Transmission dynamics of ST346 carbapenem-resistant Providencia huaxiensis carrying blaNDM-1 and/or blaKPC-2 during the COVID-19 pandemic

Carbapenem-resistant <i>Providencia</i> spp. (CRPs) isolates are increasing, posing severe therapeutic challenges. Here, we analyzed 46 CRP isolates carrying <i>bla</i> _NDM-1 and/or <i>bla</i> _KPC-2 from patients (<i>n</i> = 40) with 60% demonstrating clinical infections and clinical environment samples (<i>n</i> = 6). 33 <i>Providencia huaxiensis</i> strains were identified, with ST346 (93.9%, 31/33) being the predominant sequence type. Transmission dynamics analysis identified that Cluster I (<i>n</i> = 12, SNPs≤36) linking to non-transferable pCTX-<i>M</i>-NDM-<i>repM</i> plasmids, replaced Cluster III (<i>n</i> = 13, SNPs<25), which harbored both IncT_NDM-<i>repM</i> (conjugation frequency: 5.04E-2; a fitness cost of 17.31%-19.41% with <i>p</i> < 0.0001) and pCTX-M plasmids. Notably, we identified 9 (29.0%, 9/31) ST346 isolates co-producing KPC-2 and NDM-1 and tracked the evolution of this phenomenon. Bayesian Skyline analysis indicated a 120% expansion of the ST346 clone during 2020-2022, in contrast to the decline in the cross-host ST4 clone (80% reduction). Our study tracks and alerts to the emergence of a hospital-acquired ST346 CR-<i>P. huaxiensis</i> clone with multidrug resistance, hypervirulent phenotype, and elevated transmission risk.