Emergence of multidrug resistance and genomic analysis of azithromycin-resistant non-typhoidal Salmonella from diverse sources in China, 2006-2018.

Azithromycin is commonly recommended for the treatment of invasive salmonellosis, although the emergence of azithromycin resistance has become a new public health issue, it was seldomly investigated in China. This study analyzed 1230 non-typhoidal Salmonella (NTS) isolates from diverse sources in China (2006-2018), identifying 101 azithromycin-resistant NTS isolated from chicken, pork and human with minimum inhibitory concentration (MIC) values of 32-64 μg/mL of azithromycin across seven serotypes, primarily ST17 S. Indiana (n = 68) and ST52 S. Blockley (n = 26). All azithromycin-resistant NTS isolates exhibited multidrug resistance pattern with 48 isolates exhibited resistance to nine antibiotic categories. Genomic analysis identified six kinds of distinct macrolide resistance genes in azithromycin-resistant NTS isolates: mph(A) (n = 94), mph(E)-msr(E) (n = 4), erm(42) (n = 2), erm(G) (n = 1) and erm(T) (n = 1). mph(A) (93.07 %) was most prevalent and found within the genetic environment mph(A)-mrx-mphR(A)-IS6100. No mutation associated with azithromycin resistance was discovered in the 23S rRNA gene, and 50S ribosomal protein L22 and L4 encoding sequences. A total of 22 distinct plasmid replicons were identified, with IncX1 being the most prevalent (58.42 %, 59/101). Notably, mph(A) gene in all ST52 S. Blockley strains (n = 26) were exclusively located on the chromosome. In contrast, mph(A) in other six serotypes, and erm(42), erm(T), mph(E)-msr(E) were predicted to be on plasmids. Specifically, the erm(T) gene was associated with IncQ1 plasmids. These findings underscore the necessity of continuous surveillance of azithromycin resistance in NTS across the food chain to better understand and mitigate its potential public health impact.