Miriam E. Tucker

ATLANTA — Severe combined immune deficiency is a contraindication to receipt of the rotavirus vaccine.

On Dec. 23, 2009, the Food and Drug Administration approved a request from Merck & Co. to add severe combined immune deficiency (SCID) as a contraindication to the RotaTeq product label. After that, the Centers for Disease Control and Prevention recommended that the contraindication apply to both Rotateq and the other licensed rotavirus vaccine, GlaxoSmithKline's Rotarix, Dr. Catherine Yen of the CDC's division of viral diseases said at the winter meeting of the CDC's Advisory Committee on Immunization Practices.

In March 2009, the CDC received reports of two infants diagnosed with SCID who had infection with the pentavalent rotavirus vaccine (RV5, Rotateq). Since then, an additional four cases have been reported in the United States, and there was one published case from Australia. The seven confirmed cases—three males and four females—ranged in age from less than 1 week to 11 months.

All had one or more coinfections, including five patients with the opportunistic fungal agent Pneumocystis jirovecci, one with salmonella, and one with Escherichia coli.

Five patients were treated by bone marrow transplant, and the other two were awaiting transplant at the time of the data review, Dr. Yen said.

The CDC will continue to monitor reports of rotavirus vaccine infection in infants with SCID.

In related news, the CDC's Advisory Committee for Heritable Disorders in Newborns and Children recommended on Jan. 21, 2010, adding SCID to the core panel for uniform newborn screening. The recommendation is currently awaiting approval by the Department of Health and Human Services.

Disclosures: None reported.

ATLANTA — Severe combined immune deficiency is a contraindication to receipt of the rotavirus vaccine.

On Dec. 23, 2009, the Food and Drug Administration approved a request from Merck & Co. to add severe combined immune deficiency (SCID) as a contraindication to the RotaTeq product label. After that, the Centers for Disease Control and Prevention recommended that the contraindication apply to both Rotateq and the other licensed rotavirus vaccine, GlaxoSmithKline's Rotarix, Dr. Catherine Yen of the CDC's division of viral diseases said at the winter meeting of the CDC's Advisory Committee on Immunization Practices.

In March 2009, the CDC received reports of two infants diagnosed with SCID who had infection with the pentavalent rotavirus vaccine (RV5, Rotateq). Since then, an additional four cases have been reported in the United States, and there was one published case from Australia. The seven confirmed cases—three males and four females—ranged in age from less than 1 week to 11 months.

All had one or more coinfections, including five patients with the opportunistic fungal agent Pneumocystis jirovecci, one with salmonella, and one with Escherichia coli.

Five patients were treated by bone marrow transplant, and the other two were awaiting transplant at the time of the data review, Dr. Yen said.

The CDC will continue to monitor reports of rotavirus vaccine infection in infants with SCID.

In related news, the CDC's Advisory Committee for Heritable Disorders in Newborns and Children recommended on Jan. 21, 2010, adding SCID to the core panel for uniform newborn screening. The recommendation is currently awaiting approval by the Department of Health and Human Services.

Disclosures: None reported.

ATLANTA — Severe combined immune deficiency is a contraindication to receipt of the rotavirus vaccine.

On Dec. 23, 2009, the Food and Drug Administration approved a request from Merck & Co. to add severe combined immune deficiency (SCID) as a contraindication to the RotaTeq product label. After that, the Centers for Disease Control and Prevention recommended that the contraindication apply to both Rotateq and the other licensed rotavirus vaccine, GlaxoSmithKline's Rotarix, Dr. Catherine Yen of the CDC's division of viral diseases said at the winter meeting of the CDC's Advisory Committee on Immunization Practices.

In March 2009, the CDC received reports of two infants diagnosed with SCID who had infection with the pentavalent rotavirus vaccine (RV5, Rotateq). Since then, an additional four cases have been reported in the United States, and there was one published case from Australia. The seven confirmed cases—three males and four females—ranged in age from less than 1 week to 11 months.

All had one or more coinfections, including five patients with the opportunistic fungal agent Pneumocystis jirovecci, one with salmonella, and one with Escherichia coli.

Five patients were treated by bone marrow transplant, and the other two were awaiting transplant at the time of the data review, Dr. Yen said.

The CDC will continue to monitor reports of rotavirus vaccine infection in infants with SCID.

In related news, the CDC's Advisory Committee for Heritable Disorders in Newborns and Children recommended on Jan. 21, 2010, adding SCID to the core panel for uniform newborn screening. The recommendation is currently awaiting approval by the Department of Health and Human Services.

Disclosures: None reported.

ATLANTA — The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention voted for universal immunization against influenza, starting with the 2010-2011 season.

Specifically, the committee voted to recommend influenza immunization for healthy people aged 19-49 years, the only group aged 6 months and older that had not been targeted in previous recommendations.

The committee had considered universal influenza immunization in previous years but had stopped short of endorsing it, said Dr. Anthony Fiore of the CDC's National Center for Immunization and Respiratory Diseases, Atlanta.

The 2009 pandemic influenza changed the picture.

About 90% of hospitalizations and deaths occurred in individuals younger than 65 years, many of them adults aged 19-49 years.

Moreover, adults aged 19-24 years had been among the targeted priority groups for the 2009-2010 monovalent H1N1 vaccine, he said.

It's likely that 2009 pandemic A(H1N1)–like viruses will continue circulating in 2010-2011, and the proportion of healthy adults now immune is unknown, Dr. Fiore noted.

Another consideration: Obesity, which affects 28% of U.S. adults, was identified as a new independent risk factor for severe illness with the pandemic A(H1N1) strain.

Recommendations of ACIP become recommendations of the CDC once they are accepted by the director of the CDC and the Secretary of Health and Human Services and are published in the CDC's Morbidity and Mortality Weekly Report.

The committee had considered universal flu immunization previously, but had stopped short of endorsing it.

Source DR. FIORE

ATLANTA — The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention voted for universal immunization against influenza, starting with the 2010-2011 season.

Specifically, the committee voted to recommend influenza immunization for healthy people aged 19-49 years, the only group aged 6 months and older that had not been targeted in previous recommendations.

The committee had considered universal influenza immunization in previous years but had stopped short of endorsing it, said Dr. Anthony Fiore of the CDC's National Center for Immunization and Respiratory Diseases, Atlanta.

The 2009 pandemic influenza changed the picture.

About 90% of hospitalizations and deaths occurred in individuals younger than 65 years, many of them adults aged 19-49 years.

Moreover, adults aged 19-24 years had been among the targeted priority groups for the 2009-2010 monovalent H1N1 vaccine, he said.

It's likely that 2009 pandemic A(H1N1)–like viruses will continue circulating in 2010-2011, and the proportion of healthy adults now immune is unknown, Dr. Fiore noted.

Another consideration: Obesity, which affects 28% of U.S. adults, was identified as a new independent risk factor for severe illness with the pandemic A(H1N1) strain.

Recommendations of ACIP become recommendations of the CDC once they are accepted by the director of the CDC and the Secretary of Health and Human Services and are published in the CDC's Morbidity and Mortality Weekly Report.

The committee had considered universal flu immunization previously, but had stopped short of endorsing it.

Source DR. FIORE

ATLANTA — The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention voted for universal immunization against influenza, starting with the 2010-2011 season.

Specifically, the committee voted to recommend influenza immunization for healthy people aged 19-49 years, the only group aged 6 months and older that had not been targeted in previous recommendations.

The committee had considered universal influenza immunization in previous years but had stopped short of endorsing it, said Dr. Anthony Fiore of the CDC's National Center for Immunization and Respiratory Diseases, Atlanta.

The 2009 pandemic influenza changed the picture.

About 90% of hospitalizations and deaths occurred in individuals younger than 65 years, many of them adults aged 19-49 years.

Moreover, adults aged 19-24 years had been among the targeted priority groups for the 2009-2010 monovalent H1N1 vaccine, he said.

It's likely that 2009 pandemic A(H1N1)–like viruses will continue circulating in 2010-2011, and the proportion of healthy adults now immune is unknown, Dr. Fiore noted.

Another consideration: Obesity, which affects 28% of U.S. adults, was identified as a new independent risk factor for severe illness with the pandemic A(H1N1) strain.

Recommendations of ACIP become recommendations of the CDC once they are accepted by the director of the CDC and the Secretary of Health and Human Services and are published in the CDC's Morbidity and Mortality Weekly Report.

The committee had considered universal flu immunization previously, but had stopped short of endorsing it.

Source DR. FIORE

BETHESDA, MD. — Invasive infections in children caused by community-acquired methicillin-resistant Staphylococcus aureus are on the rise.

Though still far less common than simple skin and soft tissue CA-MRSA infections, increasing reports of serious infections such as osteomyelitis, bacteremia, and pneumonia have been raising concern in recent years. The increase appears to be related at least in part to the emergence of the “USA300” S. aureus clone containing the Panton-Valentine leukocidin (PVL) genes, Dr. Sheldon L. Kaplan said at the annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.

Rates of severe infection have been rising as MRSA has become more common in the community. Recommendations from the American Academy of Pediatrics state that in areas where MRSA accounts for 10% or more of CA-MRSA isolates, initial empiric therapy of severe infections that could be due to S. aureus should include vancomycin. Naficillin should also be included because it's superior to vancomycin for treating methicillin-sensitive S. aureus (MSSA).

Use of clindamycin should be based on local susceptibility. “You need to know the clindamycin susceptibility of CA-MRSA isolates in your area,” said Dr. Kaplan, head of the pediatric infectious disease section at Baylor College of Medicine and chief of the infectious disease service at Texas Children's Hospital, both in Houston.

At Le Bonheur Children's Medical Center in Memphis, the rate of acute osteoarticular infections increased from 2.6 to 6.0 per 1,000 admissions between 2000 and 2004. While the proportion of those infections caused by MSSA remained constant at 10%–13%, those caused by MRSA rose from 4% to 40%. Moreover, 71% of the patients with MRSA had subperiosteal abscesses, compared with 38% of those with MSSA, and surgical procedures were required in 91% with MRSA versus 62% with MSSA (J. Pediatr. Orthop. 2006;26:701-2). Similar findings have been reported elsewhere, Dr. Kaplan noted.

Recent studies have shown that osteomyelitis caused by PVL-positive S. aureus strains was associated with more severe local disease and a greater systemic inflammatory response, compared with osteomyelitis caused by S. aureus not containing that gene (Pediatrics 2006;117:433-40), and that PVL-positive isolates were associated with an increased likelihood of complications in children with osteomyelitis (Pediatr. Infect. Dis. J. 2005;24:284-5).

MRI appears to be the optimal method for detection of osteomyelitis resulting from community-acquired S. aureus.

In a retrospective study by Dr. Kaplan and his associates of 199 such children seen between August 2001 and December 2006, MRI had a sensitivity of 98% for diagnosing the infection, compared with a 53% sensitivity with bone scintigraphy. Of 36 patients who had both imaging studies done, results were discordant in 17 cases. In all of those, the MRI diagnosis proved to be the correct one (Pediatr. Radiol. 2008;38:841-7).

The study also showed that MRI—but not bone scan—allowed for visualization of extraosseous complications, including subperiosteal abscesses in 77 patients, pyomyositis in 43, septic arthritis in 31, and deep vein thrombosis in 12. “Clearly, MRI was superior to bone scan in detecting bone infection. In our institution, MRI is the first thing we use. It can help pick up other areas of concern,” Dr. Kaplan noted.

Some of these extraosseous complications also appear to be on the rise. At least two recent reports have documented cases of venous thrombophlebitis among children with invasive S. aureus infections. At Children's Medical Center in Dallas, 10 of 35 children with confirmed osteomyelitis developed deep vein thrombosis during the acute infection, with evidence of dissemination in 6 (J. Pediatr. 2006;149:537-41).

And at Texas Children's, Dr. Kaplan and his associates reported on nine children seen between 1999 and 2004 who had venous thrombosis adjacent to the site of staphylococcal osteomyelitis. Seven patients had community-acquired infections caused by MRSA belonging to the same USA300 clonal group, and all seven carried PVL genes. The USA300 clone may “have a unique propensity to cause [venous thrombosis] in association with osteomyelitis,” they wrote (Pediatrics 2006;117:1673-9).

Since then, they've seen about 40-50 children with osteomyelitis who developed thrombosis, despite not having genetic prothrombotic conditions. “We don't understand what's going on. There's clearly something different about these community isolates, especially the USA300 strain,” Dr. Kaplan commented.

The USA300 MRSA genotype has also been implicated in septic arthritis. Among 44 isolates taken from 45 patients at Texas Children's with septic arthritis caused by S. aureus, 16 were MRSA; of these, 13 were USA300 and 14 were PVL-positive. Infections caused by USA300 were more likely to be associated with a longer duration of fever, bacteremia, and a C-reactive protein level of 10 mg/dL or greater (Pediatr. Infect. Dis. J. 2009;28:1076-80).

Rates of pyomyositis and myositis also have been on the rise at Texas Children's, and can be correlated to the emergence of CA-MRSA. Among 45 previously healthy children with bacterial pyomyositis or myositis, the cause was S. aureus in 58%. Of 24 community-acquired S. aureus isolates that were available, 15 were MRSA and 9 were MSSA. A total of 16 (including all the MRSA) isolates were found to be USA300, and 17 carried the PVL genes. The presence of MRSA, USA300, and/or the PVL genes was associated with a greater requirement for drainage procedures (Clin. Infect. Dis. 2006;43:953-60).

“Infection of muscles is something we just never saw in the past,” Dr. Kaplan commented.

Pulmonary manifestations are another increasingly common complication of CA-MRSA. An investigation of 70 children with invasive staphylococcal infections at Texas Children's between 2001 and 2004 showed that 47 had MRSA. Compared with 10 who had MSSA, those with MRSA were more likely to have pneumonia, empyema, lung abscess, and atelectasis. The presence of PVL was associated with abnormal chest image findings in patients with secondary pneumonia (Clin. Infect. Dis. 2005;41:583-90).

Influenza complicated by staph infections is also becoming more common, with most of these cases attributable to MRSA. A study by the Centers for Disease Control and Prevention comparing pediatric deaths during three influenza seasons revealed that bacterial coinfection increased substantially, from 6% in 2004-2005 to 15% in 2005-2006 to 34% in 2006-2007. Isolation of S. aureus from a sterile site rose from just 1 case in 2004-2005 to 22 in 2006-2007, of which two-thirds were MRSA.

