From Widespread Use to Loss of Effectiveness: The Consequences of Inappropriate Azithromycin Prescriptions During the COVID‐19 Pandemic—A Systematic Review and Meta‐Analysis

Objectives We are aimed at evaluating whether the widespread use of azithromycin during the COVID‐19 pandemic led to a significant increase in bacterial resistance compared with the prepandemic period and estimating the magnitude of this effect through a systematic review and meta‐analysis. Methods This systematic review followed the PRISMA 2020 guidelines and Cochrane Handbook (Page,2021). Observational studies published between 2015 and 2025 reporting azithromycin resistance before and after the COVID‐19 pandemic were identified. Odds ratios (ORs) were pooled using a random‐effects model. Methodological quality was assessed using the Newcastle–Ottawa scale. Results Eight studies met the eligibility criteria and were included in the quantitative synthesis. The meta‐analysis demonstrated a significant increase in azithromycin resistance in the postpandemic period, with a pooled OR of 2.71 (95% CI: 2.04–3.59). Substantial heterogeneity was observed ( I 2 = 73.5 % ), justifying the use of a random‐effects model. Conclusions The findings provide robust evidence that the excessive and largely empirical use of azithromycin during the COVID‐19 pandemic contributed to a global rise in bacterial resistance. Strengthening antimicrobial stewardship policies is essential to preserve the clinical effectiveness of macrolides during future public health emergencies.