Comparative Effectiveness of β-lactams Vs Azithromycin for Treatment of Outpatient Pediatric Community-acquired Pneumonia

Abstract

BackgroundGuidelines recommend amoxicillin as first-line therapy for mild, community-acquired pneumonia (CAP) in healthy, immunized children because of its effectiveness against S. pneumoniae. However, macrolides, which have inferior anti-pneumococcal activity, are the most commonly prescribed class of antibiotics for outpatient CAP. We aimed to determine the comparative effectiveness of β-lactam vs. macrolide antibiotics for the treatment of CAP.MethodsWe conducted a retrospective cohort study in 31 pediatric primary care practices. Patients 3 months to 18 years of age with CAP diagnosed between January 1, 2009 and December 31, 2013 were identified by ICD-9-CM codes. Clinical data were abstracted electronically. Treatment failure was defined as change in antibiotic by the pediatrician, emergency department (ED) visit, or hospitalization for pneumonia in the 2 weeks following diagnosis. Multivariable logistic regression models including children prescribed monotherapy of amoxicillin, broad-spectrum β-lactam antibiotics, or macrolides were built to determine the association of each class with treatment failure, adjusting for clinical and demographic characteristics.ResultsOf 10,470 children who received antibiotics for pneumonia, 4252 (40.6%) received amoxicillin, 4459 (42.6%) received macrolides, and 1759 (16.8%) received broad-spectrum β-lactams. The groups differed by age category, proportion of black patients, insurance type, documented fever, ordering of a chest X-ray, and prior antibiotic exposure. Treatment failure occurred in 633 children (6.1%); 418 required a change in antibiotic by the pediatrician, 169 required an ED visit, and 47 required hospitalization. In the adjusted model, macrolide prescribing was associated with a decreased odds of treatment failure in children <5 years old (aOR = 0.52, 95% CI 0.34, 0.78) and in children ≥5 years old (aOR = 0.32, 95% CI 0.25, 0.41). In practices with the lowest macrolide use, this relationship persisted (OR 0.46; 95% CI 0.23, 0.92).ConclusionWhile rates of treatment failure in children diagnosed with CAP in the outpatient setting were low, macrolides were associated with a lower failure rate than treatment with β-lactams. This may be due to residual confounding by indication or changing epidemiology of outpatient pneumonia.Disclosures T. Zaoutis, Astellas: Consultant, Consulting fee; Merck: Grant Investigator, Research grant; nabriva: Consultant, Consulting fee.