Disclosures: Dr. Kaplan has received research grants from Pfizer and Cubist Pharmaceuticals.

'Infection of muscles is something we just never saw in the past.'

Source DR. KAPLAN

An axial view of proximal left tibial osteomyelitis with subperiosteal abscess and extraosseous soft tissue inflammation is shown (top). A sagittal view is also shown (bottom).

Source Images courtesy Dr. Sheldon L. Kaplan

BETHESDA, MD. — Invasive infections in children caused by community-acquired methicillin-resistant Staphylococcus aureus are on the rise.

Though still far less common than simple skin and soft tissue CA-MRSA infections, increasing reports of serious infections such as osteomyelitis, bacteremia, and pneumonia have been raising concern in recent years. The increase appears to be related at least in part to the emergence of the “USA300” S. aureus clone containing the Panton-Valentine leukocidin (PVL) genes, Dr. Sheldon L. Kaplan said at the annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.

Rates of severe infection have been rising as MRSA has become more common in the community. Recommendations from the American Academy of Pediatrics state that in areas where MRSA accounts for 10% or more of CA-MRSA isolates, initial empiric therapy of severe infections that could be due to S. aureus should include vancomycin. Naficillin should also be included because it's superior to vancomycin for treating methicillin-sensitive S. aureus (MSSA).

Use of clindamycin should be based on local susceptibility. “You need to know the clindamycin susceptibility of CA-MRSA isolates in your area,” said Dr. Kaplan, head of the pediatric infectious disease section at Baylor College of Medicine and chief of the infectious disease service at Texas Children's Hospital, both in Houston.

At Le Bonheur Children's Medical Center in Memphis, the rate of acute osteoarticular infections increased from 2.6 to 6.0 per 1,000 admissions between 2000 and 2004. While the proportion of those infections caused by MSSA remained constant at 10%–13%, those caused by MRSA rose from 4% to 40%. Moreover, 71% of the patients with MRSA had subperiosteal abscesses, compared with 38% of those with MSSA, and surgical procedures were required in 91% with MRSA versus 62% with MSSA (J. Pediatr. Orthop. 2006;26:701-2). Similar findings have been reported elsewhere, Dr. Kaplan noted.

Recent studies have shown that osteomyelitis caused by PVL-positive S. aureus strains was associated with more severe local disease and a greater systemic inflammatory response, compared with osteomyelitis caused by S. aureus not containing that gene (Pediatrics 2006;117:433-40), and that PVL-positive isolates were associated with an increased likelihood of complications in children with osteomyelitis (Pediatr. Infect. Dis. J. 2005;24:284-5).

MRI appears to be the optimal method for detection of osteomyelitis resulting from community-acquired S. aureus.

In a retrospective study by Dr. Kaplan and his associates of 199 such children seen between August 2001 and December 2006, MRI had a sensitivity of 98% for diagnosing the infection, compared with a 53% sensitivity with bone scintigraphy. Of 36 patients who had both imaging studies done, results were discordant in 17 cases. In all of those, the MRI diagnosis proved to be the correct one (Pediatr. Radiol. 2008;38:841-7).

The study also showed that MRI—but not bone scan—allowed for visualization of extraosseous complications, including subperiosteal abscesses in 77 patients, pyomyositis in 43, septic arthritis in 31, and deep vein thrombosis in 12. “Clearly, MRI was superior to bone scan in detecting bone infection. In our institution, MRI is the first thing we use. It can help pick up other areas of concern,” Dr. Kaplan noted.

Some of these extraosseous complications also appear to be on the rise. At least two recent reports have documented cases of venous thrombophlebitis among children with invasive S. aureus infections. At Children's Medical Center in Dallas, 10 of 35 children with confirmed osteomyelitis developed deep vein thrombosis during the acute infection, with evidence of dissemination in 6 (J. Pediatr. 2006;149:537-41).

And at Texas Children's, Dr. Kaplan and his associates reported on nine children seen between 1999 and 2004 who had venous thrombosis adjacent to the site of staphylococcal osteomyelitis. Seven patients had community-acquired infections caused by MRSA belonging to the same USA300 clonal group, and all seven carried PVL genes. The USA300 clone may “have a unique propensity to cause [venous thrombosis] in association with osteomyelitis,” they wrote (Pediatrics 2006;117:1673-9).

Since then, they've seen about 40-50 children with osteomyelitis who developed thrombosis, despite not having genetic prothrombotic conditions. “We don't understand what's going on. There's clearly something different about these community isolates, especially the USA300 strain,” Dr. Kaplan commented.

The USA300 MRSA genotype has also been implicated in septic arthritis. Among 44 isolates taken from 45 patients at Texas Children's with septic arthritis caused by S. aureus, 16 were MRSA; of these, 13 were USA300 and 14 were PVL-positive. Infections caused by USA300 were more likely to be associated with a longer duration of fever, bacteremia, and a C-reactive protein level of 10 mg/dL or greater (Pediatr. Infect. Dis. J. 2009;28:1076-80).

Rates of pyomyositis and myositis also have been on the rise at Texas Children's, and can be correlated to the emergence of CA-MRSA. Among 45 previously healthy children with bacterial pyomyositis or myositis, the cause was S. aureus in 58%. Of 24 community-acquired S. aureus isolates that were available, 15 were MRSA and 9 were MSSA. A total of 16 (including all the MRSA) isolates were found to be USA300, and 17 carried the PVL genes. The presence of MRSA, USA300, and/or the PVL genes was associated with a greater requirement for drainage procedures (Clin. Infect. Dis. 2006;43:953-60).

“Infection of muscles is something we just never saw in the past,” Dr. Kaplan commented.

Pulmonary manifestations are another increasingly common complication of CA-MRSA. An investigation of 70 children with invasive staphylococcal infections at Texas Children's between 2001 and 2004 showed that 47 had MRSA. Compared with 10 who had MSSA, those with MRSA were more likely to have pneumonia, empyema, lung abscess, and atelectasis. The presence of PVL was associated with abnormal chest image findings in patients with secondary pneumonia (Clin. Infect. Dis. 2005;41:583-90).

Influenza complicated by staph infections is also becoming more common, with most of these cases attributable to MRSA. A study by the Centers for Disease Control and Prevention comparing pediatric deaths during three influenza seasons revealed that bacterial coinfection increased substantially, from 6% in 2004-2005 to 15% in 2005-2006 to 34% in 2006-2007. Isolation of S. aureus from a sterile site rose from just 1 case in 2004-2005 to 22 in 2006-2007, of which two-thirds were MRSA.

Disclosures: Dr. Kaplan has received research grants from Pfizer and Cubist Pharmaceuticals.

'Infection of muscles is something we just never saw in the past.'

Source DR. KAPLAN

An axial view of proximal left tibial osteomyelitis with subperiosteal abscess and extraosseous soft tissue inflammation is shown (top). A sagittal view is also shown (bottom).

Source Images courtesy Dr. Sheldon L. Kaplan

BETHESDA, MD. — Invasive infections in children caused by community-acquired methicillin-resistant Staphylococcus aureus are on the rise.

Though still far less common than simple skin and soft tissue CA-MRSA infections, increasing reports of serious infections such as osteomyelitis, bacteremia, and pneumonia have been raising concern in recent years. The increase appears to be related at least in part to the emergence of the “USA300” S. aureus clone containing the Panton-Valentine leukocidin (PVL) genes, Dr. Sheldon L. Kaplan said at the annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.

Rates of severe infection have been rising as MRSA has become more common in the community. Recommendations from the American Academy of Pediatrics state that in areas where MRSA accounts for 10% or more of CA-MRSA isolates, initial empiric therapy of severe infections that could be due to S. aureus should include vancomycin. Naficillin should also be included because it's superior to vancomycin for treating methicillin-sensitive S. aureus (MSSA).

Use of clindamycin should be based on local susceptibility. “You need to know the clindamycin susceptibility of CA-MRSA isolates in your area,” said Dr. Kaplan, head of the pediatric infectious disease section at Baylor College of Medicine and chief of the infectious disease service at Texas Children's Hospital, both in Houston.

At Le Bonheur Children's Medical Center in Memphis, the rate of acute osteoarticular infections increased from 2.6 to 6.0 per 1,000 admissions between 2000 and 2004. While the proportion of those infections caused by MSSA remained constant at 10%–13%, those caused by MRSA rose from 4% to 40%. Moreover, 71% of the patients with MRSA had subperiosteal abscesses, compared with 38% of those with MSSA, and surgical procedures were required in 91% with MRSA versus 62% with MSSA (J. Pediatr. Orthop. 2006;26:701-2). Similar findings have been reported elsewhere, Dr. Kaplan noted.

Recent studies have shown that osteomyelitis caused by PVL-positive S. aureus strains was associated with more severe local disease and a greater systemic inflammatory response, compared with osteomyelitis caused by S. aureus not containing that gene (Pediatrics 2006;117:433-40), and that PVL-positive isolates were associated with an increased likelihood of complications in children with osteomyelitis (Pediatr. Infect. Dis. J. 2005;24:284-5).

MRI appears to be the optimal method for detection of osteomyelitis resulting from community-acquired S. aureus.

In a retrospective study by Dr. Kaplan and his associates of 199 such children seen between August 2001 and December 2006, MRI had a sensitivity of 98% for diagnosing the infection, compared with a 53% sensitivity with bone scintigraphy. Of 36 patients who had both imaging studies done, results were discordant in 17 cases. In all of those, the MRI diagnosis proved to be the correct one (Pediatr. Radiol. 2008;38:841-7).

The study also showed that MRI—but not bone scan—allowed for visualization of extraosseous complications, including subperiosteal abscesses in 77 patients, pyomyositis in 43, septic arthritis in 31, and deep vein thrombosis in 12. “Clearly, MRI was superior to bone scan in detecting bone infection. In our institution, MRI is the first thing we use. It can help pick up other areas of concern,” Dr. Kaplan noted.

Some of these extraosseous complications also appear to be on the rise. At least two recent reports have documented cases of venous thrombophlebitis among children with invasive S. aureus infections. At Children's Medical Center in Dallas, 10 of 35 children with confirmed osteomyelitis developed deep vein thrombosis during the acute infection, with evidence of dissemination in 6 (J. Pediatr. 2006;149:537-41).

And at Texas Children's, Dr. Kaplan and his associates reported on nine children seen between 1999 and 2004 who had venous thrombosis adjacent to the site of staphylococcal osteomyelitis. Seven patients had community-acquired infections caused by MRSA belonging to the same USA300 clonal group, and all seven carried PVL genes. The USA300 clone may “have a unique propensity to cause [venous thrombosis] in association with osteomyelitis,” they wrote (Pediatrics 2006;117:1673-9).

Since then, they've seen about 40-50 children with osteomyelitis who developed thrombosis, despite not having genetic prothrombotic conditions. “We don't understand what's going on. There's clearly something different about these community isolates, especially the USA300 strain,” Dr. Kaplan commented.

The USA300 MRSA genotype has also been implicated in septic arthritis. Among 44 isolates taken from 45 patients at Texas Children's with septic arthritis caused by S. aureus, 16 were MRSA; of these, 13 were USA300 and 14 were PVL-positive. Infections caused by USA300 were more likely to be associated with a longer duration of fever, bacteremia, and a C-reactive protein level of 10 mg/dL or greater (Pediatr. Infect. Dis. J. 2009;28:1076-80).

Rates of pyomyositis and myositis also have been on the rise at Texas Children's, and can be correlated to the emergence of CA-MRSA. Among 45 previously healthy children with bacterial pyomyositis or myositis, the cause was S. aureus in 58%. Of 24 community-acquired S. aureus isolates that were available, 15 were MRSA and 9 were MSSA. A total of 16 (including all the MRSA) isolates were found to be USA300, and 17 carried the PVL genes. The presence of MRSA, USA300, and/or the PVL genes was associated with a greater requirement for drainage procedures (Clin. Infect. Dis. 2006;43:953-60).

“Infection of muscles is something we just never saw in the past,” Dr. Kaplan commented.

Pulmonary manifestations are another increasingly common complication of CA-MRSA. An investigation of 70 children with invasive staphylococcal infections at Texas Children's between 2001 and 2004 showed that 47 had MRSA. Compared with 10 who had MSSA, those with MRSA were more likely to have pneumonia, empyema, lung abscess, and atelectasis. The presence of PVL was associated with abnormal chest image findings in patients with secondary pneumonia (Clin. Infect. Dis. 2005;41:583-90).

Influenza complicated by staph infections is also becoming more common, with most of these cases attributable to MRSA. A study by the Centers for Disease Control and Prevention comparing pediatric deaths during three influenza seasons revealed that bacterial coinfection increased substantially, from 6% in 2004-2005 to 15% in 2005-2006 to 34% in 2006-2007. Isolation of S. aureus from a sterile site rose from just 1 case in 2004-2005 to 22 in 2006-2007, of which two-thirds were MRSA.

Disclosures: Dr. Kaplan has received research grants from Pfizer and Cubist Pharmaceuticals.

'Infection of muscles is something we just never saw in the past.'

Source DR. KAPLAN

An axial view of proximal left tibial osteomyelitis with subperiosteal abscess and extraosseous soft tissue inflammation is shown (top). A sagittal view is also shown (bottom).

Source Images courtesy Dr. Sheldon L. Kaplan

BETHESDA, MD. — Draining abscesses and obtaining cultures are now more important to the management of pediatric skin and soft tissue infections in the era of community-acquired methicillin-resistant Staphylococcus aureus infections, according to Dr. Sheldon L. Kaplan.

Skin and soft tissue infections remain the most common manifestations of community-acquired MRSA (CA-MRSA) infection, which has increased dramatically in the past decade. Draining abscesses and obtaining cultures from purulent skin infections help physicians keep tabs on local and regional antibiotic susceptibility patterns, he said at the annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.

“It's important to send cultures, which wasn't the case years ago. It helps to know what we're dealing with on a local level,” said Dr. Kaplan, head of the pediatric infectious disease section at Baylor College of Medicine and chief of the infectious disease service at Texas Children's Hospital, both in Houston.

