidities, he said.

The evidence reported by Dr. Anderson and his associates corroborates another report of declining rotavirus prevalence among U.S. adults nationally. Researchers at the Centers for Disease Control and Prevention analyzed U.S. hospitalizations for diarrhea during 2000-2008 using data collected in the Nationwide Inpatient Sample. These investigators identified cases with a diagnosis of rotavirus infection by ICD-9-CM codes. The analysis showed that among people aged 15-24 years old, the incidence of rotavirus-associated diarrheal hospitalizations in 2008 was 65% less than in 2000-2006, a statistically significant difference (J. Infec. Dis. 2011;204:980-6). The incidence among adults, aged 25-64, ran 26% lower in 2008 compared with 2000-2006, and 21% lower among those aged 65 and older, but these differences did not reach statistical significance.

In an editorial accompanying the study, Dr. Roger I. Glass, director of the Fogarty International Center of the National Institutes of Health, called the CDC findings "remarkable observations on the indirect effects of the vaccine that could not have been anticipated before the vaccine was introduced" (J. Infec. Dis. 2011;204:975-7).

The CDC report suggests that the findings in Chicago represent what has happened throughout the United States, Dr. Anderson said. "We’re now providing direct, patient-related data that are remarkably similar to what the CDC showed with ICD-9 data, so this is almost certainly representative. There is no reason to think it is limited to just Chicago."

Dr. Anderson said that his study received partial funding from Meridian Biosciences and from Merck, the company that markets the RotaTeq vaccine. Dr. Glass said that he had no other relevant financial disclosures.

BOSTON – Serious infections requiring long-term treatment can be managed safely and effectively with outpatient parenteral antimicrobial therapy administered by infusion centers, a study has shown.

In an observational review of data from multiple infectious disease physician office infusion centers (POICs) over a 6-month period, the recurrence and readmission rates for patients treated for bacteremia, endocarditis, and osteomyelitis were low and more favorable than previously observed in similar studies, Dr. Michael P. Dailey reported at the annual meeting of the Infectious Diseases Society of America.

Of 203 patients (mean age 59 years) treated for bacteremia (54), infective endocarditis (26), and osteomyelitis (123) from Jan. 1, 2010, to June 30, 2010, 188 (93%) met the study criteria for clinical success, defined as cured or improved, while 13 (6%) and 19 (9%), respectively, experienced a recurrence within 6 months or required readmission during therapy, said Dr. Dailey of an infectious disease specialist in Roswell, Ga.

By infection type, 50 (93%) of the bacteremia patients, 23 (88%) of the endocarditis patients, and 115 (93%) of the osteomyelitis patients achieved clinical success, while the respective recurrence rates were 7 (13%), 0, and 6 (5%) and the respective readmission rates were 5 (9%), 3 (12%), and 19 (9%), he said, noting that "there were no statistical differences between diagnoses for readmissions or recurrences."

Of the full study population, 64 patients (32%) received all of their antimicrobial therapy in the POIC without hospitalization, and the mean duration in the POIC was 31 days, Dr. Dailey stated. The mean therapy durations by infection type were 20, 31, and 37 days for bacteremia, endocarditis, and osteomyelitis patients, respectively, he said.

Analysis of the safety outcomes showed that 53 patients (26%) had a total of 74 adverse events related to intravenous antibiotic treatment, including five serious adverse events that required either hospitalization or additional intervention, according to Dr. Dailey. Four patients had catheter-related infections, and three had catheter device failures that required removal or replacement, he said. Of the 19 readmissions, 4 each were due to adverse drug reactions and device failure, 3 were related to disease exacerbation, and 8 were for other medical complications, he said.

"Our results are more favorable than some of the other studies that have been reported over the past few years," Dr. Dailey stated, referring specifically to a collection of studies in which the treatment of patients with Staphylococcus aureus bacteremia with or without infective endocarditis was reported to be 86% compared with the 88% and 93% observed, respectively, in the endocarditis and bacteremic patients in the current investigation (J. Antimicrob. Chemother. 2009;63:1034-42).

The results suggest that the treatment of bacteremia, infective endocarditis, and osteomyelitis is safe and effective in the POIC setting, according to Dr. Dailey. "The recurrence and remission rates appear to be low in the outpatient setting as well," he said, acknowledging, however, that the study is limited by its size and its retrospective design. "Further investigation is warranted," he noted.

Dr. Dailey disclosed a financial relationship with Healix Infusion Therapy.

BOSTON – Serious infections requiring long-term treatment can be managed safely and effectively with outpatient parenteral antimicrobial therapy administered by infusion centers, a study has shown.

In an observational review of data from multiple infectious disease physician office infusion centers (POICs) over a 6-month period, the recurrence and readmission rates for patients treated for bacteremia, endocarditis, and osteomyelitis were low and more favorable than previously observed in similar studies, Dr. Michael P. Dailey reported at the annual meeting of the Infectious Diseases Society of America.

Of 203 patients (mean age 59 years) treated for bacteremia (54), infective endocarditis (26), and osteomyelitis (123) from Jan. 1, 2010, to June 30, 2010, 188 (93%) met the study criteria for clinical success, defined as cured or improved, while 13 (6%) and 19 (9%), respectively, experienced a recurrence within 6 months or required readmission during therapy, said Dr. Dailey of an infectious disease specialist in Roswell, Ga.

By infection type, 50 (93%) of the bacteremia patients, 23 (88%) of the endocarditis patients, and 115 (93%) of the osteomyelitis patients achieved clinical success, while the respective recurrence rates were 7 (13%), 0, and 6 (5%) and the respective readmission rates were 5 (9%), 3 (12%), and 19 (9%), he said, noting that "there were no statistical differences between diagnoses for readmissions or recurrences."

Of the full study population, 64 patients (32%) received all of their antimicrobial therapy in the POIC without hospitalization, and the mean duration in the POIC was 31 days, Dr. Dailey stated. The mean therapy durations by infection type were 20, 31, and 37 days for bacteremia, endocarditis, and osteomyelitis patients, respectively, he said.

Analysis of the safety outcomes showed that 53 patients (26%) had a total of 74 adverse events related to intravenous antibiotic treatment, including five serious adverse events that required either hospitalization or additional intervention, according to Dr. Dailey. Four patients had catheter-related infections, and three had catheter device failures that required removal or replacement, he said. Of the 19 readmissions, 4 each were due to adverse drug reactions and device failure, 3 were related to disease exacerbation, and 8 were for other medical complications, he said.

"Our results are more favorable than some of the other studies that have been reported over the past few years," Dr. Dailey stated, referring specifically to a collection of studies in which the treatment of patients with Staphylococcus aureus bacteremia with or without infective endocarditis was reported to be 86% compared with the 88% and 93% observed, respectively, in the endocarditis and bacteremic patients in the current investigation (J. Antimicrob. Chemother. 2009;63:1034-42).

The results suggest that the treatment of bacteremia, infective endocarditis, and osteomyelitis is safe and effective in the POIC setting, according to Dr. Dailey. "The recurrence and remission rates appear to be low in the outpatient setting as well," he said, acknowledging, however, that the study is limited by its size and its retrospective design. "Further investigation is warranted," he noted.

Dr. Dailey disclosed a financial relationship with Healix Infusion Therapy.

BOSTON – Serious infections requiring long-term treatment can be managed safely and effectively with outpatient parenteral antimicrobial therapy administered by infusion centers, a study has shown.

In an observational review of data from multiple infectious disease physician office infusion centers (POICs) over a 6-month period, the recurrence and readmission rates for patients treated for bacteremia, endocarditis, and osteomyelitis were low and more favorable than previously observed in similar studies, Dr. Michael P. Dailey reported at the annual meeting of the Infectious Diseases Society of America.

Of 203 patients (mean age 59 years) treated for bacteremia (54), infective endocarditis (26), and osteomyelitis (123) from Jan. 1, 2010, to June 30, 2010, 188 (93%) met the study criteria for clinical success, defined as cured or improved, while 13 (6%) and 19 (9%), respectively, experienced a recurrence within 6 months or required readmission during therapy, said Dr. Dailey of an infectious disease specialist in Roswell, Ga.

By infection type, 50 (93%) of the bacteremia patients, 23 (88%) of the endocarditis patients, and 115 (93%) of the osteomyelitis patients achieved clinical success, while the respective recurrence rates were 7 (13%), 0, and 6 (5%) and the respective readmission rates were 5 (9%), 3 (12%), and 19 (9%), he said, noting that "there were no statistical differences between diagnoses for readmissions or recurrences."

