Rising threat of metallo-β-lactamase-producing Klebsiella oxytoca complex in Taiwan, 2013-2022

The emergence of metallo-beta-lactamases (MBLs) within the Klebsiella oxytoca complex (CRKO) poses a significant challenge in Taiwan, with so far incomplete characterization of species distribution and carbapenemase variants. This study aimed to elucidate the diversity, variants, and clinical presentations of CRKO isolates collected from 2013 to 2022.

We analyzed production of carbapenemases by the modified carbapenem inhibitory method (mCIM) and the NG test^TM CARBA-5. Confirmation of five common carbapenemases and multilocus sequence typing were determined by polymerase chain reaction and sequencing. Nanopore whole-genome sequencing was used for the species differentiation and plasmids analysis. We also evaluated the clinical characteristics of the CRKO-infected patients.

Three species were identified: K. michiganensis (n = 102), K. pasteurii (n = 13), and K. oxytoca (n = 3). A majority of isolates (91.5%, n = 108) harbored at least one MBL gene, including bla_VIM-1 (n = 56), bla_IMP-8 (n = 26), and bla_NDM-1 (n = 19), with six isolates carrying dual carbapenemase genes. The bla_NDM-1 and bla_IMP-8 genes were located on IncFII(Yp) and IncA/C2 plasmids, respectively. Notably, 34.7% of isolates carried kleboxymycin gene clusters (KGC). Using CLSI and EUCAST criteria, 92.4% and 82.4% of isolates, respectively, were susceptible to cefiderocol. Among 92 infected patients, the 30-day mortality rate was 21.7%, associated with female gender, higher Charlson Comorbidity Index, higher Pitt bacteremia scores, presence of bacteremia, and inversely associated with KGC.

The high prevalence of CRKO carrying MBLs and the recent surge of the ST27-bla_NDM-1 genotype, poses significant treatment challenges and underscores the urgent need for enhanced surveillance in Taiwan.