Although invasive CA-MRSA infections are increasingly a concern, skin and soft tissue infections continue to make up the majority of CA-MRSA infections. Among the 12,876 children with community-acquired S. aureus infections who were seen at Texas Children's between Aug. 1, 2001, and June 30, 2009, 73% had a MRSA infection. Of those, 97% were skin and soft tissue infections, compared with 93% of the methicillin-susceptible S. aureus(MSSA) infections.

Over the 8 years, children with CA-MRSA skin and soft tissue infections were more likely to be admitted to the hospital than were those with CA-MSSA isolates (58% vs. 51%).

Virtually all CA-MRSA isolates remain susceptible to trimethoprim-sulfamethoxazole (TMP-SMX), and about 90% remain susceptible to doxycycline-minocycline, although few pediatric data are available for those agents and they can be used only in children over 8 years of age, he noted.

Clindamycin susceptibility varies widely around the country. Data for 2000-2005 suggest that resistance rates in children with CA-MRSA ranged from 3% in Baltimore (Pediatr. Infect. Dis. J. 2007;26:852-4) to 22% in Chicago (Emerg. Infect. Dis. 2006;12:631-7).

In Houston, rates of clindamycin resistance have slowly increased from about 2%–3% in 2001 to approximately 10% for the last few years, Dr. Kaplan noted.

The good news is that for many abscesses, incision and drainage alone may clear the infection.

A study published a few years ago showed that this was the case for both CA-MRSA and non-MRSA staph infections. Of 69 children with skin and soft tissue abscesses caused by CA-MRSA, 62 had their abscesses drained and 45 had wound packing. All were treated with empiric antibiotics, which were ineffective in 58. After culture results were known, an antibiotic active against CA-MRSA was given to 21 of those 58. However, no significant differences in response were observed between those who never received an effective antibiotic and those who did.

Having an initial lesion larger than 5 cm was a significant predictor of hospitalization, whereas initial ineffective antibiotic therapy was not, the authors concluded (Pediatr. Infect. Dis. J. 2004;23:123-7).

And in a study presented at an infectious disease conference last year, there were no differences in response between clindamycin and cephalexin at 48-72 hours or at 7 days after surgical or spontaneous drainage among 200 children with uncomplicated skin and soft tissue infections, including the 69% of infections caused by CA-MRSA.

The researchers concluded that “antibiotic therapy may be of limited value in the management of children with uncomplicated, drained skin and soft tissue infections.”

A definitive answer to the question of how to treat uncomplicated skin and soft tissue infections may come from a current study funded by the National Institute of Allergy and Infectious Diseases, comparing TMP-SMX, clindamycin, or placebo in 1,310 nonhospitalized immunocompetent adults and children. The study began in April 2009 and is scheduled to be completed in July 2011.

“So here we are in 2010, still trying to figure out the best way to treat an abscess. Hopefully, 4-5 years from now, we'll have some information as to whether it helps to add a systemic antibiotic. We'll have to wait and see,” Dr. Kaplan commented.

Disclosures: Dr. Kaplan has received clinical research grants from Pfizer and Cubist Pharmaceuticals.

Skin and soft tissue infections, as shown by this pustule with cellulitis, are the most common CA-MRSA manifestations.

Source Courtesy Dr. Sheldon L. Kaplan

BETHESDA, MD. — Draining abscesses and obtaining cultures are now more important to the management of pediatric skin and soft tissue infections in the era of community-acquired methicillin-resistant Staphylococcus aureus infections, according to Dr. Sheldon L. Kaplan.

Skin and soft tissue infections remain the most common manifestations of community-acquired MRSA (CA-MRSA) infection, which has increased dramatically in the past decade. Draining abscesses and obtaining cultures from purulent skin infections help physicians keep tabs on local and regional antibiotic susceptibility patterns, he said at the annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.

“It's important to send cultures, which wasn't the case years ago. It helps to know what we're dealing with on a local level,” said Dr. Kaplan, head of the pediatric infectious disease section at Baylor College of Medicine and chief of the infectious disease service at Texas Children's Hospital, both in Houston.

Although invasive CA-MRSA infections are increasingly a concern, skin and soft tissue infections continue to make up the majority of CA-MRSA infections. Among the 12,876 children with community-acquired S. aureus infections who were seen at Texas Children's between Aug. 1, 2001, and June 30, 2009, 73% had a MRSA infection. Of those, 97% were skin and soft tissue infections, compared with 93% of the methicillin-susceptible S. aureus(MSSA) infections.

Over the 8 years, children with CA-MRSA skin and soft tissue infections were more likely to be admitted to the hospital than were those with CA-MSSA isolates (58% vs. 51%).

Virtually all CA-MRSA isolates remain susceptible to trimethoprim-sulfamethoxazole (TMP-SMX), and about 90% remain susceptible to doxycycline-minocycline, although few pediatric data are available for those agents and they can be used only in children over 8 years of age, he noted.

Clindamycin susceptibility varies widely around the country. Data for 2000-2005 suggest that resistance rates in children with CA-MRSA ranged from 3% in Baltimore (Pediatr. Infect. Dis. J. 2007;26:852-4) to 22% in Chicago (Emerg. Infect. Dis. 2006;12:631-7).

In Houston, rates of clindamycin resistance have slowly increased from about 2%–3% in 2001 to approximately 10% for the last few years, Dr. Kaplan noted.

The good news is that for many abscesses, incision and drainage alone may clear the infection.

A study published a few years ago showed that this was the case for both CA-MRSA and non-MRSA staph infections. Of 69 children with skin and soft tissue abscesses caused by CA-MRSA, 62 had their abscesses drained and 45 had wound packing. All were treated with empiric antibiotics, which were ineffective in 58. After culture results were known, an antibiotic active against CA-MRSA was given to 21 of those 58. However, no significant differences in response were observed between those who never received an effective antibiotic and those who did.

Having an initial lesion larger than 5 cm was a significant predictor of hospitalization, whereas initial ineffective antibiotic therapy was not, the authors concluded (Pediatr. Infect. Dis. J. 2004;23:123-7).

And in a study presented at an infectious disease conference last year, there were no differences in response between clindamycin and cephalexin at 48-72 hours or at 7 days after surgical or spontaneous drainage among 200 children with uncomplicated skin and soft tissue infections, including the 69% of infections caused by CA-MRSA.

The researchers concluded that “antibiotic therapy may be of limited value in the management of children with uncomplicated, drained skin and soft tissue infections.”

A definitive answer to the question of how to treat uncomplicated skin and soft tissue infections may come from a current study funded by the National Institute of Allergy and Infectious Diseases, comparing TMP-SMX, clindamycin, or placebo in 1,310 nonhospitalized immunocompetent adults and children. The study began in April 2009 and is scheduled to be completed in July 2011.

“So here we are in 2010, still trying to figure out the best way to treat an abscess. Hopefully, 4-5 years from now, we'll have some information as to whether it helps to add a systemic antibiotic. We'll have to wait and see,” Dr. Kaplan commented.

Disclosures: Dr. Kaplan has received clinical research grants from Pfizer and Cubist Pharmaceuticals.

Skin and soft tissue infections, as shown by this pustule with cellulitis, are the most common CA-MRSA manifestations.

Source Courtesy Dr. Sheldon L. Kaplan

BETHESDA, MD. — Draining abscesses and obtaining cultures are now more important to the management of pediatric skin and soft tissue infections in the era of community-acquired methicillin-resistant Staphylococcus aureus infections, according to Dr. Sheldon L. Kaplan.

Skin and soft tissue infections remain the most common manifestations of community-acquired MRSA (CA-MRSA) infection, which has increased dramatically in the past decade. Draining abscesses and obtaining cultures from purulent skin infections help physicians keep tabs on local and regional antibiotic susceptibility patterns, he said at the annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.

“It's important to send cultures, which wasn't the case years ago. It helps to know what we're dealing with on a local level,” said Dr. Kaplan, head of the pediatric infectious disease section at Baylor College of Medicine and chief of the infectious disease service at Texas Children's Hospital, both in Houston.

Although invasive CA-MRSA infections are increasingly a concern, skin and soft tissue infections continue to make up the majority of CA-MRSA infections. Among the 12,876 children with community-acquired S. aureus infections who were seen at Texas Children's between Aug. 1, 2001, and June 30, 2009, 73% had a MRSA infection. Of those, 97% were skin and soft tissue infections, compared with 93% of the methicillin-susceptible S. aureus(MSSA) infections.

Over the 8 years, children with CA-MRSA skin and soft tissue infections were more likely to be admitted to the hospital than were those with CA-MSSA isolates (58% vs. 51%).

Virtually all CA-MRSA isolates remain susceptible to trimethoprim-sulfamethoxazole (TMP-SMX), and about 90% remain susceptible to doxycycline-minocycline, although few pediatric data are available for those agents and they can be used only in children over 8 years of age, he noted.

Clindamycin susceptibility varies widely around the country. Data for 2000-2005 suggest that resistance rates in children with CA-MRSA ranged from 3% in Baltimore (Pediatr. Infect. Dis. J. 2007;26:852-4) to 22% in Chicago (Emerg. Infect. Dis. 2006;12:631-7).

In Houston, rates of clindamycin resistance have slowly increased from about 2%–3% in 2001 to approximately 10% for the last few years, Dr. Kaplan noted.

The good news is that for many abscesses, incision and drainage alone may clear the infection.

A study published a few years ago showed that this was the case for both CA-MRSA and non-MRSA staph infections. Of 69 children with skin and soft tissue abscesses caused by CA-MRSA, 62 had their abscesses drained and 45 had wound packing. All were treated with empiric antibiotics, which were ineffective in 58. After culture results were known, an antibiotic active against CA-MRSA was given to 21 of those 58. However, no significant differences in response were observed between those who never received an effective antibiotic and those who did.

Having an initial lesion larger than 5 cm was a significant predictor of hospitalization, whereas initial ineffective antibiotic therapy was not, the authors concluded (Pediatr. Infect. Dis. J. 2004;23:123-7).

And in a study presented at an infectious disease conference last year, there were no differences in response between clindamycin and cephalexin at 48-72 hours or at 7 days after surgical or spontaneous drainage among 200 children with uncomplicated skin and soft tissue infections, including the 69% of infections caused by CA-MRSA.

The researchers concluded that “antibiotic therapy may be of limited value in the management of children with uncomplicated, drained skin and soft tissue infections.”

A definitive answer to the question of how to treat uncomplicated skin and soft tissue infections may come from a current study funded by the National Institute of Allergy and Infectious Diseases, comparing TMP-SMX, clindamycin, or placebo in 1,310 nonhospitalized immunocompetent adults and children. The study began in April 2009 and is scheduled to be completed in July 2011.

“So here we are in 2010, still trying to figure out the best way to treat an abscess. Hopefully, 4-5 years from now, we'll have some information as to whether it helps to add a systemic antibiotic. We'll have to wait and see,” Dr. Kaplan commented.

Disclosures: Dr. Kaplan has received clinical research grants from Pfizer and Cubist Pharmaceuticals.

Skin and soft tissue infections, as shown by this pustule with cellulitis, are the most common CA-MRSA manifestations.

Source Courtesy Dr. Sheldon L. Kaplan

Major Finding: A closed-loop insulin delivery system produced more in-target glucose levels and less hypoglycemia than did standard continuous insulin infusion.

Data Source: A three-part randomized crossover study of 17 children and adolescents with type 1 diabetes.

Disclosures: The study was funded by the Juvenile Diabetes Research Foundation and three European research foundations. Dr. Hovorka has received lecture fees from Minimed Medtronic, Abbot Diabetes Care, Lifescan, Novo-Nordisk, and BBraun. He reported two patent applications. Two coinvestigators reported disclosures, while 12 others reported no competing interests. Dr. Renard stated he had no conflicts of interest.

A closed-loop system linking continuous glucose measurements to insulin delivery reduced the risk of nocturnal hypoglycemia compared with standard continuous subcutaneous insulin infusion in a three-part randomized crossover study involving 17 children and adolescents with type 1 diabetes.

Previous studies have assessed the feasibility of closed-loop insulin delivery systems that used various types of control algorithms, but this is the first to compare closed-loop delivery with traditional continuous subcutaneous insulin infusion (CSII) and the first to assess the effect of evening meals and exercise, noted Dr. Roman Hovorka, who is with the University of Cambridge (England) and his associates (Lancet 2010 Feb. 5 [doi:10.1016/S0140-6736(09)61998-X]).

“Closed-loop systems could transform management of type 1 diabetes, but their introduction is likely to be gradual, starting from straightforward applications such as shutting off the pump at low glucose concentrations or overnight closed-loop delivery, proceeding to more complex applications providing 24-[hour] control,” the investigators said.

The study subjects were aged 5-18 years and had type 1 diabetes for a mean duration of 6.4 years.

Thirteen of the children were assigned to be treated with overnight (8:00 p.m. to 8:00 a.m.) closed-loop delivery (using Medtronic's Guardian Real-Time) or standard CSII on two separate occasions.

Seven of those 13 children were also evaluated overnight with the closed-loop device (Abbott's Freestyle Navigator) on two further occasions, this time after having consumed either rapidly or slowly absorbed large meals matched for total carbohydrates (129 g), but differing in glycemic load.

In a third overnight evaluation, 10 adolescents aged 12-18 (including 4 from the first evaluation) rode a treadmill from 6:00 to 6:45 p.m. after having eaten a light meal at 4:00 p.m., again comparing closed loop (Navigator) with CSII. (All patients used Smiths Medical's Deltec Cosmo insulin pumps for the study.)

During the closed-loop nights, glucose measurements were fed every 15 minutes into a control algorithm calculating rate of insulin infusion, and a nurse adjusted the insulin pump. Standard pump settings were used on control nights.

Primary outcomes—the time for which plasma glucose concentration was in the target range of 3.91-8.00 mmol/L (70.4-144 mg/dL) or a hypoglycemic level of 3.90 mmol/L (70.2 mg/dL) or lower—did not differ significantly between closed loop and CSII for the first evaluation, Dr. Hovorka and his associates said.

The time spent in target range was 52% with closed loop versus 39% for CSII, and the time spent with hypoglycemia was 1.0% vs. 2.0%, respectively. For the exercise evaluation, the proportions for closed loop vs. CSII were 78% vs. 43% of time in target range and 10.0% vs. 6.1% of time with hypoglycemia, respectively.

