Narrow-spectrum, compared with broad-spectrum, antibiotics equally effective with less adverse events

Abstract

Gerber JS, Ross RK, Bryan M, Localio AR, Szymczak JE, Wasserman R, et al. Association of Broad- vs Narrow-Spectrum Antibiotics With Treatment Failure, Adverse Events, and Quality of Life in Children With Acute Respiratory Tract Infections. JAMA 2017;318:2325-36. Question Among children with acute respiratory infections (acute otitis media, group A streptococcal pharyngitis, and acute sinusitis), what is the efficacy and safety profile of broad-spectrum, compared with narrow-spectrum, antibiotics? Design Retrospective and prospective cohorts. Stratified and propensity score-matched analyses. Setting Thirty-one pediatric practices in Pennsylvania and New Jersey. Participants Children 6 months to 12 years, with acute otitis media, group A streptococcal pharyngitis, and acute sinusitis. Intervention Broad- versus narrow-spectrum antibiotics. Outcomes Effectiveness and adverse events. Main Results Broad-spectrum antibiotics were not associated with less treatment failure, risk difference 0.3% (95% CI, −0.4% to 0.9%), and were associated with more clinician-reported and patient-reported adverse events, risk difference 1.1% (95% CI, 0.4% to 1.8%) and 12.2% (95% CI, 7.3% to 17.2%), respectively. Conclusions Narrow-, compared with broad-spectrum antibiotics were equally effective and demonstrated a lower rate of adverse events. Commentary This cohort study supports guidelines recommending narrow-spectrum amoxicillin or penicillin for treatment of acute otitis media, acute sinusitis, and group A streptococcal pharyngitis in children. Although broad-spectrum antibiotics, such as amoxicillin-clavulanate, are commonly prescribed based on conflicting guidelines for these conditions, they were not associated with improved outcomes compared to narrow-spectrum therapy. This large retrospective cohort demonstrated convincingly that broad-spectrum antibiotics do not lower overall rates of treatment failure, even when adjusting for differences in provider prescribing practices or illness severity using clinician-stratified and propensity-score matched analyses. The unique inclusion of patient-reported outcomes in a prospective cohort detected a 10-fold higher rate of adverse events compared with the retrospective cohort, which suggests most antibiotic adverse events are unreported and/or unrecognized by clinicians. Also, in this group, broad-spectrum antibiotics were associated with an increased risk of adverse events with no improvement in quality of life. While observational cohorts undoubtedly include children with viral infections that may obfuscate differences in antibiotic efficacy, this study reflects real clinical practice where the empiric choice of broad rather than narrow-spectrum antibiotics for acute respiratory infections in children may lead to more harm than benefit.