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CME Released: 11/17/2011
Valid for credit through: 11/17/2012
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The 2009 pandemic influenza A (pH1N1) virus was associated with high rates of hospitalization and death in children, and it continues to circulate worldwide. Studies to date have indicated pH1N1-related mortality rates in the pediatric intensive care unit ranging from 7% in Canada, Australia, and New Zealand to 39% in Argentina.
Because data are limited for children with pH1N1-related critical illness, it has been difficult to ascertain the roles of chronic conditions and bacterial coinfection in mortality. To evaluate critical illness among children during the 2009 H1N1 pandemic, the investigators established a large, multicenter registry of patients admitted to pediatric intensive care units in major US pediatric hospitals.
A significant number of previously healthy children developed severe pneumonia and respiratory failure when infected with pH1N1 influenza during the 2009 pandemic. A study published online November 7 in Pediatrics associates an 8-fold increased mortality rate among such children with coinfection by methicillin-resistant Staphylococcus aureus (MRSA).
The dual infection can establish a potentially lethal synergy as the viral assault compromises immunity and the bacterial infection destroys lung tissue. Without widespread vaccination, the situation could return because community-acquired MRSA in children is becoming more prevalent and pH1N1 is still in circulation.
Members of the Pediatric Acute Lung Injury and Sepsis Investigator's Network analyzed data from 838 children treated at 35 US pediatric intensive care units for probable pH1N1 influenza from April 2009 to April 2010. Median age was 6 years. Most patients were in respiratory failure, with 564 (67.3%) requiring mechanical ventilation and 33 (3.9%) receiving extracorporeal membrane oxygenation. Despite aggressive treatment and vancomycin use, 75 children (8.9%) died. Overall, 71 (8.5%) of the patients had presumed diagnosis of early S aureus infection of the lung, with 48% of those apparently being MRSA.
In their multivariate analysis the investigators controlled for demographics; pediatric intensive care unit admission, comorbidities, and coinfections; treatments; and secondary influenza-related complications such as encephalitis and myocarditis.
Of the 838 children, 587 had 1 or more chronic health conditions, including asthma, compromised immune deficiency, or a neurological disorder. Among the 251 previously healthy children, the only shared risk factor for those who died was MRSA lung infection (relative risk, 8; 95% confidence interval, 3.1 - 20.6; P < .0001). Of the 251 previously healthy children, 26 (10.4%) had S aureus lung infection, as did 8 of the 18 children who died (44%), 6 of whom were confirmed to have had MRSA. Most of the children receiving vancomycin did not survive.
Secondary conditions and MRSA infection may explain the high morbidity and mortality rates among children infected with pH1N1 in the study year, the investigators conclude. "There's more risk for MRSA to become invasive in the presence of flu or other viruses," first author Adrienne Randolph, MD, from Boston Children's Hospital in Massachusetts says in a news release. "These deaths in co-infected children are a warning sign."
In the study, 88.2% of the children received oseltamivir, but only 5.8% received it before hospital admission. Because of the speed with which either or both infections develop, the researchers advise immediately treating children presenting with severe lower respiratory tract diseases during influenza season with antivirals such as oseltamivir, as well as antibiotics, without waiting for laboratory confirmation of the infections. The researchers write that influenza vaccination is the most effective approach for minimizing morbidity and mortality in coinfected children, because an effective vaccine has not yet been developed for MRSA.
Limitations of the study include confirmation of pH1N1 in only 65% of cases, lack of systematic detection of additional respiratory pathogens, and bacterial infections masked by use of broad-spectrum antibiotics. The sampling was restricted to large pediatric facilities.
This study was supported by US National Institutes of Health, the Centers for Disease Control and Prevention, and the Department of Health and Human Services. The authors have disclosed no relevant financial relationships.
Pediatrics. Published online November 7, 2011. Abstract