For the meal comparison, there was no significant difference in overnight control between the two meals: Time spent in target range after midnight was 86% for the rapidly absorbed meal and 83% for the slowly absorbed meal. From the start of the closed-loop delivery, those proportions were 53% and 55%, respectively, Dr. Hovorka and his associates reported.

In a secondary analysis pooling the data from the first and third evaluations, closed-loop delivery significantly increased the time for which plasma glucose was in the target range (60% vs. 40%) and significantly reduced the time in hypoglycemic range (2.1% vs. 4.1%). The difference was even more significant after midnight, when closed-loop became fully effective (79% vs. 35% in target range, 3.0% vs. 6.1% hypoglycemic), they said.

In an accompanying editorial, Dr. Eric Renard of Universitaire de Montpellier, France, commented that although overall mean blood glucose concentrations were not significantly different with closed-loop delivery, the fact that the closed loop stabilized blood glucose levels overnight while keeping hypoglycemia to a minimum is “an important step forward for young patients and their parents.”

The nurses' intervention could easily be replaced by a wireless direct connection, he noted, and “the absence of any sensor or pump failure during the trials allows realistic extrapolation towards a home environment.”

However, the model predictive control algorithm used in the closed-loop system in this study will make glucose control at mealtimes more difficult than overnight control, due to the more complex effects that will need to be integrated into the model.

Proportional-integral-derivative algorithms may offer more flexibility around meals, noted Dr. Renard, who uses proportional-derivative algorithms in his own closed-loop research.

Major Finding: A closed-loop insulin delivery system produced more in-target glucose levels and less hypoglycemia than did standard continuous insulin infusion.

Data Source: A three-part randomized crossover study of 17 children and adolescents with type 1 diabetes.

Disclosures: The study was funded by the Juvenile Diabetes Research Foundation and three European research foundations. Dr. Hovorka has received lecture fees from Minimed Medtronic, Abbot Diabetes Care, Lifescan, Novo-Nordisk, and BBraun. He reported two patent applications. Two coinvestigators reported disclosures, while 12 others reported no competing interests. Dr. Renard stated he had no conflicts of interest.

A closed-loop system linking continuous glucose measurements to insulin delivery reduced the risk of nocturnal hypoglycemia compared with standard continuous subcutaneous insulin infusion in a three-part randomized crossover study involving 17 children and adolescents with type 1 diabetes.

Previous studies have assessed the feasibility of closed-loop insulin delivery systems that used various types of control algorithms, but this is the first to compare closed-loop delivery with traditional continuous subcutaneous insulin infusion (CSII) and the first to assess the effect of evening meals and exercise, noted Dr. Roman Hovorka, who is with the University of Cambridge (England) and his associates (Lancet 2010 Feb. 5 [doi:10.1016/S0140-6736(09)61998-X]).

“Closed-loop systems could transform management of type 1 diabetes, but their introduction is likely to be gradual, starting from straightforward applications such as shutting off the pump at low glucose concentrations or overnight closed-loop delivery, proceeding to more complex applications providing 24-[hour] control,” the investigators said.

The study subjects were aged 5-18 years and had type 1 diabetes for a mean duration of 6.4 years.

Thirteen of the children were assigned to be treated with overnight (8:00 p.m. to 8:00 a.m.) closed-loop delivery (using Medtronic's Guardian Real-Time) or standard CSII on two separate occasions.

Seven of those 13 children were also evaluated overnight with the closed-loop device (Abbott's Freestyle Navigator) on two further occasions, this time after having consumed either rapidly or slowly absorbed large meals matched for total carbohydrates (129 g), but differing in glycemic load.

In a third overnight evaluation, 10 adolescents aged 12-18 (including 4 from the first evaluation) rode a treadmill from 6:00 to 6:45 p.m. after having eaten a light meal at 4:00 p.m., again comparing closed loop (Navigator) with CSII. (All patients used Smiths Medical's Deltec Cosmo insulin pumps for the study.)

During the closed-loop nights, glucose measurements were fed every 15 minutes into a control algorithm calculating rate of insulin infusion, and a nurse adjusted the insulin pump. Standard pump settings were used on control nights.

Primary outcomes—the time for which plasma glucose concentration was in the target range of 3.91-8.00 mmol/L (70.4-144 mg/dL) or a hypoglycemic level of 3.90 mmol/L (70.2 mg/dL) or lower—did not differ significantly between closed loop and CSII for the first evaluation, Dr. Hovorka and his associates said.

The time spent in target range was 52% with closed loop versus 39% for CSII, and the time spent with hypoglycemia was 1.0% vs. 2.0%, respectively. For the exercise evaluation, the proportions for closed loop vs. CSII were 78% vs. 43% of time in target range and 10.0% vs. 6.1% of time with hypoglycemia, respectively.

For the meal comparison, there was no significant difference in overnight control between the two meals: Time spent in target range after midnight was 86% for the rapidly absorbed meal and 83% for the slowly absorbed meal. From the start of the closed-loop delivery, those proportions were 53% and 55%, respectively, Dr. Hovorka and his associates reported.

In a secondary analysis pooling the data from the first and third evaluations, closed-loop delivery significantly increased the time for which plasma glucose was in the target range (60% vs. 40%) and significantly reduced the time in hypoglycemic range (2.1% vs. 4.1%). The difference was even more significant after midnight, when closed-loop became fully effective (79% vs. 35% in target range, 3.0% vs. 6.1% hypoglycemic), they said.

In an accompanying editorial, Dr. Eric Renard of Universitaire de Montpellier, France, commented that although overall mean blood glucose concentrations were not significantly different with closed-loop delivery, the fact that the closed loop stabilized blood glucose levels overnight while keeping hypoglycemia to a minimum is “an important step forward for young patients and their parents.”

The nurses' intervention could easily be replaced by a wireless direct connection, he noted, and “the absence of any sensor or pump failure during the trials allows realistic extrapolation towards a home environment.”

However, the model predictive control algorithm used in the closed-loop system in this study will make glucose control at mealtimes more difficult than overnight control, due to the more complex effects that will need to be integrated into the model.

Proportional-integral-derivative algorithms may offer more flexibility around meals, noted Dr. Renard, who uses proportional-derivative algorithms in his own closed-loop research.

Major Finding: A closed-loop insulin delivery system produced more in-target glucose levels and less hypoglycemia than did standard continuous insulin infusion.

Data Source: A three-part randomized crossover study of 17 children and adolescents with type 1 diabetes.

Disclosures: The study was funded by the Juvenile Diabetes Research Foundation and three European research foundations. Dr. Hovorka has received lecture fees from Minimed Medtronic, Abbot Diabetes Care, Lifescan, Novo-Nordisk, and BBraun. He reported two patent applications. Two coinvestigators reported disclosures, while 12 others reported no competing interests. Dr. Renard stated he had no conflicts of interest.

A closed-loop system linking continuous glucose measurements to insulin delivery reduced the risk of nocturnal hypoglycemia compared with standard continuous subcutaneous insulin infusion in a three-part randomized crossover study involving 17 children and adolescents with type 1 diabetes.

Previous studies have assessed the feasibility of closed-loop insulin delivery systems that used various types of control algorithms, but this is the first to compare closed-loop delivery with traditional continuous subcutaneous insulin infusion (CSII) and the first to assess the effect of evening meals and exercise, noted Dr. Roman Hovorka, who is with the University of Cambridge (England) and his associates (Lancet 2010 Feb. 5 [doi:10.1016/S0140-6736(09)61998-X]).

“Closed-loop systems could transform management of type 1 diabetes, but their introduction is likely to be gradual, starting from straightforward applications such as shutting off the pump at low glucose concentrations or overnight closed-loop delivery, proceeding to more complex applications providing 24-[hour] control,” the investigators said.

The study subjects were aged 5-18 years and had type 1 diabetes for a mean duration of 6.4 years.

Thirteen of the children were assigned to be treated with overnight (8:00 p.m. to 8:00 a.m.) closed-loop delivery (using Medtronic's Guardian Real-Time) or standard CSII on two separate occasions.

Seven of those 13 children were also evaluated overnight with the closed-loop device (Abbott's Freestyle Navigator) on two further occasions, this time after having consumed either rapidly or slowly absorbed large meals matched for total carbohydrates (129 g), but differing in glycemic load.

In a third overnight evaluation, 10 adolescents aged 12-18 (including 4 from the first evaluation) rode a treadmill from 6:00 to 6:45 p.m. after having eaten a light meal at 4:00 p.m., again comparing closed loop (Navigator) with CSII. (All patients used Smiths Medical's Deltec Cosmo insulin pumps for the study.)

During the closed-loop nights, glucose measurements were fed every 15 minutes into a control algorithm calculating rate of insulin infusion, and a nurse adjusted the insulin pump. Standard pump settings were used on control nights.

Primary outcomes—the time for which plasma glucose concentration was in the target range of 3.91-8.00 mmol/L (70.4-144 mg/dL) or a hypoglycemic level of 3.90 mmol/L (70.2 mg/dL) or lower—did not differ significantly between closed loop and CSII for the first evaluation, Dr. Hovorka and his associates said.

The time spent in target range was 52% with closed loop versus 39% for CSII, and the time spent with hypoglycemia was 1.0% vs. 2.0%, respectively. For the exercise evaluation, the proportions for closed loop vs. CSII were 78% vs. 43% of time in target range and 10.0% vs. 6.1% of time with hypoglycemia, respectively.

For the meal comparison, there was no significant difference in overnight control between the two meals: Time spent in target range after midnight was 86% for the rapidly absorbed meal and 83% for the slowly absorbed meal. From the start of the closed-loop delivery, those proportions were 53% and 55%, respectively, Dr. Hovorka and his associates reported.

In a secondary analysis pooling the data from the first and third evaluations, closed-loop delivery significantly increased the time for which plasma glucose was in the target range (60% vs. 40%) and significantly reduced the time in hypoglycemic range (2.1% vs. 4.1%). The difference was even more significant after midnight, when closed-loop became fully effective (79% vs. 35% in target range, 3.0% vs. 6.1% hypoglycemic), they said.

In an accompanying editorial, Dr. Eric Renard of Universitaire de Montpellier, France, commented that although overall mean blood glucose concentrations were not significantly different with closed-loop delivery, the fact that the closed loop stabilized blood glucose levels overnight while keeping hypoglycemia to a minimum is “an important step forward for young patients and their parents.”

The nurses' intervention could easily be replaced by a wireless direct connection, he noted, and “the absence of any sensor or pump failure during the trials allows realistic extrapolation towards a home environment.”

However, the model predictive control algorithm used in the closed-loop system in this study will make glucose control at mealtimes more difficult than overnight control, due to the more complex effects that will need to be integrated into the model.

Proportional-integral-derivative algorithms may offer more flexibility around meals, noted Dr. Renard, who uses proportional-derivative algorithms in his own closed-loop research.

NATIONAL HARBOR, MD. — Eosinophilic esophagitis affects an estimated 52 per 100,000 Americans, while eosinophilic gastritis/colitis affects about 28 per 100,000, according to the results of the first nationwide study to investigate the disease burden of eosinophilic gastrointestinal disorders.

Previous epidemiologic studies of eosinophilic gastrointestinal disorders have been limited to specific regions of the country surrounding a tertiary referral center, with published estimates of eosinophilic esophagitis (EoE) ranging from 7.3 per 100,000 children in West Virginia (Am. J. Gastroenterol. 2007;102:2281-5) to 55 per 100,000 in Olmstead County, Minn. (Clin. Gastroenterol. Hepatol. 2009;7:1055-61).

The current study, conducted via an e-mail survey of pediatric and adult gastroenterologists, demonstrated wide variations in the rates of both EoE and eosinophilic gastritis/eosinophilic colitis (EG/EC) in different parts of the country, Dr. Wendy M. Book said at the annual meeting of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN).

Electronic surveys were e-mailed to all physician members of NASPGHAN (total 1,423), the American College of Gastroenterology (5,789), and the American Academy of Allergy, Asthma, and Immunology (3,621). The total response rate was 17%, including 866 allergy-immunology specialists, 333 pediatric gastroenterologists, and 602 adult gastroenterologists. Just over half (55%) practiced in urban settings, while 41% were suburban and 4% were rural. Fifty-nine percent were in private practice.

Analyses included only the gastroenterologists, in order to avoid possible duplication of patients. For EoE, the pediatric gastroenterologists reported seeing an average of 20.2 individual patients per year, while the adult gastroenterologists reported an average of 10.7 annually.

Based on those numbers and U.S. census data, Dr. Book said there are an estimated 158,705 patients with EoE in the United States, with a prevalence of 52.2 per 100,000 U.S. population. For EG/EC, the pediatric gastroenterologists reported seeing an average of 8.9 patients per year while the adult gastroenterologists reported 5.9/year, for an estimated 85,281, or 28.1/100,000, said Dr. Book, of the department of internal medicine at Emory University, Atlanta.

The disease burden of patients seen with EoE was highest in the U.S. Northeast, followed by the South, the Midwest, and the West.

Dr. Book is president of the nonprofit organization American Partnership for Eosinophilic Disorders (www.apfed.org

NATIONAL HARBOR, MD. — Eosinophilic esophagitis affects an estimated 52 per 100,000 Americans, while eosinophilic gastritis/colitis affects about 28 per 100,000, according to the results of the first nationwide study to investigate the disease burden of eosinophilic gastrointestinal disorders.

Previous epidemiologic studies of eosinophilic gastrointestinal disorders have been limited to specific regions of the country surrounding a tertiary referral center, with published estimates of eosinophilic esophagitis (EoE) ranging from 7.3 per 100,000 children in West Virginia (Am. J. Gastroenterol. 2007;102:2281-5) to 55 per 100,000 in Olmstead County, Minn. (Clin. Gastroenterol. Hepatol. 2009;7:1055-61).

The current study, conducted via an e-mail survey of pediatric and adult gastroenterologists, demonstrated wide variations in the rates of both EoE and eosinophilic gastritis/eosinophilic colitis (EG/EC) in different parts of the country, Dr. Wendy M. Book said at the annual meeting of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN).

Electronic surveys were e-mailed to all physician members of NASPGHAN (total 1,423), the American College of Gastroenterology (5,789), and the American Academy of Allergy, Asthma, and Immunology (3,621). The total response rate was 17%, including 866 allergy-immunology specialists, 333 pediatric gastroenterologists, and 602 adult gastroenterologists. Just over half (55%) practiced in urban settings, while 41% were suburban and 4% were rural. Fifty-nine percent were in private practice.

