Optimal Duration of Antibiotic Treatment for Group A Streptococcal Pharyngitis in Children: A Systematic Review and Dose-Response Meta-Analysis

Background: Group A streptococcal (GAS) pharyngitis drives substantial antibiotic prescribing in children. The 10-day standard burdens adherence and prolongs exposure, increasing selective pressure for resistance. Yet, whether shorter courses achieve comparable outcomes remains unresolved. Purpose: To address how the duration of oral antibiotics affects clinical outcomes in children and adolescents with suspected or confirmed GAS pharyngitis. Data Sources: MEDLINE, Embase, CENTRAL, Web of Science, and CINAHL from inception to July 2025. Reviewers also searched reference lists of eligible trials and relevant systematic reviews. Study Selection: Randomized trials enrolling children and adolescents [≤]18 years with suspected or confirmed GAS pharyngitis comparing different durations of oral antibiotics, or oral antibiotics against placebo or no treatment. Data Extraction: Paired reviewers independently screened records, extracted data, and assessed risk of bias. Data Synthesis: We performed random-effects dose-response meta-analyses with restricted cubic splines and rated the certainty of evidence using GRADE. Forty-five trials enrolling 22,636 participants met eligibility criteria. Across outcomes, low to moderate certainty evidence suggests that 3, 5, and 10 days of antibiotic treatment may produce little to no difference. Moderate certainty evidence supports similar effects of 5 and 10 days on clinical cure, relapse, and adverse events. Evidence comparing 3 and 10 days carries lower certainty. Serious adverse events were rare: no deaths, 4 cases of acute rheumatic fever, and 4 cases of post-streptococcal glomerulonephritis among 776, 8,818, and 9,096 participants, respectively, making clinically important differences across treatment durations unlikely. Limitations: Evidence on 3-day courses came almost exclusively from trials of azithromycin, limiting inference about shorter penicillin regimens. Findings apply most directly to high-income settings. Conclusion: These findings challenge the long-standing 10-day standard for pediatric GAS pharyngitis and show that 5 days of oral antibiotics are likely as effective and safe as 10 days.