PEDIATRICS Vol. 107 No. 5 May 2001, pp. 1108-1115
Invasive Group A Streptococcal Infection and Nonsteroidal Antiinflammatory Drug Use Among Children With Primary Varicella
Received Jun 29, 2000; accepted Oct 5, 2000.
, §, 
,, ¶,
From the * Slone Epidemiology Unit, School of Public Health,
Boston University School of Medicine, Brookline, Massachusetts;
Respiratory Diseases Branch, Division of Bacterial and Mycotic
Diseases, National Center for Infectious Diseases, Centers for Disease
Control and Prevention, Atlanta, Georgia; § Epidemic Intelligence
Service, Epidemiology Program Office, Centers for Disease Control and
Prevention, Atlanta, Georgia; Center for American Indian and Alaskan
Native Health, Johns Hopkins University School of Public Health,
Baltimore, Maryland; and the ¶ National Immunization Program, Centers
for Disease Control and Prevention, Atlanta, Georgia.
Objectives. To test the hypothesis that nonsteroidal antiinflammatory drug use increases the risk of necrotizing soft tissue infections and, secondarily, all invasive group A streptococcal (GAS) infections in children with primary varicella infection.
Methods. We conducted a prospective, multicenter case-control study among children <19 years old. Cases were children hospitalized with primary varicella complicated by invasive GAS infection or necrotizing soft tissue infection identified by a network of 45 pediatric infectious disease specialists located throughout the United States. Controls were children with uncomplicated primary varicella residing in the same communities as the cases. Data on medical history, clinical features of the varicella infection, signs and symptoms of infectious complications, and medication use were collected by structured telephone interviews. Univariate and multivariate matched odds ratios were calculated using conditional logistic regression.
Results. Between June 1996 and September 1998, 52 cases of invasive GAS infection, including 21 with necrotizing soft tissue infection, and 172 controls with uncomplicated primary varicella were enrolled. Risk of invasive GAS infection was increased among children who were nonwhite (multivariate odds ratio [OR] 3.8, 95% confidence interval [CI]: 1.4-11), living in low-income households (OR 5.1, 95% CI: 1.7-15), exposed to varicella at home (OR 6.4, 95% CI: 2.6-16), or had a persistent high fever (OR 9.6, 95% CI: 2.8-33). Antipyretic regimen was associated with several measures of varicella illness severity among the controls. The risk of necrotizing soft tissue infection was not associated with the use of ibuprofen before the development of signs or symptoms of this complication (OR 1.3, 95% CI: 0.33-5.3). Risk of any invasive GAS infection was increased among children who had received ibuprofen (OR 3.9, 95% CI: 1.3-12), but not acetaminophen (OR 1.2, 95% CI: 0.50-3.0). However, there was no evidence of increasing risk with increasing duration of ibuprofen use. Subgroup analyses revealed that the risk of invasive GAS infection was increased only among children who had received both acetaminophen and ibuprofen.
Conclusions. These data do not support the hypothesis that nonsteroidal antiinflammatory drugs, or ibuprofen in particular, increase the risk of necrotizing GAS infections. A statistically significant association was observed between nonnecrotizing invasive GAS infection and ibuprofen use; however, because of potential confounding, the meaning of this unexpected result is unclear. Nonetheless, these data suggest that parents use ibuprofen or ibuprofen together with acetaminophen to treat high fever and severe illness, which seems to identify children at high risk for invasive GAS infection. Key words: children, confounding, group A streptococcus, ibuprofen, necrotizing infection, NSAIDs, varicella.
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