Of the full study population, 64 patients (32%) received all of their antimicrobial therapy in the POIC without hospitalization, and the mean duration in the POIC was 31 days, Dr. Dailey stated. The mean therapy durations by infection type were 20, 31, and 37 days for bacteremia, endocarditis, and osteomyelitis patients, respectively, he said.

Analysis of the safety outcomes showed that 53 patients (26%) had a total of 74 adverse events related to intravenous antibiotic treatment, including five serious adverse events that required either hospitalization or additional intervention, according to Dr. Dailey. Four patients had catheter-related infections, and three had catheter device failures that required removal or replacement, he said. Of the 19 readmissions, 4 each were due to adverse drug reactions and device failure, 3 were related to disease exacerbation, and 8 were for other medical complications, he said.

"Our results are more favorable than some of the other studies that have been reported over the past few years," Dr. Dailey stated, referring specifically to a collection of studies in which the treatment of patients with Staphylococcus aureus bacteremia with or without infective endocarditis was reported to be 86% compared with the 88% and 93% observed, respectively, in the endocarditis and bacteremic patients in the current investigation (J. Antimicrob. Chemother. 2009;63:1034-42).

The results suggest that the treatment of bacteremia, infective endocarditis, and osteomyelitis is safe and effective in the POIC setting, according to Dr. Dailey. "The recurrence and remission rates appear to be low in the outpatient setting as well," he said, acknowledging, however, that the study is limited by its size and its retrospective design. "Further investigation is warranted," he noted.

Dr. Dailey disclosed a financial relationship with Healix Infusion Therapy.

BOSTON – Despite limited data on the safety and efficacy of colistin in children, the polymyxin antimicrobial has been used increasingly in high-risk pediatric patients as salvage therapy for serious infections caused by multidrug-resistant gram-negative bacteria, according to Dr. Pia S. Pannaraj.

"The escalating impact of antimicrobial selective pressure in high-risk pediatric populations has limited the therapeutic options available for the treatment of multidrug-resistant [MDR] gram-negative bacilli, which in turn has led to renewed interest in colistin, despite the known nephrotoxic and neurotoxic risks," she reported at the annual meeting of the Infectious Diseases Society of America.

In a study designed to review risk factors for acquiring multidrug-resistant gram-negative bacteria requiring colistin treatment and the adverse effects of such treatment in pediatric patients, Dr. Pannaraj of Children’s Hospital Los Angeles and colleagues reviewed their experience with colistin in pediatric patients admitted to their hospital between Jan. 1, 2005, and Oct. 31, 2010. Based on pharmacy records for that period, 53 children were treated with intravenous or nebulized colistin for treatment or suppressive therapy of an infection caused by MDR bacteria. Of the 53 children, 14 received 18 courses of the drug and were included in the analysis, she said. For comparison, the investigators chose control patients from the medical records database who had matching underlying conditions and the similar dates of birth and admission dates to the colistin patients, she said.

Multidrug resistance was defined as resistance to at least three classes of antibiotics, Dr. Pannaraj said. The underlying conditions reported in the 14 study patients included cystic fibrosis in 8, non–cystic fibrosis chronic lung disease in 3, and malignancy in 1, she said, noting that "2 of the patients were previously healthy."

"Nephrotoxicity and neurotoxicity remain a concern with colistin use in children."

The investigators performed chi-square analysis and independent and paired t-tests to compare between-group differences for dichotomous and continuous variables. According to the analysis, the children with an MDR isolate requiring colistin had more hospital days during the previous calendar year, compared with their matched controls, at 101.0 days vs. 27.2 days, respectively, Dr. Pannaraj reported. Those with MDR isolates also received more types of antibiotic than did the matched controls (6.6 vs. 4.2) for longer durations (191.0 vs. 53.8 antibiotic days), she said. The percentage of children on daily antibiotic prophylaxis was similar in the colistin and control groups, at 55.6% and 58.3%, respectively.

Four gram-negative bacteria were isolated, including 16 Pseudomonas aeruginosa, 6 Acinetobacter baumannii, 3 Klebsiella pneumoniae, and 1 Alcaligenes species, with more than one pathogen isolated in seven of the children, Dr. Pannaraj said. The indications for treatment with colistin included pulmonary exacerbation in nine patients, wound infection in four patients, and bacteremia/sepsis in four patients. The mean colistin dosage was 5.9 mg/kg per day, divided into two or three daily doses. Mean treatment duration was 13.5 days for respiratory infection, 20.8 days for wound infection, and 18.0 days for bacteremia, she reported.

Creatinine levels doubled in two children, including one who had been receiving concomitant aminoglycoside. The patient on aminoglycoside stopped both antimicrobials, while the second patient completed her course uninterrupted, Dr. Pannaraj reported. Two of the children developed neurologic symptoms, including perioral tingling at a dose of 7.6 mg/kg per day in one and headache at a dose of 5.9 mg/kg per day in another; symptoms resolved after the drug course was completed.

Of 36 control patients, 5 developed adverse events attributable to antibiotics, including neutropenia, rash, diarrhea, and vaginal itch. "The percentage of adverse events was not significantly different between colistin and control patients, at 22.2% compared with 13.9%," Dr. Pannaraj said.

The findings underscore the effect of antimicrobial selective pressure in high-risk pediatric patients and suggest that "nephrotoxicity and neurotoxicity remain a concern with colistin use in children," Dr. Pannaraj said. "We need more studies on the dosing and safety of colistin to optimize it for the treatment of high-risk children."

Dr. Pannaraj had no financial conflicts of interest to disclose.

BOSTON – Despite limited data on the safety and efficacy of colistin in children, the polymyxin antimicrobial has been used increasingly in high-risk pediatric patients as salvage therapy for serious infections caused by multidrug-resistant gram-negative bacteria, according to Dr. Pia S. Pannaraj.

"The escalating impact of antimicrobial selective pressure in high-risk pediatric populations has limited the therapeutic options available for the treatment of multidrug-resistant [MDR] gram-negative bacilli, which in turn has led to renewed interest in colistin, despite the known nephrotoxic and neurotoxic risks," she reported at the annual meeting of the Infectious Diseases Society of America.

In a study designed to review risk factors for acquiring multidrug-resistant gram-negative bacteria requiring colistin treatment and the adverse effects of such treatment in pediatric patients, Dr. Pannaraj of Children’s Hospital Los Angeles and colleagues reviewed their experience with colistin in pediatric patients admitted to their hospital between Jan. 1, 2005, and Oct. 31, 2010. Based on pharmacy records for that period, 53 children were treated with intravenous or nebulized colistin for treatment or suppressive therapy of an infection caused by MDR bacteria. Of the 53 children, 14 received 18 courses of the drug and were included in the analysis, she said. For comparison, the investigators chose control patients from the medical records database who had matching underlying conditions and the similar dates of birth and admission dates to the colistin patients, she said.

Multidrug resistance was defined as resistance to at least three classes of antibiotics, Dr. Pannaraj said. The underlying conditions reported in the 14 study patients included cystic fibrosis in 8, non–cystic fibrosis chronic lung disease in 3, and malignancy in 1, she said, noting that "2 of the patients were previously healthy."

"Nephrotoxicity and neurotoxicity remain a concern with colistin use in children."

The investigators performed chi-square analysis and independent and paired t-tests to compare between-group differences for dichotomous and continuous variables. According to the analysis, the children with an MDR isolate requiring colistin had more hospital days during the previous calendar year, compared with their matched controls, at 101.0 days vs. 27.2 days, respectively, Dr. Pannaraj reported. Those with MDR isolates also received more types of antibiotic than did the matched controls (6.6 vs. 4.2) for longer durations (191.0 vs. 53.8 antibiotic days), she said. The percentage of children on daily antibiotic prophylaxis was similar in the colistin and control groups, at 55.6% and 58.3%, respectively.

Four gram-negative bacteria were isolated, including 16 Pseudomonas aeruginosa, 6 Acinetobacter baumannii, 3 Klebsiella pneumoniae, and 1 Alcaligenes species, with more than one pathogen isolated in seven of the children, Dr. Pannaraj said. The indications for treatment with colistin included pulmonary exacerbation in nine patients, wound infection in four patients, and bacteremia/sepsis in four patients. The mean colistin dosage was 5.9 mg/kg per day, divided into two or three daily doses. Mean treatment duration was 13.5 days for respiratory infection, 20.8 days for wound infection, and 18.0 days for bacteremia, she reported.

