Azithromycin Resistance in Salmonella Typhi and Paratyphi Across South Asia: A Systematic Review and Meta-Analysis

Azithromycin is a frontline oral treatment for uncomplicated enteric fever in South Asia; however, emerging resistance in Salmonella enterica serovars Typhi and Paratyphi challenges its long-term efficacy. We conducted a PRISMA-compliant systematic review and meta-analysis, searching 6 databases to estimate the prevalence of azithromycin resistance in low-income and developing countries in South Asia. Accepted resistance classifications were based on interpretive criteria used by individual study authors, acknowledging that the Clinical and Laboratory Standards Institute breakpoints for S. Typhi were introduced in 2015 and that no official breakpoints exist for S. Paratyphi. From 1863 screened records, 74 studies comprising 30 085 isolates were analyzed using random-effects models. The pooled azithromycin resistance was 5% (95% CI: 4%-5%) for S. Typhi and 5% (95% CI: 0%-9%) for S. Paratyphi. When both serotypes were combined, the overall prevalence was 9% (95% CI: 3%-14%). Subgroup analysis revealed significant geographical heterogeneity: Pakistan and India reported the highest prevalence (8% and 7%, respectively), while Nepal and Bangladesh remained at 1%. Meta-regression did not detect a statistically significant temporal trend from 2005 to 2024. Although overall resistance remains relatively low, high prevalence in specific regions necessitates rigorous antimicrobial stewardship and enhanced surveillance to preserve azithromycin's clinical utility against enteric fever in South Asia.