Clinical and genomic characterization of carbapenem-resistant Klebsiella pneumoniae with concurrent production of NDM and OXA-48-like carbapenemases in Southern California, 2016 - 2022

The aim of this study was to correlate clinical and genomic characteristics of CRKP co-producing NDM and OXA-48-like carbapenemases isolated from patients in Southern California since 2016. Whole-genome sequencing was performed on clinical isolates obtained from various sources including blood, abdominal fluid, wound, and urine. Genetic diversity was observed in these CRKP including ST-14, ST-16, ST-167, ST-437, ST-2096, and ST-2497 lineages. Phylogenetic analysis revealed two closely related clusters (ST-14 and ST-2497), with single nucleotide polymorphism (SNP) difference ranging from 0 to 36, suggesting a possible local spread of these CRKP. Significant antimicrobial resistance (AMR) genes were identified in these CRKP including blaNDM-1, blaNDM-5, blaOXA-232, blaOXA-181, blaCTX-M-15, armA, tet(A), and tet(D). Moreover, pColKP3-type and Inc-type plasmids known to harbor AMR genes were also detected in these isolates. Most patients infected with this rare type of CRKP died, although their severe comorbidities also played important roles in their demise. Our study highlighted the extremely limited treatment option and poor clinical outcome associated with these dual carbapenemases producing CRKP. Real-time genomic surveillance of these unusual and deadly CRKP can provide critical information for infection prevention and guiding treatment.