Antimicrobial Resistance Burden of Non-Typhoidal Salmonella Across Human, Swine and Poultry Sources in Southern Vietnam, 2012–2021

We investigated an archived collection of 373 non-typhoidal Salmonella (NTS) isolates (2012–2021) from human clinical cases (n = 99), pork (n = 140), live farm pigs (n = 51), broiler meat (n = 42), and live farm broilers (n = 41) in southern Vietnam using phenotypic and PCR screening and whole-genome sequencing (WGS) of 60 multidrug-resistant (MDR) strains. Overall MDR frequency was 71.6% (267/373). Poultry isolates exhibited the highest resistance burden (MDR >95%), primarily mediated by chromosomal fluoroquinolone mutations (e.g., Salmonella Indiana ST17 in live farm broilers) and plasmid-associated blaCTX-M-65 on IncFIB replicons in broiler meat Salmonella Infantis ST32 (ceftriaxone resistance: 64.3%). In contrast, live farm pigs (MDR 86.3%) were the primary reservoir for plasmid-borne determinants (qnrS1, mcr-1.1, mcr-3.1). From 2012–2016 (n = 13) to 2017–2021 (n = 20), swine colistin MIC90 rose from 2.0 to 16.0 µg/mL as mcr detection increased from 0.0% (0/13) to 35.0% (7/20). Overall, the 10-year live pig isolates maintained a colistin MIC90 of 8.0 µg/mL. Close genetic relatedness in monophasic S. Typhimurium ST34 (shared cgMLST clusters 17881 and 39194) between swine and humans supported potential zoonotic transmission. WGS reliably predicted cephalosporin (96.7% concordance, 93.3% sensitivity, 97.8% specificity) and tetracycline resistance (95.0% concordance). However, chromosomal markers missed most fluoroquinolone resistance (sensitivity: 32.7%) because resistance was plasmid-mediated (qnrS1). Combining chromosomal mutations with plasmid-mediated quinolone resistance (PMQR) genes increased sensitivity to 100.0% (concordance: 95.0%). Fluoroquinolone and colistin resistance mechanisms thus differed between poultry and swine production chains in southern Vietnam. Genomic surveillance in this region needs to screen both chromosomal mutations and plasmid-borne resistance genes alongside MIC testing.