Creatinine levels doubled in two children, including one who had been receiving concomitant aminoglycoside. The patient on aminoglycoside stopped both antimicrobials, while the second patient completed her course uninterrupted, Dr. Pannaraj reported. Two of the children developed neurologic symptoms, including perioral tingling at a dose of 7.6 mg/kg per day in one and headache at a dose of 5.9 mg/kg per day in another; symptoms resolved after the drug course was completed.

Of 36 control patients, 5 developed adverse events attributable to antibiotics, including neutropenia, rash, diarrhea, and vaginal itch. "The percentage of adverse events was not significantly different between colistin and control patients, at 22.2% compared with 13.9%," Dr. Pannaraj said.

The findings underscore the effect of antimicrobial selective pressure in high-risk pediatric patients and suggest that "nephrotoxicity and neurotoxicity remain a concern with colistin use in children," Dr. Pannaraj said. "We need more studies on the dosing and safety of colistin to optimize it for the treatment of high-risk children."

Dr. Pannaraj had no financial conflicts of interest to disclose.

BOSTON – Despite limited data on the safety and efficacy of colistin in children, the polymyxin antimicrobial has been used increasingly in high-risk pediatric patients as salvage therapy for serious infections caused by multidrug-resistant gram-negative bacteria, according to Dr. Pia S. Pannaraj.

"The escalating impact of antimicrobial selective pressure in high-risk pediatric populations has limited the therapeutic options available for the treatment of multidrug-resistant [MDR] gram-negative bacilli, which in turn has led to renewed interest in colistin, despite the known nephrotoxic and neurotoxic risks," she reported at the annual meeting of the Infectious Diseases Society of America.

In a study designed to review risk factors for acquiring multidrug-resistant gram-negative bacteria requiring colistin treatment and the adverse effects of such treatment in pediatric patients, Dr. Pannaraj of Children’s Hospital Los Angeles and colleagues reviewed their experience with colistin in pediatric patients admitted to their hospital between Jan. 1, 2005, and Oct. 31, 2010. Based on pharmacy records for that period, 53 children were treated with intravenous or nebulized colistin for treatment or suppressive therapy of an infection caused by MDR bacteria. Of the 53 children, 14 received 18 courses of the drug and were included in the analysis, she said. For comparison, the investigators chose control patients from the medical records database who had matching underlying conditions and the similar dates of birth and admission dates to the colistin patients, she said.

Multidrug resistance was defined as resistance to at least three classes of antibiotics, Dr. Pannaraj said. The underlying conditions reported in the 14 study patients included cystic fibrosis in 8, non–cystic fibrosis chronic lung disease in 3, and malignancy in 1, she said, noting that "2 of the patients were previously healthy."

"Nephrotoxicity and neurotoxicity remain a concern with colistin use in children."

The investigators performed chi-square analysis and independent and paired t-tests to compare between-group differences for dichotomous and continuous variables. According to the analysis, the children with an MDR isolate requiring colistin had more hospital days during the previous calendar year, compared with their matched controls, at 101.0 days vs. 27.2 days, respectively, Dr. Pannaraj reported. Those with MDR isolates also received more types of antibiotic than did the matched controls (6.6 vs. 4.2) for longer durations (191.0 vs. 53.8 antibiotic days), she said. The percentage of children on daily antibiotic prophylaxis was similar in the colistin and control groups, at 55.6% and 58.3%, respectively.

Four gram-negative bacteria were isolated, including 16 Pseudomonas aeruginosa, 6 Acinetobacter baumannii, 3 Klebsiella pneumoniae, and 1 Alcaligenes species, with more than one pathogen isolated in seven of the children, Dr. Pannaraj said. The indications for treatment with colistin included pulmonary exacerbation in nine patients, wound infection in four patients, and bacteremia/sepsis in four patients. The mean colistin dosage was 5.9 mg/kg per day, divided into two or three daily doses. Mean treatment duration was 13.5 days for respiratory infection, 20.8 days for wound infection, and 18.0 days for bacteremia, she reported.

Creatinine levels doubled in two children, including one who had been receiving concomitant aminoglycoside. The patient on aminoglycoside stopped both antimicrobials, while the second patient completed her course uninterrupted, Dr. Pannaraj reported. Two of the children developed neurologic symptoms, including perioral tingling at a dose of 7.6 mg/kg per day in one and headache at a dose of 5.9 mg/kg per day in another; symptoms resolved after the drug course was completed.

Of 36 control patients, 5 developed adverse events attributable to antibiotics, including neutropenia, rash, diarrhea, and vaginal itch. "The percentage of adverse events was not significantly different between colistin and control patients, at 22.2% compared with 13.9%," Dr. Pannaraj said.

The findings underscore the effect of antimicrobial selective pressure in high-risk pediatric patients and suggest that "nephrotoxicity and neurotoxicity remain a concern with colistin use in children," Dr. Pannaraj said. "We need more studies on the dosing and safety of colistin to optimize it for the treatment of high-risk children."

Dr. Pannaraj had no financial conflicts of interest to disclose.

BOSTON – Just 1% of all surgical procedures are associated with complex surgical site infections, but many develop in association with ill-suited prophylactic antibiotic regimens, according to an analysis of more than 2.4 million American who underwent cardiac or orthopedic surgery during 2006-2009.

Nevertheless, "the vast majority [of surgery patients] don’t get SSIs. Do we want to modify treatment for all patients to address the small proportion who get complex SSIs?" asked Dr. Dale W. Bratzler.

The low overall rate of complex SSIs suggests that any changes to standard SSI prophylaxis regimens should proceed cautiously. "What we need most are strategies for identifying patients at high risk for SSI due to drug-resistant organisms for targeting modified antimicrobial prophylaxis regimens," said Dr. Bratzler, a professor in the department of health administration and policy of the University of Oklahoma, Oklahoma City.

The analysis he reported at the annual meeting of the Infectious Diseases Society of America used data from two large U.S. databases collected from January 2006 to December 2009. Information on the pathogen distribution of SSIs came from the National Healthcare Safety Network database of the Centers for Disease Control and Prevention, which included data from 1,389 U.S. hospitals during this period on the number and type of SSIs that occurred in patients who underwent coronary artery bypass grafting (CABG), and those who had primary total hip or total knee replacement surgery. The second database, from the Hospital Inpatient Quality Reporting Program of the Centers for Medicare and Medicaid Services, collected data on the type of antimicrobial prophylaxis received by patients who underwent these surgical procedures at 3,330 U.S. hospitals.

"Do we want to modify treatment for all patients to address the small proportion who get complex SSIs?"

The National Healthcare Safety Network data showed that a total of 3,024 patients developed a complex SSI among the 207,053 who underwent CABG (1.5%), and 3,532 patients had a complex SSI among the 495,529 patients who had primary hip or knee replacement surgery (0.7%), Dr. Bratzler reported. Complex SSIs were defined as either deep incisional infections, or infections of an organ or surgical space. Among the CABG-associated complex SSIs, 34% were caused by gram-negative bacteria, with the balance caused by gram-positive pathogens, and 17% of all SSIs involved methicillin-resistant Staphylococcus aureus (MRSA). In the arthroplasty patients, 18% of the complex SSIs involved a gram-negative pathogen, and 21% of all infections had MRSA involvement.

The data on type of antibiotic prophylaxis used showed that among 428,541 patients who underwent CABG in this dataset, 67% received "standard" prophylaxis with either cefazolin or cefuroxime; 12% received a regimen designed for patients with beta-lactam allergy with either vancomycin or clindamycin, plus an aminoglycoside added at the provider’s discretion; and 15% had prophylaxis with an extended-spectrum regimen consisting of either vancomycin plus cefazolin or cefuroxime, or an aminoglycoside plus cefazolin or cefuroxime. The remaining 6% of patients received another prophylaxis regimen.

The prophylaxis data for 2,007,162 arthroplasty patients showed that the standard regimen was used in 77%, the beta-lactam allergy regimen in 13%, and the extended-spectrum regimen in 7%, with the remaining 3% of patients receiving something else.

Dr. Bratzler then compared the expected efficacy of the three most commonly used regimens against the pattern of SSIs that actually occurred in these patients. Patients who received the standard regimen could expect protection against about 40% of the types of bacteria that actually wound up producing SSIs. Patients who received the beta-lactam allergy regimens could expect protection against 56%-96% of the pathogens that actually caused the SSIs, and patients who received the extended-spectrum regimens could expect protection against 69%-96%, he said.

