Effect of antibiotic therapy versus no antibiotics on nonoperative management outcomes in uncomplicated appendicitis: A systematic review and meta-analysis

PURPOSE: Although antibiotics are a recognized alternative to appendectomy for uncomplicated appendicitis, their specific benefit over observation alone remains unclear. This systematic review and meta-analysis aimed to isolate the antibiotic effect by directly contrasting antibiotics with observation in patients receiving nonoperative management (NOM) for uncomplicated appendicitis. METHODS: We systematically searched PubMed, Embase (Ovid), the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, the International Clinical Trials Registry Platform, and the International Standard Randomized Controlled Trial Number Registry from inception to October 5, 2025, to identify randomized or quasi-randomized trials comparing antibiotics versus observation (no antibiotics) for NOM. We defined treatment success at 30 days as the primary endpoint. To assess the potential risk-of-bias (ROB), the Cochrane RoB 2 instrument was employed, while the overall certainty of our findings was determined through the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. RESULTS: Three trials involving 437 participants were included: two randomized controlled trials (RCTs) and one quasi-RCT. Analysis restricted to RCTs demonstrated no significant effect of antibiotics on initial treatment success (RR: 1.03, 95% CI: 0.92-1.15). Analysis across three studies showed no significant differences in recurrence (RR: 1.38, 95% CI: 0.68-2.80) or the need for appendectomy during follow-up (RR: 0.98, 95% CI: 0.66-1.47). Evidence certainty was low for the primary outcome and very low for secondary outcomes. CONCLUSION: Current evidence is insufficient to determine whether antibiotics provide additional benefit over observation for uncomplicated appendicitis. Larger, adequately powered trials are needed to establish the comparative effectiveness of these approaches.