Analyses included only the gastroenterologists, in order to avoid possible duplication of patients. For EoE, the pediatric gastroenterologists reported seeing an average of 20.2 individual patients per year, while the adult gastroenterologists reported an average of 10.7 annually.

Based on those numbers and U.S. census data, Dr. Book said there are an estimated 158,705 patients with EoE in the United States, with a prevalence of 52.2 per 100,000 U.S. population. For EG/EC, the pediatric gastroenterologists reported seeing an average of 8.9 patients per year while the adult gastroenterologists reported 5.9/year, for an estimated 85,281, or 28.1/100,000, said Dr. Book, of the department of internal medicine at Emory University, Atlanta.

The disease burden of patients seen with EoE was highest in the U.S. Northeast, followed by the South, the Midwest, and the West.

Dr. Book is president of the nonprofit organization American Partnership for Eosinophilic Disorders (www.apfed.org

NATIONAL HARBOR, MD. — Eosinophilic esophagitis affects an estimated 52 per 100,000 Americans, while eosinophilic gastritis/colitis affects about 28 per 100,000, according to the results of the first nationwide study to investigate the disease burden of eosinophilic gastrointestinal disorders.

Previous epidemiologic studies of eosinophilic gastrointestinal disorders have been limited to specific regions of the country surrounding a tertiary referral center, with published estimates of eosinophilic esophagitis (EoE) ranging from 7.3 per 100,000 children in West Virginia (Am. J. Gastroenterol. 2007;102:2281-5) to 55 per 100,000 in Olmstead County, Minn. (Clin. Gastroenterol. Hepatol. 2009;7:1055-61).

The current study, conducted via an e-mail survey of pediatric and adult gastroenterologists, demonstrated wide variations in the rates of both EoE and eosinophilic gastritis/eosinophilic colitis (EG/EC) in different parts of the country, Dr. Wendy M. Book said at the annual meeting of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN).

Electronic surveys were e-mailed to all physician members of NASPGHAN (total 1,423), the American College of Gastroenterology (5,789), and the American Academy of Allergy, Asthma, and Immunology (3,621). The total response rate was 17%, including 866 allergy-immunology specialists, 333 pediatric gastroenterologists, and 602 adult gastroenterologists. Just over half (55%) practiced in urban settings, while 41% were suburban and 4% were rural. Fifty-nine percent were in private practice.

Analyses included only the gastroenterologists, in order to avoid possible duplication of patients. For EoE, the pediatric gastroenterologists reported seeing an average of 20.2 individual patients per year, while the adult gastroenterologists reported an average of 10.7 annually.

Based on those numbers and U.S. census data, Dr. Book said there are an estimated 158,705 patients with EoE in the United States, with a prevalence of 52.2 per 100,000 U.S. population. For EG/EC, the pediatric gastroenterologists reported seeing an average of 8.9 patients per year while the adult gastroenterologists reported 5.9/year, for an estimated 85,281, or 28.1/100,000, said Dr. Book, of the department of internal medicine at Emory University, Atlanta.

The disease burden of patients seen with EoE was highest in the U.S. Northeast, followed by the South, the Midwest, and the West.

Dr. Book is president of the nonprofit organization American Partnership for Eosinophilic Disorders (www.apfed.org

NATIONAL HARBOR, MD. – Abdominal migraine might be responsible for up to 15% of all cases of idiopathic recurrent abdominal pain in children, according to an analysis of records from more than 400 children.

Abdominal migraine is an idiopathic disorder that is characterized by moderate to severe midline abdominal pain lasting 1-72 hours associated with vasomotor symptoms, nausea, and vomiting. It is recognized by the International Headache Society (IHS) as being among the “periodic syndromes of childhood that are commonly precursors of migraine” (Cephalagia 2004;24:suppl 1:9-160).

Most of the literature on the topic is from Europe, and the diagnosis is far more common there than it is in the United States, where it is largely underdiagnosed, Dr. Laura D. Carson and her associates reported in a poster she presented at the annual meeting of the North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition.

In a retrospective chart study of 600 children and young adults (ages 1-21 years, 59% female) who were referred to a pediatric gastroenterologist during 2006-2007 for recurrent abdominal pain, 23.5% (141) were excluded because of a preexisting diagnosis.

Of 458 children who met inclusion criteria, 4% (20) met the IHS diagnostic criteria for abdominal migraine, while another 11% (50) were considered probable diagnoses of abdominal migraine with documentation lacking for at least one diagnostic criterion. The remaining 85% (388) did not meet the criteria, said Dr. Carson and her associates, of Eastern Virginia Medical School and Children's Hospital of the King's Daughters, both in Norfolk, Va.

In an interview, Dr. Carson said no significant relationship was identified among those with abdominal migraine and those who had family histories of either abdominal pain or headache. However, children who met the abdominal migraine criteria were four times more likely to have migraine headache themselves.

Despite its inclusion in both the IHS classification as well as inclusion in the 2006 Rome III GI Criteria (Gastroenterology 2006;130:1527-37), abdominal migraine is infrequently considered in the differential diagnosis of recurrent abdominal pain in children. Part of the problem is that expertise in migraine lies with neurologists, who are rarely called upon to evaluate abdominal pain.

Abdominal migraine occurs only in children, whereas in adulthood it presents to neurologists as classic migraine headache. Children with recurrent abdominal pain often are referred to gastroenterologists, who rule out other organic causes but might not consider migraine as an etiology.

“Given the spectrum of treatment modalities now available for pediatric migraine, increased awareness of cardinal features of abdominal migraine by pediatricians and pediatric gastroenterologists may result in improved diagnostic accuracy and early institution of both acute and preventative migraine-specific treatments,” Dr. Carson and her associates said in their poster.

This study was funded by the Children's Specialty Group Chairman's Fund, based at Children's Hospital of the King's Daughters, Norfolk. Dr. Carson stated that she had no other financial disclosures.

NATIONAL HARBOR, MD. – Abdominal migraine might be responsible for up to 15% of all cases of idiopathic recurrent abdominal pain in children, according to an analysis of records from more than 400 children.

Abdominal migraine is an idiopathic disorder that is characterized by moderate to severe midline abdominal pain lasting 1-72 hours associated with vasomotor symptoms, nausea, and vomiting. It is recognized by the International Headache Society (IHS) as being among the “periodic syndromes of childhood that are commonly precursors of migraine” (Cephalagia 2004;24:suppl 1:9-160).

Most of the literature on the topic is from Europe, and the diagnosis is far more common there than it is in the United States, where it is largely underdiagnosed, Dr. Laura D. Carson and her associates reported in a poster she presented at the annual meeting of the North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition.

In a retrospective chart study of 600 children and young adults (ages 1-21 years, 59% female) who were referred to a pediatric gastroenterologist during 2006-2007 for recurrent abdominal pain, 23.5% (141) were excluded because of a preexisting diagnosis.

Of 458 children who met inclusion criteria, 4% (20) met the IHS diagnostic criteria for abdominal migraine, while another 11% (50) were considered probable diagnoses of abdominal migraine with documentation lacking for at least one diagnostic criterion. The remaining 85% (388) did not meet the criteria, said Dr. Carson and her associates, of Eastern Virginia Medical School and Children's Hospital of the King's Daughters, both in Norfolk, Va.

In an interview, Dr. Carson said no significant relationship was identified among those with abdominal migraine and those who had family histories of either abdominal pain or headache. However, children who met the abdominal migraine criteria were four times more likely to have migraine headache themselves.

Despite its inclusion in both the IHS classification as well as inclusion in the 2006 Rome III GI Criteria (Gastroenterology 2006;130:1527-37), abdominal migraine is infrequently considered in the differential diagnosis of recurrent abdominal pain in children. Part of the problem is that expertise in migraine lies with neurologists, who are rarely called upon to evaluate abdominal pain.

Abdominal migraine occurs only in children, whereas in adulthood it presents to neurologists as classic migraine headache. Children with recurrent abdominal pain often are referred to gastroenterologists, who rule out other organic causes but might not consider migraine as an etiology.

“Given the spectrum of treatment modalities now available for pediatric migraine, increased awareness of cardinal features of abdominal migraine by pediatricians and pediatric gastroenterologists may result in improved diagnostic accuracy and early institution of both acute and preventative migraine-specific treatments,” Dr. Carson and her associates said in their poster.

This study was funded by the Children's Specialty Group Chairman's Fund, based at Children's Hospital of the King's Daughters, Norfolk. Dr. Carson stated that she had no other financial disclosures.

NATIONAL HARBOR, MD. – Abdominal migraine might be responsible for up to 15% of all cases of idiopathic recurrent abdominal pain in children, according to an analysis of records from more than 400 children.

Abdominal migraine is an idiopathic disorder that is characterized by moderate to severe midline abdominal pain lasting 1-72 hours associated with vasomotor symptoms, nausea, and vomiting. It is recognized by the International Headache Society (IHS) as being among the “periodic syndromes of childhood that are commonly precursors of migraine” (Cephalagia 2004;24:suppl 1:9-160).

Most of the literature on the topic is from Europe, and the diagnosis is far more common there than it is in the United States, where it is largely underdiagnosed, Dr. Laura D. Carson and her associates reported in a poster she presented at the annual meeting of the North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition.

In a retrospective chart study of 600 children and young adults (ages 1-21 years, 59% female) who were referred to a pediatric gastroenterologist during 2006-2007 for recurrent abdominal pain, 23.5% (141) were excluded because of a preexisting diagnosis.

Of 458 children who met inclusion criteria, 4% (20) met the IHS diagnostic criteria for abdominal migraine, while another 11% (50) were considered probable diagnoses of abdominal migraine with documentation lacking for at least one diagnostic criterion. The remaining 85% (388) did not meet the criteria, said Dr. Carson and her associates, of Eastern Virginia Medical School and Children's Hospital of the King's Daughters, both in Norfolk, Va.

In an interview, Dr. Carson said no significant relationship was identified among those with abdominal migraine and those who had family histories of either abdominal pain or headache. However, children who met the abdominal migraine criteria were four times more likely to have migraine headache themselves.

Despite its inclusion in both the IHS classification as well as inclusion in the 2006 Rome III GI Criteria (Gastroenterology 2006;130:1527-37), abdominal migraine is infrequently considered in the differential diagnosis of recurrent abdominal pain in children. Part of the problem is that expertise in migraine lies with neurologists, who are rarely called upon to evaluate abdominal pain.

Abdominal migraine occurs only in children, whereas in adulthood it presents to neurologists as classic migraine headache. Children with recurrent abdominal pain often are referred to gastroenterologists, who rule out other organic causes but might not consider migraine as an etiology.

“Given the spectrum of treatment modalities now available for pediatric migraine, increased awareness of cardinal features of abdominal migraine by pediatricians and pediatric gastroenterologists may result in improved diagnostic accuracy and early institution of both acute and preventative migraine-specific treatments,” Dr. Carson and her associates said in their poster.

This study was funded by the Children's Specialty Group Chairman's Fund, based at Children's Hospital of the King's Daughters, Norfolk. Dr. Carson stated that she had no other financial disclosures.

WASHINGTON – A history of severe hypoglycemic episodes was associated with an increased risk for dementia in a longitudinal cohort study involving 16,667 older patients with type 2 diabetes.

“Severe hypoglycemic episodes might be associated with a neurological consequence in a population that is already at greater risk for dementia. …This study also adds to the evidence base that balance of glycemic control is a critical issue, particularly for the elderly,” Rachel A. Whitmer, Ph.D., said at a press briefing timed to coincide with publication of the special diabetes edition of the Journal of the American Medical Association.

The study, which retrospectively analyzed data from the Kaiser Permanente Northern California Diabetes Registry, identified a 2.39% increase in absolute risk of dementia per year of follow-up for patients with a history of hypoglycemia that resulted in hospitalization or an emergency department visit, compared with type 2 diabetic patients without such a history.

“Trying to aim for a very low glycemic target might not be beneficial and might even be harmful. We know that high blood sugar isn't good, but I think the message here is also that very low levels aren't good,” added Dr. Whitmer of Kaiser Permanente's division of research.

Because the data analyses included two methods by which the hypoglycemia events were separated in time from the onset of dementia, the study supports the direction of causality that the hypoglycemia preceded the dementia, rather than the other way around. Moreover, “Our findings were independent of glycemic control as assessed by levels of [hemoglobin A_1c], type of diabetes treatment, and diabetes comorbidities,” wrote Dr. Whitmer and her associates in the published report (JAMA 2009;301:1565-72).

The patients were all aged 55 or older on Jan. 1, 2003, with no signs of dementia at that time. A total of 11% (1,822) patients were diagnosed with dementia during a mean follow-up of 3.8 years and a median follow-up of 4.8 years, and a total of 8.8% (1,465) had at least one episode of severe hypoglycemia during 1980-2002. Of those 1,465, 68.5% had one such episode, 1% had two, and 13.5% had three or more.

Age-adjusted incidence rates of dementia by frequency of severe hypoglycemic episodes were significantly higher among those with at least one episode, compared with those with no such episodes (566.8 vs. 327.6 per 10,000 person-years), with an attributable risk of 2.4% per year.

After adjustment for age, body mass index, race/ethnicity, education, sex, and diabetes duration, the hazard ratios for dementia, compared with patients who had no severe hypoglycemic episodes were 1.7 for those with at least one episode, 2.2 for two or more, and 2.6 for three or more episodes. Further adjustment for diabetes-related comorbidity, HbA_1c level, diabetes treatment, and years of insulin use modestly attenuated the effect but it remained “statistically significant and clinically relevant” with hazard ratios of 1.3, 1.8, and 1.9, respectively, Dr. Whitmer and her associates said.

Trends were similar when only the incident dementia cases diagnosed between Jan. 1, 2005, and Jan. 15, 2007, were considered after adjustment for all the above-mentioned factors, with hazard ratios of 1.2 for at least one severe hypoglycemia episode, 1.7 for two or more episodes, and 2.1 for three or more episodes, compared with patients who had no such episodes. Another “backward lag model” analysis that examined only the impact of hypoglycemic events occurring from 1980 through 1985 also identified the same trend, with a hazard ratio of 1.3 for one or more episodes.