The researchers could not do a more detailed analysis of the relationship between the type of prophylaxis used and the pattern of SSIs that subsequently developed because both databases were anonymous, which precluded cross-referencing the information.

Dr. Bratzler said that he had no disclosures.

BOSTON – Just 1% of all surgical procedures are associated with complex surgical site infections, but many develop in association with ill-suited prophylactic antibiotic regimens, according to an analysis of more than 2.4 million American who underwent cardiac or orthopedic surgery during 2006-2009.

Nevertheless, "the vast majority [of surgery patients] don’t get SSIs. Do we want to modify treatment for all patients to address the small proportion who get complex SSIs?" asked Dr. Dale W. Bratzler.

The low overall rate of complex SSIs suggests that any changes to standard SSI prophylaxis regimens should proceed cautiously. "What we need most are strategies for identifying patients at high risk for SSI due to drug-resistant organisms for targeting modified antimicrobial prophylaxis regimens," said Dr. Bratzler, a professor in the department of health administration and policy of the University of Oklahoma, Oklahoma City.

The analysis he reported at the annual meeting of the Infectious Diseases Society of America used data from two large U.S. databases collected from January 2006 to December 2009. Information on the pathogen distribution of SSIs came from the National Healthcare Safety Network database of the Centers for Disease Control and Prevention, which included data from 1,389 U.S. hospitals during this period on the number and type of SSIs that occurred in patients who underwent coronary artery bypass grafting (CABG), and those who had primary total hip or total knee replacement surgery. The second database, from the Hospital Inpatient Quality Reporting Program of the Centers for Medicare and Medicaid Services, collected data on the type of antimicrobial prophylaxis received by patients who underwent these surgical procedures at 3,330 U.S. hospitals.

"Do we want to modify treatment for all patients to address the small proportion who get complex SSIs?"

The National Healthcare Safety Network data showed that a total of 3,024 patients developed a complex SSI among the 207,053 who underwent CABG (1.5%), and 3,532 patients had a complex SSI among the 495,529 patients who had primary hip or knee replacement surgery (0.7%), Dr. Bratzler reported. Complex SSIs were defined as either deep incisional infections, or infections of an organ or surgical space. Among the CABG-associated complex SSIs, 34% were caused by gram-negative bacteria, with the balance caused by gram-positive pathogens, and 17% of all SSIs involved methicillin-resistant Staphylococcus aureus (MRSA). In the arthroplasty patients, 18% of the complex SSIs involved a gram-negative pathogen, and 21% of all infections had MRSA involvement.

The data on type of antibiotic prophylaxis used showed that among 428,541 patients who underwent CABG in this dataset, 67% received "standard" prophylaxis with either cefazolin or cefuroxime; 12% received a regimen designed for patients with beta-lactam allergy with either vancomycin or clindamycin, plus an aminoglycoside added at the provider’s discretion; and 15% had prophylaxis with an extended-spectrum regimen consisting of either vancomycin plus cefazolin or cefuroxime, or an aminoglycoside plus cefazolin or cefuroxime. The remaining 6% of patients received another prophylaxis regimen.

The prophylaxis data for 2,007,162 arthroplasty patients showed that the standard regimen was used in 77%, the beta-lactam allergy regimen in 13%, and the extended-spectrum regimen in 7%, with the remaining 3% of patients receiving something else.

Dr. Bratzler then compared the expected efficacy of the three most commonly used regimens against the pattern of SSIs that actually occurred in these patients. Patients who received the standard regimen could expect protection against about 40% of the types of bacteria that actually wound up producing SSIs. Patients who received the beta-lactam allergy regimens could expect protection against 56%-96% of the pathogens that actually caused the SSIs, and patients who received the extended-spectrum regimens could expect protection against 69%-96%, he said.

The researchers could not do a more detailed analysis of the relationship between the type of prophylaxis used and the pattern of SSIs that subsequently developed because both databases were anonymous, which precluded cross-referencing the information.

Dr. Bratzler said that he had no disclosures.

BOSTON – Just 1% of all surgical procedures are associated with complex surgical site infections, but many develop in association with ill-suited prophylactic antibiotic regimens, according to an analysis of more than 2.4 million American who underwent cardiac or orthopedic surgery during 2006-2009.

Nevertheless, "the vast majority [of surgery patients] don’t get SSIs. Do we want to modify treatment for all patients to address the small proportion who get complex SSIs?" asked Dr. Dale W. Bratzler.

The low overall rate of complex SSIs suggests that any changes to standard SSI prophylaxis regimens should proceed cautiously. "What we need most are strategies for identifying patients at high risk for SSI due to drug-resistant organisms for targeting modified antimicrobial prophylaxis regimens," said Dr. Bratzler, a professor in the department of health administration and policy of the University of Oklahoma, Oklahoma City.

The analysis he reported at the annual meeting of the Infectious Diseases Society of America used data from two large U.S. databases collected from January 2006 to December 2009. Information on the pathogen distribution of SSIs came from the National Healthcare Safety Network database of the Centers for Disease Control and Prevention, which included data from 1,389 U.S. hospitals during this period on the number and type of SSIs that occurred in patients who underwent coronary artery bypass grafting (CABG), and those who had primary total hip or total knee replacement surgery. The second database, from the Hospital Inpatient Quality Reporting Program of the Centers for Medicare and Medicaid Services, collected data on the type of antimicrobial prophylaxis received by patients who underwent these surgical procedures at 3,330 U.S. hospitals.

"Do we want to modify treatment for all patients to address the small proportion who get complex SSIs?"

The National Healthcare Safety Network data showed that a total of 3,024 patients developed a complex SSI among the 207,053 who underwent CABG (1.5%), and 3,532 patients had a complex SSI among the 495,529 patients who had primary hip or knee replacement surgery (0.7%), Dr. Bratzler reported. Complex SSIs were defined as either deep incisional infections, or infections of an organ or surgical space. Among the CABG-associated complex SSIs, 34% were caused by gram-negative bacteria, with the balance caused by gram-positive pathogens, and 17% of all SSIs involved methicillin-resistant Staphylococcus aureus (MRSA). In the arthroplasty patients, 18% of the complex SSIs involved a gram-negative pathogen, and 21% of all infections had MRSA involvement.

The data on type of antibiotic prophylaxis used showed that among 428,541 patients who underwent CABG in this dataset, 67% received "standard" prophylaxis with either cefazolin or cefuroxime; 12% received a regimen designed for patients with beta-lactam allergy with either vancomycin or clindamycin, plus an aminoglycoside added at the provider’s discretion; and 15% had prophylaxis with an extended-spectrum regimen consisting of either vancomycin plus cefazolin or cefuroxime, or an aminoglycoside plus cefazolin or cefuroxime. The remaining 6% of patients received another prophylaxis regimen.

The prophylaxis data for 2,007,162 arthroplasty patients showed that the standard regimen was used in 77%, the beta-lactam allergy regimen in 13%, and the extended-spectrum regimen in 7%, with the remaining 3% of patients receiving something else.

Dr. Bratzler then compared the expected efficacy of the three most commonly used regimens against the pattern of SSIs that actually occurred in these patients. Patients who received the standard regimen could expect protection against about 40% of the types of bacteria that actually wound up producing SSIs. Patients who received the beta-lactam allergy regimens could expect protection against 56%-96% of the pathogens that actually caused the SSIs, and patients who received the extended-spectrum regimens could expect protection against 69%-96%, he said.

The researchers could not do a more detailed analysis of the relationship between the type of prophylaxis used and the pattern of SSIs that subsequently developed because both databases were anonymous, which precluded cross-referencing the information.

Dr. Bratzler said that he had no disclosures.

BOSTON – By mid-October, 2011 was already the worst year for measles cases in the U.S. since 1996.

But with 214 U.S. measles cases identified by the Centers for Disease Control and Prevention as of Oct. 14, the 2011 case number still remains very modest and allows America to remain a country where measles has been "eliminated," its status since 2000, Huong McLean, Ph.D., said at the annual meeting of the Infectious Diseases Society of America.

Photo courtesy of CDC/Dr. Heinz F. Eichenwald

For measles to be considered no longer eliminated from the United States, person-to-person transmission of the virus would need to persist in the country for a year, said Dr. McLean, an epidemiologist in the National Center for Immunization and Respiratory Diseases of the CDC in Atlanta.

