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Macrolide antibiotics fail to provide additional benefit for children with pneumonia
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For children hospitalized with community-acquired pneumonia, there is no significant difference between treatment with beta-lactam monotherapy and beta-lactam plus macrolide combination therapy concerning length of stay, intensive care admission, rehospitalization or recovery at follow-up.
“Macrolide antibiotics possess in vitro activity against Mycoplasma pneumoniae and Chlamydophila pneumoniae, and the [IDSA] guideline recommends their use when such pathogens are suspected,” Derek J. Williams, MD, MPH, from the division of hospital medicine in Monroe Carell Jr. Children’s Hospital at Vanderbilt University Medical Center, and colleagues wrote. “However, with few clinical studies demonstrating the effectiveness of macrolides in children, the guideline grades this recommendation as weak.”
The researchers note that because macrolides are frequently used as empirical therapy for pediatric pneumonia, it is important that the benefits of macrolide therapy plus beta-lactam are established.
To evaluate the efficacy of beta-lactam monotherapy against beta-lactam plus macrolide combination therapy in children hospitalized with pneumonia, Williams and colleagues conducted a study that assessed data collected from the Etiology of Pneumonia in the Community Study. This study, which was multicenter, prospective and population based, included children hospitalized with community-acquired pneumonia between Jan. 1, 2010, and June 30, 2012.
All children were 18 years of age or younger and treated at three hospitals located in Nashville, Tennessee, Memphis, Tennessee, and Salt Lake City, Utah. Diagnoses were confirmed through X-ray studies, and all children were administered beta-lactam monotherapy or beta-lactam plus macrolide combination therapy.
Beta-lactam monotherapy was defined by the researchers as the exclusive use of oral or parenteral second- or third-generation cephalosporin, penicillin, ampicillin, ampicillin-sulbactam, amoxicillin or amoxicillin-clavulanate. This treatment was compared with the use of a beta-lactam plus an oral or parenteral macrolide, including azithromycin or clarithromycin. Length of stay for patients was assessed using multivariable Cox proportional hazards regression. Intensive care admission, rehospitalizations and self-reported recovery were also analyzed using logistic regression.
Of the 1,418 children included in the analysis, 693 were female and the median age was 27 months (interquartile range, 12 to 69 months). This cohort accounted for 60.1% of the children in the Etiology of Pneumonia in the Community Study with diagnoses confirmed by X-ray study. Most participants (71.9%) were administered beta-lactam monotherapy, and 28.1% were given beta-lactam plus macrolide combination therapy.
No significant difference in length of hospital stay was observed between the two groups (median, 55 vs. 59 hours; adjusted hazard ratio, 0.87; 95% CI, 0.74-1.01). When a propensity-matched cohort was used to compare length of stay, similar results were observed (n = 560, 39.5%). The researchers also observed no significant difference in intensive care admission, rehospitalizations and self-reported recovery.
“Judicious antibiotic selection is critical to slowing the progression of antimicrobial resistance, and excessive use of macrolides has been an important target,” Williams and colleagues wrote. “Despite overall declines in antibiotic use in U.S. outpatient children with acute respiratory illness between 2000 and 2010, the use of broad-spectrum antibiotics in this same population nearly doubled, largely as a result of increased use of macrolides.”
“Thus, clinicians must weigh the theoretical individual benefits of empirical macrolide therapy against the risk of adverse drug effects and the societal risks associated with antimicrobial resistance,” they continued. – by Katherine Bortz
Disclosure: The authors report no relevant financial disclosures.
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