Other analyses, including adjustment for other variables indicative of diabetes severity, length of health plan membership, time since initial diabetes diagnosis, and medical utilization rate also yielded similar results, although there was some mild attenuation for patients with three or more episodes, the investigators said.

Possible mechanisms by which hypoglycemia might increase the risk of subsequent dementia in older individuals include neuronal death and/or increased platelet aggregation/fibrinogen formation. Cerebrovascular disease is another possibility, even though another analysis adjusting for acute stroke and transient cerebral ischemia in this study population did not fully account for the effect of hypoglycemia. Given evidence from animals, “cerebrovascular damage is likely one of the mechanisms,” they noted.

Moreover, while hypoglycemia was not found to be associated with higher risk of subsequent impairment among the young adults with type 1 diabetes in the Diabetes Control and Complications Trial, “older individuals are thought to have less brain reserve or brain plasticity and therefore may be unable to recover from neurologic insult as well as younger individuals are able to,” Dr. Whitmer and her associates said.

This study was funded by the National Institutes of Health. None of the investigators disclosed any conflicts of interest.

WASHINGTON – A history of severe hypoglycemic episodes was associated with an increased risk for dementia in a longitudinal cohort study involving 16,667 older patients with type 2 diabetes.

“Severe hypoglycemic episodes might be associated with a neurological consequence in a population that is already at greater risk for dementia. …This study also adds to the evidence base that balance of glycemic control is a critical issue, particularly for the elderly,” Rachel A. Whitmer, Ph.D., said at a press briefing timed to coincide with publication of the special diabetes edition of the Journal of the American Medical Association.

The study, which retrospectively analyzed data from the Kaiser Permanente Northern California Diabetes Registry, identified a 2.39% increase in absolute risk of dementia per year of follow-up for patients with a history of hypoglycemia that resulted in hospitalization or an emergency department visit, compared with type 2 diabetic patients without such a history.

“Trying to aim for a very low glycemic target might not be beneficial and might even be harmful. We know that high blood sugar isn't good, but I think the message here is also that very low levels aren't good,” added Dr. Whitmer of Kaiser Permanente's division of research.

Because the data analyses included two methods by which the hypoglycemia events were separated in time from the onset of dementia, the study supports the direction of causality that the hypoglycemia preceded the dementia, rather than the other way around. Moreover, “Our findings were independent of glycemic control as assessed by levels of [hemoglobin A_1c], type of diabetes treatment, and diabetes comorbidities,” wrote Dr. Whitmer and her associates in the published report (JAMA 2009;301:1565-72).

The patients were all aged 55 or older on Jan. 1, 2003, with no signs of dementia at that time. A total of 11% (1,822) patients were diagnosed with dementia during a mean follow-up of 3.8 years and a median follow-up of 4.8 years, and a total of 8.8% (1,465) had at least one episode of severe hypoglycemia during 1980-2002. Of those 1,465, 68.5% had one such episode, 1% had two, and 13.5% had three or more.

Age-adjusted incidence rates of dementia by frequency of severe hypoglycemic episodes were significantly higher among those with at least one episode, compared with those with no such episodes (566.8 vs. 327.6 per 10,000 person-years), with an attributable risk of 2.4% per year.

After adjustment for age, body mass index, race/ethnicity, education, sex, and diabetes duration, the hazard ratios for dementia, compared with patients who had no severe hypoglycemic episodes were 1.7 for those with at least one episode, 2.2 for two or more, and 2.6 for three or more episodes. Further adjustment for diabetes-related comorbidity, HbA_1c level, diabetes treatment, and years of insulin use modestly attenuated the effect but it remained “statistically significant and clinically relevant” with hazard ratios of 1.3, 1.8, and 1.9, respectively, Dr. Whitmer and her associates said.

Trends were similar when only the incident dementia cases diagnosed between Jan. 1, 2005, and Jan. 15, 2007, were considered after adjustment for all the above-mentioned factors, with hazard ratios of 1.2 for at least one severe hypoglycemia episode, 1.7 for two or more episodes, and 2.1 for three or more episodes, compared with patients who had no such episodes. Another “backward lag model” analysis that examined only the impact of hypoglycemic events occurring from 1980 through 1985 also identified the same trend, with a hazard ratio of 1.3 for one or more episodes.

Other analyses, including adjustment for other variables indicative of diabetes severity, length of health plan membership, time since initial diabetes diagnosis, and medical utilization rate also yielded similar results, although there was some mild attenuation for patients with three or more episodes, the investigators said.

Possible mechanisms by which hypoglycemia might increase the risk of subsequent dementia in older individuals include neuronal death and/or increased platelet aggregation/fibrinogen formation. Cerebrovascular disease is another possibility, even though another analysis adjusting for acute stroke and transient cerebral ischemia in this study population did not fully account for the effect of hypoglycemia. Given evidence from animals, “cerebrovascular damage is likely one of the mechanisms,” they noted.

Moreover, while hypoglycemia was not found to be associated with higher risk of subsequent impairment among the young adults with type 1 diabetes in the Diabetes Control and Complications Trial, “older individuals are thought to have less brain reserve or brain plasticity and therefore may be unable to recover from neurologic insult as well as younger individuals are able to,” Dr. Whitmer and her associates said.

This study was funded by the National Institutes of Health. None of the investigators disclosed any conflicts of interest.

WASHINGTON – A history of severe hypoglycemic episodes was associated with an increased risk for dementia in a longitudinal cohort study involving 16,667 older patients with type 2 diabetes.

“Severe hypoglycemic episodes might be associated with a neurological consequence in a population that is already at greater risk for dementia. …This study also adds to the evidence base that balance of glycemic control is a critical issue, particularly for the elderly,” Rachel A. Whitmer, Ph.D., said at a press briefing timed to coincide with publication of the special diabetes edition of the Journal of the American Medical Association.

The study, which retrospectively analyzed data from the Kaiser Permanente Northern California Diabetes Registry, identified a 2.39% increase in absolute risk of dementia per year of follow-up for patients with a history of hypoglycemia that resulted in hospitalization or an emergency department visit, compared with type 2 diabetic patients without such a history.

“Trying to aim for a very low glycemic target might not be beneficial and might even be harmful. We know that high blood sugar isn't good, but I think the message here is also that very low levels aren't good,” added Dr. Whitmer of Kaiser Permanente's division of research.

Because the data analyses included two methods by which the hypoglycemia events were separated in time from the onset of dementia, the study supports the direction of causality that the hypoglycemia preceded the dementia, rather than the other way around. Moreover, “Our findings were independent of glycemic control as assessed by levels of [hemoglobin A_1c], type of diabetes treatment, and diabetes comorbidities,” wrote Dr. Whitmer and her associates in the published report (JAMA 2009;301:1565-72).

The patients were all aged 55 or older on Jan. 1, 2003, with no signs of dementia at that time. A total of 11% (1,822) patients were diagnosed with dementia during a mean follow-up of 3.8 years and a median follow-up of 4.8 years, and a total of 8.8% (1,465) had at least one episode of severe hypoglycemia during 1980-2002. Of those 1,465, 68.5% had one such episode, 1% had two, and 13.5% had three or more.

Age-adjusted incidence rates of dementia by frequency of severe hypoglycemic episodes were significantly higher among those with at least one episode, compared with those with no such episodes (566.8 vs. 327.6 per 10,000 person-years), with an attributable risk of 2.4% per year.

After adjustment for age, body mass index, race/ethnicity, education, sex, and diabetes duration, the hazard ratios for dementia, compared with patients who had no severe hypoglycemic episodes were 1.7 for those with at least one episode, 2.2 for two or more, and 2.6 for three or more episodes. Further adjustment for diabetes-related comorbidity, HbA_1c level, diabetes treatment, and years of insulin use modestly attenuated the effect but it remained “statistically significant and clinically relevant” with hazard ratios of 1.3, 1.8, and 1.9, respectively, Dr. Whitmer and her associates said.

Trends were similar when only the incident dementia cases diagnosed between Jan. 1, 2005, and Jan. 15, 2007, were considered after adjustment for all the above-mentioned factors, with hazard ratios of 1.2 for at least one severe hypoglycemia episode, 1.7 for two or more episodes, and 2.1 for three or more episodes, compared with patients who had no such episodes. Another “backward lag model” analysis that examined only the impact of hypoglycemic events occurring from 1980 through 1985 also identified the same trend, with a hazard ratio of 1.3 for one or more episodes.

Other analyses, including adjustment for other variables indicative of diabetes severity, length of health plan membership, time since initial diabetes diagnosis, and medical utilization rate also yielded similar results, although there was some mild attenuation for patients with three or more episodes, the investigators said.

Possible mechanisms by which hypoglycemia might increase the risk of subsequent dementia in older individuals include neuronal death and/or increased platelet aggregation/fibrinogen formation. Cerebrovascular disease is another possibility, even though another analysis adjusting for acute stroke and transient cerebral ischemia in this study population did not fully account for the effect of hypoglycemia. Given evidence from animals, “cerebrovascular damage is likely one of the mechanisms,” they noted.

Moreover, while hypoglycemia was not found to be associated with higher risk of subsequent impairment among the young adults with type 1 diabetes in the Diabetes Control and Complications Trial, “older individuals are thought to have less brain reserve or brain plasticity and therefore may be unable to recover from neurologic insult as well as younger individuals are able to,” Dr. Whitmer and her associates said.

This study was funded by the National Institutes of Health. None of the investigators disclosed any conflicts of interest.

BETHESDA, MD. — Draining abscesses and obtaining cultures are now more important to the management of pediatric skin and soft tissue infections in the era of community-acquired methicillin-resistant Staphylococcus aureus infections.

Skin and soft tissue infections remain the most common manifestations of community-acquired MRSA (CA-MRSA) infection, which has increased dramatically in the past decade. Draining abscesses and obtaining cultures from purulent skin infections helps physicians keep tabs on local and regional antibiotic susceptibility patterns, Dr. Sheldon L. Kaplan said at the annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.

“It's important to send cultures, which wasn't the case years ago. It helps to know what we're dealing with on a local level,” said Dr. Kaplan, head of the pediatric infectious disease section at Baylor College of Medicine and chief of the infectious disease service at Texas Children's Hospital, both in Houston.

Although invasive CA-MRSA infections are increasingly a concern, skin and soft tissue infections continue to make up the majority of CA-MRSA infections. Among the 12,876 children with community-acquired S. aureus infections who were seen at Texas Children's between Aug. 1, 2001, and June 30, 2009, 73% had a MRSA infection. Of those, 97% were skin and soft tissue infections, compared with 93% of the methicillin-susceptible S. aureus (MSSA) infections.

Over the 8 years, children with CA-MRSA skin and soft tissue infections were more likely to be admitted to the hospital than were those with CA-MSSA isolates (58% vs. 51%).

Virtually all CA-MRSA isolates remain susceptible to trimethoprim-sulfamethoxazole (TMP-SMX), and about 90% remain susceptible to doxycycline-minocycline, although few pediatric data are available for those agents and they can be used only in children over 8 years of age, Dr. Kaplan noted.

Clindamycin susceptibility varies widely around the country. Data from 2000–2005 suggest that resistance rates in children with CA-MRSA ranged from 3% in Baltimore (Pediatr. Infect. Dis. J. 2007;26:852–4) to 22% in Chicago (Emerg. Infect. Dis. 2006;12:631–7).

In Houston, rates of clindamycin resistance have slowly increased from about 2%–3% in 2001 to approximately 10% for the last few years, Dr. Kaplan noted.

The good news is that for many abscesses, incision and drainage alone may clear the infection.

A study published a few years ago showed that this was the case for both CA-MRSA and non-MRSA staph infections. Of 69 children with skin and soft tissue abscesses caused by CA-MRSA, 62 had their abscesses drained and 45 had wound packing. All of the children were treated with empiric antibiotics, which were ineffective in 58.

After the culture results were known, an antibiotic active against CA-MRSA was given to 21 of those 58.

However, no significant differences in response were observed between those who never received an effective antibiotic and those who did.

Having an initial lesion larger than 5 cm was a significant predictor of hospitalization, whereas initial ineffective antibiotic therapy was not, the authors concluded (Pediatr. Infect. Dis. J. 2004;23:123–7).

And in a study presented at an infectious disease conference last year, there were no differences in response between clindamycin and cephalexin at 48–72 hours or at 7 days after surgical or spontaneous drainage among 200 children with uncomplicated skin and soft tissue infections, including the 69% of infections caused by CA-MRSA.

The researchers concluded that “antibiotic therapy may be of limited value in the management of children with uncomplicated, drained skin and soft tissue infections.”

A definitive answer to the question of how to treat uncomplicated skin and soft tissue infections may come from a current study funded by the National Institute of Allergy and Infectious Diseases, comparing TMP-SMX, clindamycin, or placebo in 1,310 nonhospitalized immunocompetent adults and children. The study, which began in April 2009, is scheduled to be completed in July 2011, Dr. Kaplan said.

“So here we are in 2010, still trying to figure out the best way to treat an abscess,” he commented.

“Hopefully, 4–5 years from now, we'll have some information as to whether it helps to add a systemic antibiotic. We'll have to wait and see,” Dr. Kaplan added.

Disclosures: Dr. Kaplan has received clinical research grants from Pfizer and Cubist Pharmaceuticals.

'It's important to send cultures, which wasn't the case years ago. It helps to know what we're dealing with.'

Source DR. KAPLAN

BETHESDA, MD. — Draining abscesses and obtaining cultures are now more important to the management of pediatric skin and soft tissue infections in the era of community-acquired methicillin-resistant Staphylococcus aureus infections.

Skin and soft tissue infections remain the most common manifestations of community-acquired MRSA (CA-MRSA) infection, which has increased dramatically in the past decade. Draining abscesses and obtaining cultures from purulent skin infections helps physicians keep tabs on local and regional antibiotic susceptibility patterns, Dr. Sheldon L. Kaplan said at the annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.

“It's important to send cultures, which wasn't the case years ago. It helps to know what we're dealing with on a local level,” said Dr. Kaplan, head of the pediatric infectious disease section at Baylor College of Medicine and chief of the infectious disease service at Texas Children's Hospital, both in Houston.