"We’ve been getting a lot of imported cases, but the spread has been very limited," she said in an interview. "As long as there is measles elsewhere in the world, [the United States] is going to get importations."

The CDC attributed a third of the U.S. cases this year to direct importations, roughly similar to the 47% average importation rate each year over the past decade, she reported. Other world locations have a much greater measles burden. The CDC traced about half of the 2011 importations into the European Union, which this year has so far reported more than 28,000 measles cases, half of them in France.

The majority of U.S. measles cases this year were in children aged 19 years or younger, with 20% of the national total in infants aged 6-15 months. However, adult cases accounted for 41% of the 2011 caseload, and within that subgroup the largest number occurred in young adults aged 20-39, who had 27% of the total U.S. measles cases this year.

Among the 214 U.S. cases, 187 were in U.S. residents, and 180 cases (84%) occurred in people who had either been previously unvaccinated for measles or had an unknown vaccine status. The total also included 19 people (9%) who had previously received just one measles vaccine dose (the CDC recommends that people receive two doses to better insure immune coverage), and 15 (7%) with evidence of having received two doses, Dr. McLean said.

This year included 16 U.S. measles outbreaks, the highest number in more than a decade. The outbreaks, defined as at least three linked cases, accounted for half of the 2011 U.S. measles cases, with a median of 5.5 patients in each outbreak.

The largest U.S. 2011 outbreak as of mid-October, in the Minneapolis area, typifies a common outbreak scenario. According to a report at the meeting from the Minnesota Department of Health, an unvaccinated, U.S.-born 2-year old child traveled to Kenya. Back home in Hennepin County, Minn., the index case attended a drop-in childcare center, and a day later manifested a rash. Measles later developed in two other children at the childcare center and one household contact, and later spread to people at two homeless shelters, two health care facilities, and another childcare center. The Minnesota investigators identified 21 cases in this outbreak all together, including 16 unvaccinated people. Seven were infants too young to have been vaccinated, and nine were unvaccinated despite being of age. Seven of these nine had avoided vaccination because of safety concerns.

"Health care providers together with public health and community leaders must address growing vaccine hesitancy to ensure high immunization rates in all communities," said Pam Gahr, a senior epidemiologist with the Minnesota Department of Health, in a written statement.

Another report at the meeting addressed the public cost of a measles outbreak. Last March and April, a measles outbreak that eventually caused nine confirmed cases occurred in the Salt Lake City area. The total cost for investigating and dealing with the outbreak ran to about $330,000, or roughly $33,000 per case, reported Dr. Karyn Leniek, deputy state epidemiologist with the Utah Department of Health. Most of the expense accumulated from the salaries paid to the health care workers who worked on the outbreak.

Dwarfing the 2011 U.S. outbreaks, a Canadian outbreak occurred last May and June in a rural region of Quebec that, through early October, included 757 confirmed cases, the largest North American outbreak in more than a decade, said Philippe Bélanger, an epidemiologist with the Quebec Ministry of Health and Social Services in Montreal. Although 62% of the cases occurred in unvaccinated people, 13% of the confirmed measles cases were in people with documentation of having received two measles vaccinations, all of them 29 years old or younger, Mr. Bélanger said in a talk at the meeting.

"We need a better understanding of this outbreak, as it is unclear that the problem was only a failure to vaccinate," Mr. Bélanger said.

Dr. McLean, Ms. Gahr, Dr. Leniek, and Mr. Bélanger said they had no disclosures.

BOSTON – By mid-October, 2011 was already the worst year for measles cases in the U.S. since 1996.

But with 214 U.S. measles cases identified by the Centers for Disease Control and Prevention as of Oct. 14, the 2011 case number still remains very modest and allows America to remain a country where measles has been "eliminated," its status since 2000, Huong McLean, Ph.D., said at the annual meeting of the Infectious Diseases Society of America.

Photo courtesy of CDC/Dr. Heinz F. Eichenwald

For measles to be considered no longer eliminated from the United States, person-to-person transmission of the virus would need to persist in the country for a year, said Dr. McLean, an epidemiologist in the National Center for Immunization and Respiratory Diseases of the CDC in Atlanta.

"We’ve been getting a lot of imported cases, but the spread has been very limited," she said in an interview. "As long as there is measles elsewhere in the world, [the United States] is going to get importations."

The CDC attributed a third of the U.S. cases this year to direct importations, roughly similar to the 47% average importation rate each year over the past decade, she reported. Other world locations have a much greater measles burden. The CDC traced about half of the 2011 importations into the European Union, which this year has so far reported more than 28,000 measles cases, half of them in France.

The majority of U.S. measles cases this year were in children aged 19 years or younger, with 20% of the national total in infants aged 6-15 months. However, adult cases accounted for 41% of the 2011 caseload, and within that subgroup the largest number occurred in young adults aged 20-39, who had 27% of the total U.S. measles cases this year.

Among the 214 U.S. cases, 187 were in U.S. residents, and 180 cases (84%) occurred in people who had either been previously unvaccinated for measles or had an unknown vaccine status. The total also included 19 people (9%) who had previously received just one measles vaccine dose (the CDC recommends that people receive two doses to better insure immune coverage), and 15 (7%) with evidence of having received two doses, Dr. McLean said.

This year included 16 U.S. measles outbreaks, the highest number in more than a decade. The outbreaks, defined as at least three linked cases, accounted for half of the 2011 U.S. measles cases, with a median of 5.5 patients in each outbreak.

The largest U.S. 2011 outbreak as of mid-October, in the Minneapolis area, typifies a common outbreak scenario. According to a report at the meeting from the Minnesota Department of Health, an unvaccinated, U.S.-born 2-year old child traveled to Kenya. Back home in Hennepin County, Minn., the index case attended a drop-in childcare center, and a day later manifested a rash. Measles later developed in two other children at the childcare center and one household contact, and later spread to people at two homeless shelters, two health care facilities, and another childcare center. The Minnesota investigators identified 21 cases in this outbreak all together, including 16 unvaccinated people. Seven were infants too young to have been vaccinated, and nine were unvaccinated despite being of age. Seven of these nine had avoided vaccination because of safety concerns.

"Health care providers together with public health and community leaders must address growing vaccine hesitancy to ensure high immunization rates in all communities," said Pam Gahr, a senior epidemiologist with the Minnesota Department of Health, in a written statement.

Another report at the meeting addressed the public cost of a measles outbreak. Last March and April, a measles outbreak that eventually caused nine confirmed cases occurred in the Salt Lake City area. The total cost for investigating and dealing with the outbreak ran to about $330,000, or roughly $33,000 per case, reported Dr. Karyn Leniek, deputy state epidemiologist with the Utah Department of Health. Most of the expense accumulated from the salaries paid to the health care workers who worked on the outbreak.

Dwarfing the 2011 U.S. outbreaks, a Canadian outbreak occurred last May and June in a rural region of Quebec that, through early October, included 757 confirmed cases, the largest North American outbreak in more than a decade, said Philippe Bélanger, an epidemiologist with the Quebec Ministry of Health and Social Services in Montreal. Although 62% of the cases occurred in unvaccinated people, 13% of the confirmed measles cases were in people with documentation of having received two measles vaccinations, all of them 29 years old or younger, Mr. Bélanger said in a talk at the meeting.

"We need a better understanding of this outbreak, as it is unclear that the problem was only a failure to vaccinate," Mr. Bélanger said.

Dr. McLean, Ms. Gahr, Dr. Leniek, and Mr. Bélanger said they had no disclosures.

BOSTON – By mid-October, 2011 was already the worst year for measles cases in the U.S. since 1996.

But with 214 U.S. measles cases identified by the Centers for Disease Control and Prevention as of Oct. 14, the 2011 case number still remains very modest and allows America to remain a country where measles has been "eliminated," its status since 2000, Huong McLean, Ph.D., said at the annual meeting of the Infectious Diseases Society of America.

Photo courtesy of CDC/Dr. Heinz F. Eichenwald

For measles to be considered no longer eliminated from the United States, person-to-person transmission of the virus would need to persist in the country for a year, said Dr. McLean, an epidemiologist in the National Center for Immunization and Respiratory Diseases of the CDC in Atlanta.

"We’ve been getting a lot of imported cases, but the spread has been very limited," she said in an interview. "As long as there is measles elsewhere in the world, [the United States] is going to get importations."

The CDC attributed a third of the U.S. cases this year to direct importations, roughly similar to the 47% average importation rate each year over the past decade, she reported. Other world locations have a much greater measles burden. The CDC traced about half of the 2011 importations into the European Union, which this year has so far reported more than 28,000 measles cases, half of them in France.

