Burden of antimicrobial resistance in culture-confirmed Salmonella Typhi isolates in India from 1977 to 2024: A systematic review and meta-analysis

Abstract

Background Antimicrobial-resistant (AMR) Salmonella Typhi (S. Typhi) is a persistent public health threat in India. We conducted a systematic review and meta-analysis to estimate the prevalence and temporal trends of AMR S. Typhi across Indian states to inform prevention and treatment strategies. Methods We systematically reviewed antimicrobial resistance in S. Typhi isolates from India, including studies published up to March 31, 2025, with no start-date restriction. We screened eligible articles from PubMed-MEDLINE, EMBASE, Scopus, Web of Science, and AMR surveillance networks and excluded studies on chronic carriers and travellers. We assessed risk of bias using the Risk Of Bias In Non-randomised Studies - of Exposures (ROBINS-E) tool. We conducted meta-analysis using a random-effects model to estimate the prevalence of multidrug resistance (MDR; resistance to chloramphenicol, ampicillin, and co-trimoxazole) and resistance to fluoroquinolones, third-generation cephalosporins, and azithromycin across five-year periods, Indian states, and age groups (<18 versus all ages). Results We analysed data from 188 of 4,430 identified studies. MDR declined from 65% (95% CI 63-67) in 1990-94 to nearly 0% (95% CI 0-1) >= 2020. Fluoroquinolone resistance rose from 2% (95% CI 1-2) in 1990-94-85% (95% CI 84-86) in 2015-19, then declined slightly, with similar trends in children but marked variation across Indian states. Resistance to third-generation cephalosporins, azithromycin, and carbapenems remained below 5%, 8%, and 2%, respectively. Our meta-analysis of studies with samples collected from 2015 onwards showed a pooled summary resistance estimate of 82% (95% CI 74-87) for fluoroquinolones, 3% (95% CI 2-4) for third-generation cephalosporins, and 3% (95% CI 1-6) for azithromycin. Conclusion Fluoroquinolone resistance in S. Typhi in India is high but is declining, while resistance to third-generation cephalosporins and azithromycin is low. As many isolates originated from major cities, caution is warranted when generalising nationally. Continued AMR surveillance is crucial to guide vaccination strategies and treatment decisions.