Abstract / Summary
Importance: Group A streptococcal (GAS) pharyngitis drives substantial morbidity and antibiotic prescribing in children. Ten days of antibiotics remains standard, although shorter courses could reduce treatment burdens, cumulative antibiotic exposure, and selective pressure for resistance. Whether shorter courses achieve comparable outcomes remains uncertain. Objective: To assess the effects of oral antibiotic treatment duration on clinical outcomes in children and adolescents with GAS pharyngitis. Data Sources MEDLINE, Embase, CENTRAL, Web of Science, and CINAHL from inception to July 2025, without language restrictions. Study Selection: Randomized trials of participants [≤]18 years with suspected or confirmed GAS pharyngitis comparing different durations of oral antibiotics, or oral antibiotics against placebo or no treatment. Data Extraction and Synthesis: Pairs of reviewers selected studies and extracted data. Random-effects dose-response meta-analysis summarized the effect of duration on outcomes. The GRADE approach guided judgments about the certainty of evidence. Main Outcomes and Measures: Clinical cure, relapse, adverse events, mortality, serious adverse events, acute rheumatic fever, purulent complications, and poststreptococcal glomerulonephritis. Results: Forty-five trials enrolling 22,636 participants met eligibility criteria. Moderate certainty evidence suggests little to no clinically important difference between 5 vs 10 days in clinical cure (14 fewer cures per 1000 [95% CI 27 fewer to 2 fewer]), relapse (5 fewer per 1000 [11 fewer to 3 more]), or adverse events (10 more per 1000 [6 fewer to 30 more]). Sensitivity analyses excluding macrolides produced similar results. Low certainty evidence also suggests little to no clinically important difference in clinical cure, relapse, or adverse events between 3 vs 10 days of treatment, but nearly all evidence came from trials of azithromycin, and these findings do not establish the effects of 3-day regimens of penicillins or other antibiotics. Serious adverse events were rare: no deaths and 4 cases of acute rheumatic fever among 776 and 8,818 participants, respectively, making clinically important differences across treatment durations unlikely. Conclusions and Relevance: For children at low risk of acute rheumatic fever, 5 days of oral antibiotics likely provides similar benefits and harms as 10 days while reducing treatment burden and antibiotic exposure. The effects of 3-day regimens remains uncertain. Funding: Canadian Institutes of Health Research (CIHR). Grant No. 540708