The majority of U.S. measles cases this year were in children aged 19 years or younger, with 20% of the national total in infants aged 6-15 months. However, adult cases accounted for 41% of the 2011 caseload, and within that subgroup the largest number occurred in young adults aged 20-39, who had 27% of the total U.S. measles cases this year.

Among the 214 U.S. cases, 187 were in U.S. residents, and 180 cases (84%) occurred in people who had either been previously unvaccinated for measles or had an unknown vaccine status. The total also included 19 people (9%) who had previously received just one measles vaccine dose (the CDC recommends that people receive two doses to better insure immune coverage), and 15 (7%) with evidence of having received two doses, Dr. McLean said.

This year included 16 U.S. measles outbreaks, the highest number in more than a decade. The outbreaks, defined as at least three linked cases, accounted for half of the 2011 U.S. measles cases, with a median of 5.5 patients in each outbreak.

The largest U.S. 2011 outbreak as of mid-October, in the Minneapolis area, typifies a common outbreak scenario. According to a report at the meeting from the Minnesota Department of Health, an unvaccinated, U.S.-born 2-year old child traveled to Kenya. Back home in Hennepin County, Minn., the index case attended a drop-in childcare center, and a day later manifested a rash. Measles later developed in two other children at the childcare center and one household contact, and later spread to people at two homeless shelters, two health care facilities, and another childcare center. The Minnesota investigators identified 21 cases in this outbreak all together, including 16 unvaccinated people. Seven were infants too young to have been vaccinated, and nine were unvaccinated despite being of age. Seven of these nine had avoided vaccination because of safety concerns.

"Health care providers together with public health and community leaders must address growing vaccine hesitancy to ensure high immunization rates in all communities," said Pam Gahr, a senior epidemiologist with the Minnesota Department of Health, in a written statement.

Another report at the meeting addressed the public cost of a measles outbreak. Last March and April, a measles outbreak that eventually caused nine confirmed cases occurred in the Salt Lake City area. The total cost for investigating and dealing with the outbreak ran to about $330,000, or roughly $33,000 per case, reported Dr. Karyn Leniek, deputy state epidemiologist with the Utah Department of Health. Most of the expense accumulated from the salaries paid to the health care workers who worked on the outbreak.

Dwarfing the 2011 U.S. outbreaks, a Canadian outbreak occurred last May and June in a rural region of Quebec that, through early October, included 757 confirmed cases, the largest North American outbreak in more than a decade, said Philippe Bélanger, an epidemiologist with the Quebec Ministry of Health and Social Services in Montreal. Although 62% of the cases occurred in unvaccinated people, 13% of the confirmed measles cases were in people with documentation of having received two measles vaccinations, all of them 29 years old or younger, Mr. Bélanger said in a talk at the meeting.

"We need a better understanding of this outbreak, as it is unclear that the problem was only a failure to vaccinate," Mr. Bélanger said.

Dr. McLean, Ms. Gahr, Dr. Leniek, and Mr. Bélanger said they had no disclosures.

BOSTON – Mandatory assessment protocols for outpatient parenteral antimicrobial therapy appear to be scoring successes in patient selection, based on a single-center, retrospective review of cases deemed inappropriate for the treatment approach.

Appropriate denial of outpatient parenteral antimicrobial therapy (OPAT) and peripherally inserted central catheter (PICC) placement by infectious disease physicians appears to avoid unnecessary antibiotic usage, PICC-line complications, and costs without compromising successful clinical outcomes, Dr. Marjorie Conant said at the annual meeting of the Infectious Diseases Society of America (IDSA).

OPAT is being used more widely because of its potential to reduce morbidity, to allow earlier discharges, to improve quality of life, and to reduce treatment costs. But to be successful, OPAT needs to be directed at stable patients who need long-term antibiotic therapy. To assist in patient selection, IDSA practice guidelines recommend that infectious disease physicians take part in evaluating candidates for OPAT (Clin. Infect. Dis. 2004;38:1651-72), and many hospitals have implemented mandatory assessment protocols.

To date, however, "no published studies have looked at the clinical outcomes of patients who were not approved [for OPAT] or at the economic impact of averted [OPAT]," said Dr. Conant of Indiana University, Indianapolis, who performed such an analysis with coinvestigators at Wishard Health Services and Purdue University, also in Indianapolis.

The researchers reviewed the electronic medical records of patients who were considered for OPAT but were denied by the inpatient infectious disease consult service at Wishard, an inner-city, county teaching hospital. The evaluations took place from 2008 to 2010; children, pregnant women, and incarcerated individuals were not included in the study.

"No published studies have looked at the clinical outcomes of patients who were not approved [for OPAT] or at the economic impact of averted [OPAT]."

Demographic and medical data, including infection- and medication-specific information, were evaluated for each patient. Clinical outcome data at one year following the OPAT denial was used to classify cure rates. "Definitively cured" was defined as a documented clinical or microbiologic cure without recurrence of the infection for up to 1 year. "Probably cured" was presumed eradication of infection and no EMR-documented return visits for continued or worsening infection for up to 1 year. "Treatment failures" were those who experienced worsening or recurrence of the same infection.

The number of patients who experienced each of the clinical outcomes and the total number of patients in whom OPAT was averted were used to determine the overall rate of cure, probable cure, and treatment failure.

Of the 57 patients who met the study’s inclusion criteria, 32 (56%) were categorized as definitive cures, 9 (16%) were probable cures, and 16 (28%) were treatment failures, Dr. Conant reported. The cures and failures had similar rates of obesity, diabetes, and smoking. "Only age was found to be significantly different between patients who experienced clinical cure and clinical failure." Those in the cure group averaged 57 years of age; those in the failure group averaged 46 years.

Of the 16 treatment failures, "only four patients were thought to be true failures," Dr. Conant said. The remaining 12 patients either did not comply with the prescribed oral antibiotic therapy or their underlying disease processes progressed.

Thus, "4 of 57 patients in whom [OPAT] was denied by the infectious disease service experienced a true clinical failure," she said.

OPAT requires placement of a PICC line by an outside contractor, along with confirmatory chest x-ray, at a cost of approximately $1,000/patient, Dr. Conant said. Thus, the preliminary cost analysis suggests that the appropriate denial of 53 PICC lines saved the hospital approximately $53,000.

Further cost analyses are currently underway, she said, noting that when the costs of labs, antibiotics, supplies, and personnel associated with OPAT are included, "the cost savings will increase exponentially," as will the nonmonetary savings, such as reductions in mechanical PICC complications, line infections, Clostridium difficile colitis, and antibiotic resistance.

The study findings are limited by the lack of prospective monitoring of patients who were denied OPAT and the possibility that "probable cure" patients may have sought and received treatment for worsening infections that were not detected through the EMR review, Dr. Conant said.

Dr. Conant had no relevant financial conflicts to disclose.

BOSTON – Mandatory assessment protocols for outpatient parenteral antimicrobial therapy appear to be scoring successes in patient selection, based on a single-center, retrospective review of cases deemed inappropriate for the treatment approach.

Appropriate denial of outpatient parenteral antimicrobial therapy (OPAT) and peripherally inserted central catheter (PICC) placement by infectious disease physicians appears to avoid unnecessary antibiotic usage, PICC-line complications, and costs without compromising successful clinical outcomes, Dr. Marjorie Conant said at the annual meeting of the Infectious Diseases Society of America (IDSA).

OPAT is being used more widely because of its potential to reduce morbidity, to allow earlier discharges, to improve quality of life, and to reduce treatment costs. But to be successful, OPAT needs to be directed at stable patients who need long-term antibiotic therapy. To assist in patient selection, IDSA practice guidelines recommend that infectious disease physicians take part in evaluating candidates for OPAT (Clin. Infect. Dis. 2004;38:1651-72), and many hospitals have implemented mandatory assessment protocols.

To date, however, "no published studies have looked at the clinical outcomes of patients who were not approved [for OPAT] or at the economic impact of averted [OPAT]," said Dr. Conant of Indiana University, Indianapolis, who performed such an analysis with coinvestigators at Wishard Health Services and Purdue University, also in Indianapolis.

The researchers reviewed the electronic medical records of patients who were considered for OPAT but were denied by the inpatient infectious disease consult service at Wishard, an inner-city, county teaching hospital. The evaluations took place from 2008 to 2010; children, pregnant women, and incarcerated individuals were not included in the study.

