Emergence of azithromycin-resistant extensively drug-resistant Salmonella Kentucky ST314 in Taiwan.

Salmonella enterica serovar Kentucky (S. Kentucky) has emerged globally as a multidrug-resistant lineage but has historically been rare in Taiwan. Here, we report a recent surge of azithromycin-resistant extensively drug-resistant (AziR-XDR) S. Kentucky identified through nationwide surveillance from 2004 to 2025. Among 45,223 Salmonella isolates from humans, 192 (0.42%) were identified as S. Kentucky, with a marked increase observed in 2024─2025. Whole-genome sequencing of 165 isolates recovered from humans, animals, and chicken meat identified three major sequence types (ST314, ST198, and ST152), with ST314 accounting for 86.1% of the isolates. Thirty-two isolates were classified as AziR-XDR, including 28 ST314 and 4 ST198 isolates. Phylogenetic analysis revealed a dominant ST314 lineage carrying a conserved chromosomal multiple resistance region harboring aadA1, aph(3')-Ia, bla TEM-1, dfrA5, floR, sul3, and tet(A) together with a gyrA_D87G mutation. AziR-XDR isolates arose when strains from this lineage further acquired a non-mobilizable IncFIB(pB171) plasmid carrying bla DHA-1, mph(A), qnrB, and sul1. The observed phylogenetic diversity of ST314 isolates, together with structural variation in the IncFIB(pB171) plasmids, suggests that this resistance architecture had diversified before its introduction into Taiwan. In the NCBI Pathogen Detection database, the complete AziR-XDR resistance configuration has been observed only among Taiwanese ST314 isolates to date. Genomic comparisons further indicated close genetic relatedness between Taiwanese isolates and strains circulating in China and internationally. In contrast, ST198 AziR-XDR isolates were embedded within broader international lineages. These findings indicate that the recent increase of AziR-XDR ST314 in Taiwan is driven by a lineage carrying a pre-assembled resistance architecture and highlight the importance of genomic surveillance in tracking the emergence and dissemination of high-risk resistant clones.