Although invasive CA-MRSA infections are increasingly a concern, skin and soft tissue infections continue to make up the majority of CA-MRSA infections. Among the 12,876 children with community-acquired S. aureus infections who were seen at Texas Children's between Aug. 1, 2001, and June 30, 2009, 73% had a MRSA infection. Of those, 97% were skin and soft tissue infections, compared with 93% of the methicillin-susceptible S. aureus (MSSA) infections.

Over the 8 years, children with CA-MRSA skin and soft tissue infections were more likely to be admitted to the hospital than were those with CA-MSSA isolates (58% vs. 51%).

Virtually all CA-MRSA isolates remain susceptible to trimethoprim-sulfamethoxazole (TMP-SMX), and about 90% remain susceptible to doxycycline-minocycline, although few pediatric data are available for those agents and they can be used only in children over 8 years of age, Dr. Kaplan noted.

Clindamycin susceptibility varies widely around the country. Data from 2000–2005 suggest that resistance rates in children with CA-MRSA ranged from 3% in Baltimore (Pediatr. Infect. Dis. J. 2007;26:852–4) to 22% in Chicago (Emerg. Infect. Dis. 2006;12:631–7).

In Houston, rates of clindamycin resistance have slowly increased from about 2%–3% in 2001 to approximately 10% for the last few years, Dr. Kaplan noted.

The good news is that for many abscesses, incision and drainage alone may clear the infection.

A study published a few years ago showed that this was the case for both CA-MRSA and non-MRSA staph infections. Of 69 children with skin and soft tissue abscesses caused by CA-MRSA, 62 had their abscesses drained and 45 had wound packing. All of the children were treated with empiric antibiotics, which were ineffective in 58.

After the culture results were known, an antibiotic active against CA-MRSA was given to 21 of those 58.

However, no significant differences in response were observed between those who never received an effective antibiotic and those who did.

Having an initial lesion larger than 5 cm was a significant predictor of hospitalization, whereas initial ineffective antibiotic therapy was not, the authors concluded (Pediatr. Infect. Dis. J. 2004;23:123–7).

And in a study presented at an infectious disease conference last year, there were no differences in response between clindamycin and cephalexin at 48–72 hours or at 7 days after surgical or spontaneous drainage among 200 children with uncomplicated skin and soft tissue infections, including the 69% of infections caused by CA-MRSA.

The researchers concluded that “antibiotic therapy may be of limited value in the management of children with uncomplicated, drained skin and soft tissue infections.”

A definitive answer to the question of how to treat uncomplicated skin and soft tissue infections may come from a current study funded by the National Institute of Allergy and Infectious Diseases, comparing TMP-SMX, clindamycin, or placebo in 1,310 nonhospitalized immunocompetent adults and children. The study, which began in April 2009, is scheduled to be completed in July 2011, Dr. Kaplan said.

“So here we are in 2010, still trying to figure out the best way to treat an abscess,” he commented.

“Hopefully, 4–5 years from now, we'll have some information as to whether it helps to add a systemic antibiotic. We'll have to wait and see,” Dr. Kaplan added.

Disclosures: Dr. Kaplan has received clinical research grants from Pfizer and Cubist Pharmaceuticals.

'It's important to send cultures, which wasn't the case years ago. It helps to know what we're dealing with.'

Source DR. KAPLAN

BETHESDA, MD. — Draining abscesses and obtaining cultures are now more important to the management of pediatric skin and soft tissue infections in the era of community-acquired methicillin-resistant Staphylococcus aureus infections.

Skin and soft tissue infections remain the most common manifestations of community-acquired MRSA (CA-MRSA) infection, which has increased dramatically in the past decade. Draining abscesses and obtaining cultures from purulent skin infections helps physicians keep tabs on local and regional antibiotic susceptibility patterns, Dr. Sheldon L. Kaplan said at the annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.

“It's important to send cultures, which wasn't the case years ago. It helps to know what we're dealing with on a local level,” said Dr. Kaplan, head of the pediatric infectious disease section at Baylor College of Medicine and chief of the infectious disease service at Texas Children's Hospital, both in Houston.

Although invasive CA-MRSA infections are increasingly a concern, skin and soft tissue infections continue to make up the majority of CA-MRSA infections. Among the 12,876 children with community-acquired S. aureus infections who were seen at Texas Children's between Aug. 1, 2001, and June 30, 2009, 73% had a MRSA infection. Of those, 97% were skin and soft tissue infections, compared with 93% of the methicillin-susceptible S. aureus (MSSA) infections.

Over the 8 years, children with CA-MRSA skin and soft tissue infections were more likely to be admitted to the hospital than were those with CA-MSSA isolates (58% vs. 51%).

Virtually all CA-MRSA isolates remain susceptible to trimethoprim-sulfamethoxazole (TMP-SMX), and about 90% remain susceptible to doxycycline-minocycline, although few pediatric data are available for those agents and they can be used only in children over 8 years of age, Dr. Kaplan noted.

Clindamycin susceptibility varies widely around the country. Data from 2000–2005 suggest that resistance rates in children with CA-MRSA ranged from 3% in Baltimore (Pediatr. Infect. Dis. J. 2007;26:852–4) to 22% in Chicago (Emerg. Infect. Dis. 2006;12:631–7).

In Houston, rates of clindamycin resistance have slowly increased from about 2%–3% in 2001 to approximately 10% for the last few years, Dr. Kaplan noted.

The good news is that for many abscesses, incision and drainage alone may clear the infection.

A study published a few years ago showed that this was the case for both CA-MRSA and non-MRSA staph infections. Of 69 children with skin and soft tissue abscesses caused by CA-MRSA, 62 had their abscesses drained and 45 had wound packing. All of the children were treated with empiric antibiotics, which were ineffective in 58.

After the culture results were known, an antibiotic active against CA-MRSA was given to 21 of those 58.

However, no significant differences in response were observed between those who never received an effective antibiotic and those who did.

Having an initial lesion larger than 5 cm was a significant predictor of hospitalization, whereas initial ineffective antibiotic therapy was not, the authors concluded (Pediatr. Infect. Dis. J. 2004;23:123–7).

And in a study presented at an infectious disease conference last year, there were no differences in response between clindamycin and cephalexin at 48–72 hours or at 7 days after surgical or spontaneous drainage among 200 children with uncomplicated skin and soft tissue infections, including the 69% of infections caused by CA-MRSA.

The researchers concluded that “antibiotic therapy may be of limited value in the management of children with uncomplicated, drained skin and soft tissue infections.”

A definitive answer to the question of how to treat uncomplicated skin and soft tissue infections may come from a current study funded by the National Institute of Allergy and Infectious Diseases, comparing TMP-SMX, clindamycin, or placebo in 1,310 nonhospitalized immunocompetent adults and children. The study, which began in April 2009, is scheduled to be completed in July 2011, Dr. Kaplan said.

“So here we are in 2010, still trying to figure out the best way to treat an abscess,” he commented.

“Hopefully, 4–5 years from now, we'll have some information as to whether it helps to add a systemic antibiotic. We'll have to wait and see,” Dr. Kaplan added.

Disclosures: Dr. Kaplan has received clinical research grants from Pfizer and Cubist Pharmaceuticals.

'It's important to send cultures, which wasn't the case years ago. It helps to know what we're dealing with.'

Source DR. KAPLAN

BETHESDA, MD. — Invasive infections in children caused by community-acquired methicillin-resistant Staphylococcus aureus are on the rise.

Though still far less common than simple skin and soft tissue CA-MRSA infections, increasing reports of serious infections such as osteomyelitis, bacteremia, and pneumonia have been raising concern in recent years. The increase appears to be related at least in part to the emergence of the “USA300” S. aureus clone containing the Panton-Valentine leukocidin (PVL) genes, Dr. Sheldon L. Kaplan said at the annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.

Rates of severe infection have been rising as MRSA has become more common in the community. Recommendations from the American Academy of Pediatrics state that in areas where MRSA accounts for 10% or more of CA-MRSA isolates, initial empiric therapy of severe infections that could be due to S. aureus should include vancomycin. Naficillin should also be included because it's superior to vancomycin for treating methicillin-sensitive S. aureus (MSSA).

Use of clindamycin should be based on local susceptibility. “You need to know the clindamycin susceptibility of CA-MRSA isolates in your area,” said Dr. Kaplan, head of the pediatric infectious disease section at Baylor College of Medicine and chief of the infectious disease service at Texas Children's Hospital, both in Houston.

At Le Bonheur Children's Medical Center in Memphis, the rate of acute osteoarticular infections increased from 2.6 to 6.0 per 1,000 admissions between 2000 and 2004. The proportion of those infections caused by MSSA remained constant at 10%–13%, but those caused by MRSA rose from 4% to 40%. Moreover, 71% of the patients with MRSA had subperiosteal abscesses, compared with 38% of those with MSSA, and surgical procedures were required in 91% with MRSA versus 62% with MSSA (J. Pediatr. Orthop. 2006;26:701–2). Similar findings have been reported elsewhere, Dr. Kaplan noted.

Recent studies have shown that osteomyelitis caused by PVL-positive S. aureus strains was associated with more severe local disease and a greater systemic inflammatory response, compared with osteomyelitis caused by S. aureus not containing that gene (Pediatrics 2006;117:433–40), and that PVL-positive isolates were associated with an increased likelihood of complications in children with osteomyelitis (Pediatr. Infect. Dis. J. 2005;24:284–5).

MRI appears to be the optimal method for detection of osteomyelitis resulting from community-acquired S. aureus.

In a retrospective study by Dr. Kaplan and his associates of 199 such children seen between August 2001 and December 2006, MRI had a sensitivity of 98% for diagnosing the infection, compared with a 53% sensitivity with bone scintigraphy. Of 36 patients who had both imaging studies done, results were discordant in 17 cases. In all of those, the MRI diagnosis proved to be the correct one (Pediatr. Radiol. 2008;38:841–7).

The study also showed that MRI—but not bone scan—allowed for visualization of extraosseous complications, including subperiosteal abscesses in 77 patients, pyomyositis in 43, septic arthritis in 31, and deep vein thrombosis in 12. “Clearly, MRI was superior to bone scan in detecting bone infection. In our institution, MRI is the first thing we use. It can help pick up other areas of concern,” Dr. Kaplan noted.

Some of these extraosseous complications also appear to be on the rise. At least two recent reports have documented cases of venous thrombophlebitis among children with invasive S. aureus infections. At Children's Medical Center in Dallas, 10 of 35 children with confirmed osteomyelitis developed deep vein thrombosis during the acute infection, with evidence of dissemination in six (J. Pediatr. 2006;149:537–41).

And at Texas Children's, Dr. Kaplan and his associates reported on 9 children seen between 1999 and 2004 who had venous thrombosis adjacent to the site of staphylococcal osteomyelitis. Seven patients had community-acquired infections caused by MRSA belonging to the same USA300 clonal group, and all 7 carried PVL genes. The USA300 clone may “have a unique propensity to cause [venous thrombosis] in association with osteomyelitis,” they concluded (Pediatrics 2006;117:1673–9).

Since then, they've seen about 40–50 children with osteomyelitis who developed thrombosis, despite not having genetic prothrombotic conditions. “We don't understand what's going on. There's clearly something different about these community isolates, especially the USA300 strain,” Dr. Kaplan commented.

The USA300 MRSA genotype has also been implicated in septic arthritis. Among 44 isolates taken from 45 patients at Texas Children's with septic arthritis caused by S. aureus, 16 were MRSA; of these, 13 were USA300 and 14 were PVL-positive. Infections caused by USA300 were more likely to be associated with a longer duration of fever, bacteremia, and a C-reactive protein level of 10 mg/dL or greater (Pediatr. Infect. Dis. J. 2009;28:1076–80).

Rates of pyomyositis and myositis also have been on the rise at Texas Children's, and can be correlated to the emergence of CA-MRSA. Among 45 previously healthy children with bacterial pyomyositis or myositis, the cause was S. aureus in 58%. Of 24 community-acquired S. aureus isolates that were available, 15 were MRSA and 9 were MSSA. A total of 16 (including all the MRSA) isolates were found to be USA300, and 17 carried the PVL genes. The presence of MRSA, USA300, and/or the PVL genes was associated with a greater requirement for drainage procedures (Clin. Infect. Dis. 2006;43:953–60).

“Infection of muscles is something we just never saw in the past,” Dr. Kaplan commented.

Pulmonary manifestations are another increasingly common complication of CA-MRSA. An investigation of 70 children with invasive staphylococcal infections at Texas Children's between 2001 and 2004 showed that 47 had MRSA. Compared with 10 who had MSSA, those with MRSA were more likely to have pneumonia, empyema, lung abscess, and atelectasis. The presence of PVL was associated with abnormal chest image findings in patients with secondary pneumonia (Clin. Infect. Dis. 2005;41:583–90).

Influenza complicated by staph infections also is becoming more common, with most of these cases attributable to MRSA. In a study by the Centers for Disease Control and Prevention comparing pediatric deaths during three influenza seasons, bacterial coinfection rose substantially, from 6% in 2004–2005 to 15% in 2005–2006 to 34% in 2006–2007. Isolation of S. aureus from a sterile site rose from just 1 case in 2004–2005 to 22 in 2006–2007, of which two-thirds were MRSA. Children with staph coinfection were significantly older and more likely to have pneumonia and acute respiratory distress syndrome than those not coinfected (Pediatrics 2008;122:805–11).

Severe staphylococcal infections also are emerging along with CA-MRSA. In a descriptive report of 14 previously healthy adolescents with severe community-acquired S. aureus infections admitted to intensive care at Texas Children's with coagulopathy and sepsis, 12 were found to have MRSA and 2 had MSSA. Thirteen also had pulmonary involvement and/or bone and joint infection, four developed vascular complications, and three died. All isolates were identical or closely related to the USA300 clone (Pediatrics 2005;115:642–8).

The typical patient is an adolescent, usually with some trauma to an extremity, who may have underlying osteomyelitis and may develop pulmonary manifestations, and then becomes very ill. “We've now had seven deaths due to S. aureus sepsis in otherwise completely healthy children,” Dr. Kaplan said.

Disclosures: Dr. Kaplan has received research grants from Pfizer and Cubist Pharmaceuticals.

Severe CA-MRSA infections such as osteomyelitis (above, with subperiosteal abscess and soft tissue inflammation) have a high risk of complications.

Source Images courtesy Sheldon L. Kaplan

BETHESDA, MD. — Invasive infections in children caused by community-acquired methicillin-resistant Staphylococcus aureus are on the rise.