"No published studies have looked at the clinical outcomes of patients who were not approved [for OPAT] or at the economic impact of averted [OPAT]."

Demographic and medical data, including infection- and medication-specific information, were evaluated for each patient. Clinical outcome data at one year following the OPAT denial was used to classify cure rates. "Definitively cured" was defined as a documented clinical or microbiologic cure without recurrence of the infection for up to 1 year. "Probably cured" was presumed eradication of infection and no EMR-documented return visits for continued or worsening infection for up to 1 year. "Treatment failures" were those who experienced worsening or recurrence of the same infection.

The number of patients who experienced each of the clinical outcomes and the total number of patients in whom OPAT was averted were used to determine the overall rate of cure, probable cure, and treatment failure.

Of the 57 patients who met the study’s inclusion criteria, 32 (56%) were categorized as definitive cures, 9 (16%) were probable cures, and 16 (28%) were treatment failures, Dr. Conant reported. The cures and failures had similar rates of obesity, diabetes, and smoking. "Only age was found to be significantly different between patients who experienced clinical cure and clinical failure." Those in the cure group averaged 57 years of age; those in the failure group averaged 46 years.

Of the 16 treatment failures, "only four patients were thought to be true failures," Dr. Conant said. The remaining 12 patients either did not comply with the prescribed oral antibiotic therapy or their underlying disease processes progressed.

Thus, "4 of 57 patients in whom [OPAT] was denied by the infectious disease service experienced a true clinical failure," she said.

OPAT requires placement of a PICC line by an outside contractor, along with confirmatory chest x-ray, at a cost of approximately $1,000/patient, Dr. Conant said. Thus, the preliminary cost analysis suggests that the appropriate denial of 53 PICC lines saved the hospital approximately $53,000.

Further cost analyses are currently underway, she said, noting that when the costs of labs, antibiotics, supplies, and personnel associated with OPAT are included, "the cost savings will increase exponentially," as will the nonmonetary savings, such as reductions in mechanical PICC complications, line infections, Clostridium difficile colitis, and antibiotic resistance.

The study findings are limited by the lack of prospective monitoring of patients who were denied OPAT and the possibility that "probable cure" patients may have sought and received treatment for worsening infections that were not detected through the EMR review, Dr. Conant said.

Dr. Conant had no relevant financial conflicts to disclose.

BOSTON – Mandatory assessment protocols for outpatient parenteral antimicrobial therapy appear to be scoring successes in patient selection, based on a single-center, retrospective review of cases deemed inappropriate for the treatment approach.

Appropriate denial of outpatient parenteral antimicrobial therapy (OPAT) and peripherally inserted central catheter (PICC) placement by infectious disease physicians appears to avoid unnecessary antibiotic usage, PICC-line complications, and costs without compromising successful clinical outcomes, Dr. Marjorie Conant said at the annual meeting of the Infectious Diseases Society of America (IDSA).

OPAT is being used more widely because of its potential to reduce morbidity, to allow earlier discharges, to improve quality of life, and to reduce treatment costs. But to be successful, OPAT needs to be directed at stable patients who need long-term antibiotic therapy. To assist in patient selection, IDSA practice guidelines recommend that infectious disease physicians take part in evaluating candidates for OPAT (Clin. Infect. Dis. 2004;38:1651-72), and many hospitals have implemented mandatory assessment protocols.

To date, however, "no published studies have looked at the clinical outcomes of patients who were not approved [for OPAT] or at the economic impact of averted [OPAT]," said Dr. Conant of Indiana University, Indianapolis, who performed such an analysis with coinvestigators at Wishard Health Services and Purdue University, also in Indianapolis.

The researchers reviewed the electronic medical records of patients who were considered for OPAT but were denied by the inpatient infectious disease consult service at Wishard, an inner-city, county teaching hospital. The evaluations took place from 2008 to 2010; children, pregnant women, and incarcerated individuals were not included in the study.

"No published studies have looked at the clinical outcomes of patients who were not approved [for OPAT] or at the economic impact of averted [OPAT]."

Demographic and medical data, including infection- and medication-specific information, were evaluated for each patient. Clinical outcome data at one year following the OPAT denial was used to classify cure rates. "Definitively cured" was defined as a documented clinical or microbiologic cure without recurrence of the infection for up to 1 year. "Probably cured" was presumed eradication of infection and no EMR-documented return visits for continued or worsening infection for up to 1 year. "Treatment failures" were those who experienced worsening or recurrence of the same infection.

The number of patients who experienced each of the clinical outcomes and the total number of patients in whom OPAT was averted were used to determine the overall rate of cure, probable cure, and treatment failure.

Of the 57 patients who met the study’s inclusion criteria, 32 (56%) were categorized as definitive cures, 9 (16%) were probable cures, and 16 (28%) were treatment failures, Dr. Conant reported. The cures and failures had similar rates of obesity, diabetes, and smoking. "Only age was found to be significantly different between patients who experienced clinical cure and clinical failure." Those in the cure group averaged 57 years of age; those in the failure group averaged 46 years.

Of the 16 treatment failures, "only four patients were thought to be true failures," Dr. Conant said. The remaining 12 patients either did not comply with the prescribed oral antibiotic therapy or their underlying disease processes progressed.

Thus, "4 of 57 patients in whom [OPAT] was denied by the infectious disease service experienced a true clinical failure," she said.

OPAT requires placement of a PICC line by an outside contractor, along with confirmatory chest x-ray, at a cost of approximately $1,000/patient, Dr. Conant said. Thus, the preliminary cost analysis suggests that the appropriate denial of 53 PICC lines saved the hospital approximately $53,000.

Further cost analyses are currently underway, she said, noting that when the costs of labs, antibiotics, supplies, and personnel associated with OPAT are included, "the cost savings will increase exponentially," as will the nonmonetary savings, such as reductions in mechanical PICC complications, line infections, Clostridium difficile colitis, and antibiotic resistance.

The study findings are limited by the lack of prospective monitoring of patients who were denied OPAT and the possibility that "probable cure" patients may have sought and received treatment for worsening infections that were not detected through the EMR review, Dr. Conant said.

Dr. Conant had no relevant financial conflicts to disclose.

BOSTON – Daily bathing of pediatric patients in the intensive care unit with a chlorhexidine gluconate–containing cloth led to a statistically significant 35% reduction in the incidence of bloodstream infections in a randomized, controlled, 1-year study of more than 4,000 patients at five U.S. centers.

The results also showed a consistent 28% drop in the incidence of central line–associated bloodstream infections (CLABSI) with daily chlorhexidine gluconate baths in the pediatric ICU patients studied, although the overall rate of CLABSI was low and hence this difference was not statistically significant, Dr. Aaron M. Milstone said at the annual meeting of the Infectious Diseases Society of America.

"We showed that children on this treatment had a significant reduction in bacteremias. This is dramatic, and we’re pretty excited. In our ICU we’ve agreed that the bacteremia effect is relevant and worth targeting. We have started discussions about using this [routinely] in our population," as have several of the other ICUs that participated in the study, said Dr. Milstone, a pediatric infectious diseases physician at Johns Hopkins Medical Center in Baltimore.

"When a child has a positive blood culture in the ICU, they undergo further blood culturing, they receive antibiotics for 48 hours or longer, and they remain in the ICU longer, so there are costs from these bacteremias, even if they are only contaminated blood cultures," he said in an interview. In other cases, the bloodstream infections themselves could be clinically significant and result in increased morbidity and mortality.

Additional findings from the study reported last April showed that the daily baths were safe and well tolerated, and did not produce significant adverse effects, Dr. Milstone noted.

Although the study specifically used a marketed cloth that is impregnated with 2% chlorhexidine gluconate as the delivery vehicle for the antiseptic, "I think that any chlorhexidine product may be equally effective," he said in an interview. "We used this cloth because it was convenient and easy to apply, but I think what made the difference was reducing bacteria on the [patients’] skin."

The Pediatric Scrubbing with Chlorhexidine Reduces Unwanted Bacteria (SCRUB) study ran in 10 pediatric ICUs at five U.S. medical centers. The study enrolled patients aged 2 months or older who had been in the ICU for more than 2 days. The average age of the enrolled patients varied among the ICUs, from less than 1 year at some sites to 7 years at others sites. Children were excluded from the study if they had a chlorhexidine allergy, lumbar or epidural drains, severe skin disease, or burns.

