Global trends and molecular epidemiology of Azithromycin-resistant Salmonella: A systematic review and meta-analysis

Salmonella infections pose a significant public health challenge, affecting both social and economic dimensions across various countries. Different animal species serve as reservoirs for Salmonella and contribute to drug resistance in human isolates. The improper use of antimicrobials in livestock, companion animals, and humans has led to the rise of multidrug-resistant (MDR), extensively drug-resistant (XDR), and azithromycin-resistant Salmonella serovars globally. This systematic review and meta-analysis aim to evaluate heterogeneity, estimate pooled proportions, and outline the molecular epidemiology of these resistant Salmonella serovars worldwide.

We analyzed data from 15,514 Salmonella isolates, focusing on their genetic and phenotypic characteristics. Our analysis included meta-analyses and frequency analyses based on the studies' geographical locations, the types of isolates, and potential biases. We employed a random-effects model, specifically the DerSimonian-Laird method, to evaluate heterogeneity and estimate pooled proportions. The result is presented as a proportion and confidence interval after the inverse of the Freeman-Tukey transformation; otherwise, all the calculations were made using the Freeman-Tukey double arcsine transformation.

The pooled prevalence of azithromycin resistance among Salmonella isolates was 9.12% (95% CI: 6.53-12.07). Among azithromycin-resistant isolates, multidrug-resistant (MDR) and extensively drug-resistant (XDR) serovars accounted for 31.10% (95% CI: 18.82-44.86) and 19.30% (95% CI: 6.90-35.75), respectively. Resistance mechanisms involved multiple genetic factors, including efflux pumps (mefA, acrB gene mutation), enzymatic phosphorylation (mphA), and class 1 integrons gene cassettes. Notably, resistance rates varied by region and serovar, with high prevalence in Southern Asia and Eastern Europe.

Azithromycin resistance in Salmonella is a growing global health concern, complicated by the presence of MDR and XDR strains and diverse resistance mechanisms. Urgent, coordinated efforts encompassing enhanced surveillance, antimicrobial stewardship, and research are critical to controlling resistance and preserving azithromycin's efficacy in treating invasive salmonellosis through a One Health approach. Additionally, addressing antimicrobial use in the agriculture and veterinary sectors is critical to safeguarding public health.

We conducted a systematic review and meta-analysis after registering the protocol with PROSPERO (CRD420251047985), following the MOOSE (Meta-Analysis of Observational Studies in Epidemiology) guidelines.