Though still far less common than simple skin and soft tissue CA-MRSA infections, increasing reports of serious infections such as osteomyelitis, bacteremia, and pneumonia have been raising concern in recent years. The increase appears to be related at least in part to the emergence of the “USA300” S. aureus clone containing the Panton-Valentine leukocidin (PVL) genes, Dr. Sheldon L. Kaplan said at the annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.

Rates of severe infection have been rising as MRSA has become more common in the community. Recommendations from the American Academy of Pediatrics state that in areas where MRSA accounts for 10% or more of CA-MRSA isolates, initial empiric therapy of severe infections that could be due to S. aureus should include vancomycin. Naficillin should also be included because it's superior to vancomycin for treating methicillin-sensitive S. aureus (MSSA).

Use of clindamycin should be based on local susceptibility. “You need to know the clindamycin susceptibility of CA-MRSA isolates in your area,” said Dr. Kaplan, head of the pediatric infectious disease section at Baylor College of Medicine and chief of the infectious disease service at Texas Children's Hospital, both in Houston.

At Le Bonheur Children's Medical Center in Memphis, the rate of acute osteoarticular infections increased from 2.6 to 6.0 per 1,000 admissions between 2000 and 2004. The proportion of those infections caused by MSSA remained constant at 10%–13%, but those caused by MRSA rose from 4% to 40%. Moreover, 71% of the patients with MRSA had subperiosteal abscesses, compared with 38% of those with MSSA, and surgical procedures were required in 91% with MRSA versus 62% with MSSA (J. Pediatr. Orthop. 2006;26:701–2). Similar findings have been reported elsewhere, Dr. Kaplan noted.

Recent studies have shown that osteomyelitis caused by PVL-positive S. aureus strains was associated with more severe local disease and a greater systemic inflammatory response, compared with osteomyelitis caused by S. aureus not containing that gene (Pediatrics 2006;117:433–40), and that PVL-positive isolates were associated with an increased likelihood of complications in children with osteomyelitis (Pediatr. Infect. Dis. J. 2005;24:284–5).

MRI appears to be the optimal method for detection of osteomyelitis resulting from community-acquired S. aureus.

In a retrospective study by Dr. Kaplan and his associates of 199 such children seen between August 2001 and December 2006, MRI had a sensitivity of 98% for diagnosing the infection, compared with a 53% sensitivity with bone scintigraphy. Of 36 patients who had both imaging studies done, results were discordant in 17 cases. In all of those, the MRI diagnosis proved to be the correct one (Pediatr. Radiol. 2008;38:841–7).

The study also showed that MRI—but not bone scan—allowed for visualization of extraosseous complications, including subperiosteal abscesses in 77 patients, pyomyositis in 43, septic arthritis in 31, and deep vein thrombosis in 12. “Clearly, MRI was superior to bone scan in detecting bone infection. In our institution, MRI is the first thing we use. It can help pick up other areas of concern,” Dr. Kaplan noted.

Some of these extraosseous complications also appear to be on the rise. At least two recent reports have documented cases of venous thrombophlebitis among children with invasive S. aureus infections. At Children's Medical Center in Dallas, 10 of 35 children with confirmed osteomyelitis developed deep vein thrombosis during the acute infection, with evidence of dissemination in six (J. Pediatr. 2006;149:537–41).

And at Texas Children's, Dr. Kaplan and his associates reported on 9 children seen between 1999 and 2004 who had venous thrombosis adjacent to the site of staphylococcal osteomyelitis. Seven patients had community-acquired infections caused by MRSA belonging to the same USA300 clonal group, and all 7 carried PVL genes. The USA300 clone may “have a unique propensity to cause [venous thrombosis] in association with osteomyelitis,” they concluded (Pediatrics 2006;117:1673–9).

Since then, they've seen about 40–50 children with osteomyelitis who developed thrombosis, despite not having genetic prothrombotic conditions. “We don't understand what's going on. There's clearly something different about these community isolates, especially the USA300 strain,” Dr. Kaplan commented.

The USA300 MRSA genotype has also been implicated in septic arthritis. Among 44 isolates taken from 45 patients at Texas Children's with septic arthritis caused by S. aureus, 16 were MRSA; of these, 13 were USA300 and 14 were PVL-positive. Infections caused by USA300 were more likely to be associated with a longer duration of fever, bacteremia, and a C-reactive protein level of 10 mg/dL or greater (Pediatr. Infect. Dis. J. 2009;28:1076–80).

Rates of pyomyositis and myositis also have been on the rise at Texas Children's, and can be correlated to the emergence of CA-MRSA. Among 45 previously healthy children with bacterial pyomyositis or myositis, the cause was S. aureus in 58%. Of 24 community-acquired S. aureus isolates that were available, 15 were MRSA and 9 were MSSA. A total of 16 (including all the MRSA) isolates were found to be USA300, and 17 carried the PVL genes. The presence of MRSA, USA300, and/or the PVL genes was associated with a greater requirement for drainage procedures (Clin. Infect. Dis. 2006;43:953–60).

“Infection of muscles is something we just never saw in the past,” Dr. Kaplan commented.

Pulmonary manifestations are another increasingly common complication of CA-MRSA. An investigation of 70 children with invasive staphylococcal infections at Texas Children's between 2001 and 2004 showed that 47 had MRSA. Compared with 10 who had MSSA, those with MRSA were more likely to have pneumonia, empyema, lung abscess, and atelectasis. The presence of PVL was associated with abnormal chest image findings in patients with secondary pneumonia (Clin. Infect. Dis. 2005;41:583–90).

Influenza complicated by staph infections also is becoming more common, with most of these cases attributable to MRSA. In a study by the Centers for Disease Control and Prevention comparing pediatric deaths during three influenza seasons, bacterial coinfection rose substantially, from 6% in 2004–2005 to 15% in 2005–2006 to 34% in 2006–2007. Isolation of S. aureus from a sterile site rose from just 1 case in 2004–2005 to 22 in 2006–2007, of which two-thirds were MRSA. Children with staph coinfection were significantly older and more likely to have pneumonia and acute respiratory distress syndrome than those not coinfected (Pediatrics 2008;122:805–11).

Severe staphylococcal infections also are emerging along with CA-MRSA. In a descriptive report of 14 previously healthy adolescents with severe community-acquired S. aureus infections admitted to intensive care at Texas Children's with coagulopathy and sepsis, 12 were found to have MRSA and 2 had MSSA. Thirteen also had pulmonary involvement and/or bone and joint infection, four developed vascular complications, and three died. All isolates were identical or closely related to the USA300 clone (Pediatrics 2005;115:642–8).

The typical patient is an adolescent, usually with some trauma to an extremity, who may have underlying osteomyelitis and may develop pulmonary manifestations, and then becomes very ill. “We've now had seven deaths due to S. aureus sepsis in otherwise completely healthy children,” Dr. Kaplan said.

Disclosures: Dr. Kaplan has received research grants from Pfizer and Cubist Pharmaceuticals.

Severe CA-MRSA infections such as osteomyelitis (above, with subperiosteal abscess and soft tissue inflammation) have a high risk of complications.

Source Images courtesy Sheldon L. Kaplan

BETHESDA, MD. — Invasive infections in children caused by community-acquired methicillin-resistant Staphylococcus aureus are on the rise.

Though still far less common than simple skin and soft tissue CA-MRSA infections, increasing reports of serious infections such as osteomyelitis, bacteremia, and pneumonia have been raising concern in recent years. The increase appears to be related at least in part to the emergence of the “USA300” S. aureus clone containing the Panton-Valentine leukocidin (PVL) genes, Dr. Sheldon L. Kaplan said at the annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.

Rates of severe infection have been rising as MRSA has become more common in the community. Recommendations from the American Academy of Pediatrics state that in areas where MRSA accounts for 10% or more of CA-MRSA isolates, initial empiric therapy of severe infections that could be due to S. aureus should include vancomycin. Naficillin should also be included because it's superior to vancomycin for treating methicillin-sensitive S. aureus (MSSA).

Use of clindamycin should be based on local susceptibility. “You need to know the clindamycin susceptibility of CA-MRSA isolates in your area,” said Dr. Kaplan, head of the pediatric infectious disease section at Baylor College of Medicine and chief of the infectious disease service at Texas Children's Hospital, both in Houston.

At Le Bonheur Children's Medical Center in Memphis, the rate of acute osteoarticular infections increased from 2.6 to 6.0 per 1,000 admissions between 2000 and 2004. The proportion of those infections caused by MSSA remained constant at 10%–13%, but those caused by MRSA rose from 4% to 40%. Moreover, 71% of the patients with MRSA had subperiosteal abscesses, compared with 38% of those with MSSA, and surgical procedures were required in 91% with MRSA versus 62% with MSSA (J. Pediatr. Orthop. 2006;26:701–2). Similar findings have been reported elsewhere, Dr. Kaplan noted.

Recent studies have shown that osteomyelitis caused by PVL-positive S. aureus strains was associated with more severe local disease and a greater systemic inflammatory response, compared with osteomyelitis caused by S. aureus not containing that gene (Pediatrics 2006;117:433–40), and that PVL-positive isolates were associated with an increased likelihood of complications in children with osteomyelitis (Pediatr. Infect. Dis. J. 2005;24:284–5).

MRI appears to be the optimal method for detection of osteomyelitis resulting from community-acquired S. aureus.

In a retrospective study by Dr. Kaplan and his associates of 199 such children seen between August 2001 and December 2006, MRI had a sensitivity of 98% for diagnosing the infection, compared with a 53% sensitivity with bone scintigraphy. Of 36 patients who had both imaging studies done, results were discordant in 17 cases. In all of those, the MRI diagnosis proved to be the correct one (Pediatr. Radiol. 2008;38:841–7).

The study also showed that MRI—but not bone scan—allowed for visualization of extraosseous complications, including subperiosteal abscesses in 77 patients, pyomyositis in 43, septic arthritis in 31, and deep vein thrombosis in 12. “Clearly, MRI was superior to bone scan in detecting bone infection. In our institution, MRI is the first thing we use. It can help pick up other areas of concern,” Dr. Kaplan noted.

Some of these extraosseous complications also appear to be on the rise. At least two recent reports have documented cases of venous thrombophlebitis among children with invasive S. aureus infections. At Children's Medical Center in Dallas, 10 of 35 children with confirmed osteomyelitis developed deep vein thrombosis during the acute infection, with evidence of dissemination in six (J. Pediatr. 2006;149:537–41).

And at Texas Children's, Dr. Kaplan and his associates reported on 9 children seen between 1999 and 2004 who had venous thrombosis adjacent to the site of staphylococcal osteomyelitis. Seven patients had community-acquired infections caused by MRSA belonging to the same USA300 clonal group, and all 7 carried PVL genes. The USA300 clone may “have a unique propensity to cause [venous thrombosis] in association with osteomyelitis,” they concluded (Pediatrics 2006;117:1673–9).

Since then, they've seen about 40–50 children with osteomyelitis who developed thrombosis, despite not having genetic prothrombotic conditions. “We don't understand what's going on. There's clearly something different about these community isolates, especially the USA300 strain,” Dr. Kaplan commented.

The USA300 MRSA genotype has also been implicated in septic arthritis. Among 44 isolates taken from 45 patients at Texas Children's with septic arthritis caused by S. aureus, 16 were MRSA; of these, 13 were USA300 and 14 were PVL-positive. Infections caused by USA300 were more likely to be associated with a longer duration of fever, bacteremia, and a C-reactive protein level of 10 mg/dL or greater (Pediatr. Infect. Dis. J. 2009;28:1076–80).

Rates of pyomyositis and myositis also have been on the rise at Texas Children's, and can be correlated to the emergence of CA-MRSA. Among 45 previously healthy children with bacterial pyomyositis or myositis, the cause was S. aureus in 58%. Of 24 community-acquired S. aureus isolates that were available, 15 were MRSA and 9 were MSSA. A total of 16 (including all the MRSA) isolates were found to be USA300, and 17 carried the PVL genes. The presence of MRSA, USA300, and/or the PVL genes was associated with a greater requirement for drainage procedures (Clin. Infect. Dis. 2006;43:953–60).

“Infection of muscles is something we just never saw in the past,” Dr. Kaplan commented.

Pulmonary manifestations are another increasingly common complication of CA-MRSA. An investigation of 70 children with invasive staphylococcal infections at Texas Children's between 2001 and 2004 showed that 47 had MRSA. Compared with 10 who had MSSA, those with MRSA were more likely to have pneumonia, empyema, lung abscess, and atelectasis. The presence of PVL was associated with abnormal chest image findings in patients with secondary pneumonia (Clin. Infect. Dis. 2005;41:583–90).

Influenza complicated by staph infections also is becoming more common, with most of these cases attributable to MRSA. In a study by the Centers for Disease Control and Prevention comparing pediatric deaths during three influenza seasons, bacterial coinfection rose substantially, from 6% in 2004–2005 to 15% in 2005–2006 to 34% in 2006–2007. Isolation of S. aureus from a sterile site rose from just 1 case in 2004–2005 to 22 in 2006–2007, of which two-thirds were MRSA. Children with staph coinfection were significantly older and more likely to have pneumonia and acute respiratory distress syndrome than those not coinfected (Pediatrics 2008;122:805–11).

Severe staphylococcal infections also are emerging along with CA-MRSA. In a descriptive report of 14 previously healthy adolescents with severe community-acquired S. aureus infections admitted to intensive care at Texas Children's with coagulopathy and sepsis, 12 were found to have MRSA and 2 had MSSA. Thirteen also had pulmonary involvement and/or bone and joint infection, four developed vascular complications, and three died. All isolates were identical or closely related to the USA300 clone (Pediatrics 2005;115:642–8).

The typical patient is an adolescent, usually with some trauma to an extremity, who may have underlying osteomyelitis and may develop pulmonary manifestations, and then becomes very ill. “We've now had seven deaths due to S. aureus sepsis in otherwise completely healthy children,” Dr. Kaplan said.

Disclosures: Dr. Kaplan has received research grants from Pfizer and Cubist Pharmaceuticals.

Severe CA-MRSA infections such as osteomyelitis (above, with subperiosteal abscess and soft tissue inflammation) have a high risk of complications.

Source Images courtesy Sheldon L. Kaplan