Randomization occurred among the 10 pediatric ICUs that participated. During the first 6 months of the study, five of the units routinely bathed all of the enrolled patients with chlorhexidine, and the other five used daily baths with soap and water only or with a washcloth with no added soap. After a 2-week hiatus, the ICUs switched to the other bathing method.

"We showed that children on this treatment had a significant reduction in bacteremias."

The study included 2,525 children in the control arm and 1,547 in the chlorhexidine arm in a "modified" intention-to-treat analysis. An additional 875 children initially randomized to the chlorhexidine arm never received any treatment because the researchers did not receive consent from a parent or guardian. The 1,547 children in the chlorhexidine arm included 71 patients for whom consent existed but who withdrew or were excluded.

During the study, patients had a total of 115 bloodstream infections, including 42 with CLABSI. The researchers saw a reduced number of bacteremias among the chlorhexidine-treated children at 8 of the 10 participating ICUs, showing "a consistent and robust" treatment effect, Dr. Milstone said.

The chlorhexidine treatment worked most effectively at reducing gram-positive bloodstream infections, which dropped by 46% compared with the control group, a significant difference. The researchers isolated gram-positive bacteria from 77 of the 115 (67%) bacteremic specimens.

The study was partially funded by Sage Products, which markets the chlorhexidine-impregnated cloth used in the study. Dr. Milstone said that he has no personal financial disclosures.

BOSTON – Daily bathing of pediatric patients in the intensive care unit with a chlorhexidine gluconate–containing cloth led to a statistically significant 35% reduction in the incidence of bloodstream infections in a randomized, controlled, 1-year study of more than 4,000 patients at five U.S. centers.

The results also showed a consistent 28% drop in the incidence of central line–associated bloodstream infections (CLABSI) with daily chlorhexidine gluconate baths in the pediatric ICU patients studied, although the overall rate of CLABSI was low and hence this difference was not statistically significant, Dr. Aaron M. Milstone said at the annual meeting of the Infectious Diseases Society of America.

"We showed that children on this treatment had a significant reduction in bacteremias. This is dramatic, and we’re pretty excited. In our ICU we’ve agreed that the bacteremia effect is relevant and worth targeting. We have started discussions about using this [routinely] in our population," as have several of the other ICUs that participated in the study, said Dr. Milstone, a pediatric infectious diseases physician at Johns Hopkins Medical Center in Baltimore.

"When a child has a positive blood culture in the ICU, they undergo further blood culturing, they receive antibiotics for 48 hours or longer, and they remain in the ICU longer, so there are costs from these bacteremias, even if they are only contaminated blood cultures," he said in an interview. In other cases, the bloodstream infections themselves could be clinically significant and result in increased morbidity and mortality.

Additional findings from the study reported last April showed that the daily baths were safe and well tolerated, and did not produce significant adverse effects, Dr. Milstone noted.

Although the study specifically used a marketed cloth that is impregnated with 2% chlorhexidine gluconate as the delivery vehicle for the antiseptic, "I think that any chlorhexidine product may be equally effective," he said in an interview. "We used this cloth because it was convenient and easy to apply, but I think what made the difference was reducing bacteria on the [patients’] skin."

The Pediatric Scrubbing with Chlorhexidine Reduces Unwanted Bacteria (SCRUB) study ran in 10 pediatric ICUs at five U.S. medical centers. The study enrolled patients aged 2 months or older who had been in the ICU for more than 2 days. The average age of the enrolled patients varied among the ICUs, from less than 1 year at some sites to 7 years at others sites. Children were excluded from the study if they had a chlorhexidine allergy, lumbar or epidural drains, severe skin disease, or burns.

Randomization occurred among the 10 pediatric ICUs that participated. During the first 6 months of the study, five of the units routinely bathed all of the enrolled patients with chlorhexidine, and the other five used daily baths with soap and water only or with a washcloth with no added soap. After a 2-week hiatus, the ICUs switched to the other bathing method.

"We showed that children on this treatment had a significant reduction in bacteremias."

The study included 2,525 children in the control arm and 1,547 in the chlorhexidine arm in a "modified" intention-to-treat analysis. An additional 875 children initially randomized to the chlorhexidine arm never received any treatment because the researchers did not receive consent from a parent or guardian. The 1,547 children in the chlorhexidine arm included 71 patients for whom consent existed but who withdrew or were excluded.

During the study, patients had a total of 115 bloodstream infections, including 42 with CLABSI. The researchers saw a reduced number of bacteremias among the chlorhexidine-treated children at 8 of the 10 participating ICUs, showing "a consistent and robust" treatment effect, Dr. Milstone said.

The chlorhexidine treatment worked most effectively at reducing gram-positive bloodstream infections, which dropped by 46% compared with the control group, a significant difference. The researchers isolated gram-positive bacteria from 77 of the 115 (67%) bacteremic specimens.

The study was partially funded by Sage Products, which markets the chlorhexidine-impregnated cloth used in the study. Dr. Milstone said that he has no personal financial disclosures.

BOSTON – Daily bathing of pediatric patients in the intensive care unit with a chlorhexidine gluconate–containing cloth led to a statistically significant 35% reduction in the incidence of bloodstream infections in a randomized, controlled, 1-year study of more than 4,000 patients at five U.S. centers.

The results also showed a consistent 28% drop in the incidence of central line–associated bloodstream infections (CLABSI) with daily chlorhexidine gluconate baths in the pediatric ICU patients studied, although the overall rate of CLABSI was low and hence this difference was not statistically significant, Dr. Aaron M. Milstone said at the annual meeting of the Infectious Diseases Society of America.

"We showed that children on this treatment had a significant reduction in bacteremias. This is dramatic, and we’re pretty excited. In our ICU we’ve agreed that the bacteremia effect is relevant and worth targeting. We have started discussions about using this [routinely] in our population," as have several of the other ICUs that participated in the study, said Dr. Milstone, a pediatric infectious diseases physician at Johns Hopkins Medical Center in Baltimore.

"When a child has a positive blood culture in the ICU, they undergo further blood culturing, they receive antibiotics for 48 hours or longer, and they remain in the ICU longer, so there are costs from these bacteremias, even if they are only contaminated blood cultures," he said in an interview. In other cases, the bloodstream infections themselves could be clinically significant and result in increased morbidity and mortality.

Additional findings from the study reported last April showed that the daily baths were safe and well tolerated, and did not produce significant adverse effects, Dr. Milstone noted.

Although the study specifically used a marketed cloth that is impregnated with 2% chlorhexidine gluconate as the delivery vehicle for the antiseptic, "I think that any chlorhexidine product may be equally effective," he said in an interview. "We used this cloth because it was convenient and easy to apply, but I think what made the difference was reducing bacteria on the [patients’] skin."

The Pediatric Scrubbing with Chlorhexidine Reduces Unwanted Bacteria (SCRUB) study ran in 10 pediatric ICUs at five U.S. medical centers. The study enrolled patients aged 2 months or older who had been in the ICU for more than 2 days. The average age of the enrolled patients varied among the ICUs, from less than 1 year at some sites to 7 years at others sites. Children were excluded from the study if they had a chlorhexidine allergy, lumbar or epidural drains, severe skin disease, or burns.

Randomization occurred among the 10 pediatric ICUs that participated. During the first 6 months of the study, five of the units routinely bathed all of the enrolled patients with chlorhexidine, and the other five used daily baths with soap and water only or with a washcloth with no added soap. After a 2-week hiatus, the ICUs switched to the other bathing method.

"We showed that children on this treatment had a significant reduction in bacteremias."

The study included 2,525 children in the control arm and 1,547 in the chlorhexidine arm in a "modified" intention-to-treat analysis. An additional 875 children initially randomized to the chlorhexidine arm never received any treatment because the researchers did not receive consent from a parent or guardian. The 1,547 children in the chlorhexidine arm included 71 patients for whom consent existed but who withdrew or were excluded.

During the study, patients had a total of 115 bloodstream infections, including 42 with CLABSI. The researchers saw a reduced number of bacteremias among the chlorhexidine-treated children at 8 of the 10 participating ICUs, showing "a consistent and robust" treatment effect, Dr. Milstone said.

The chlorhexidine treatment worked most effectively at reducing gram-positive bloodstream infections, which dropped by 46% compared with the control group, a significant difference. The researchers isolated gram-positive bacteria from 77 of the 115 (67%) bacteremic specimens.

The study was partially funded by Sage Products, which markets the chlorhexidine-impregnated cloth used in the study. Dr. Milstone said that he has no personal financial disclosures.