Genomic Insights Into Spatiotemporal Dynamics of Acquired Azithromycin Resistance Genes in <i>Salmonella</i> Strains Worldwide

ABSTRACT Azithromycin has been used for clinical invasive infections caused by fluoroquinolone‐ and third‐generation cephalosporin‐resistant Salmonella , and mass drug administration with azithromycin has been used to reduce under‐5 mortality in children in some countries. However, our understanding of the global distribution and temporal trends of azithromycin‐resistant Salmonella remains insufficient. Here, we analyzed 260,195 genomes with clear metadata to uncover the global distribution and spatiotemporal trends of acquired azithromycin resistance genes in Salmonella worldwide. In silico analysis revealed that 1.28% of 260,195 Salmonella strains carried at least one azithromycin resistance gene. Overall, the mph(A) gene was the dominant cause of azithromycin resistance, and increasing trends of mph(A) in humans, aquatic animals, food, wild animals, and environmental samples were observed, especially in serovars S . Newport and S . I 1,4,[5],12:i:‐ from Asia, Europe, and South America. In addition, co‐occurrence of mph(A) ‐positive strains with last‐line antibiotic resistance genes, for example, bla NDM , mcr , and tet(X4) , was observed. Phylogenetic analysis showed acrB p. R717L was mainly observed in S . Typhimurium ST19 from humans and pigs in China, and acrB p. R717L was mainly observed in human‐derived S . Enteritidis ST11 strains from the United Kingdom. Azithromycin‐resistant Salmonella showed an obvious increasing trend at the global level. In summary, this study presents a comprehensive atlas of acquired azithromycin resistance genes in global Salmonella strains, which provides valuable insights for understanding the transmission dynamics of azithromycin‐resistant Salmonella .