Genomic Characterization of KPC-31 and OXA-181 Klebsiella pneumoniae Resistant to New Generation of β-Lactam/β-Lactamase Inhibitor Combinations

Abstract

Background: Carbapenem resistant Klebsiella pneumoniae (cr-Kp) causes serious infections associated with a high mortality rate. The clinical efficacy of ceftazidime/avibactam (CZA), meropenem/vaborbactam (M/V), and imipenem/relebactam (I/R) against cr-Kp is challenged by the emergence of resistant strains, making the investigation and monitoring of the main resistance mechanisms crucial. In this study, we reported the genome characterization of a Klebsiella pneumoniae strain isolated from a critically ill patient and characterized by a multidrug resistant (MDR) profile, including resistance to CZA, M/V, and I/R. Methods: An antimicrobial susceptibility test (AST) was performed by an automated system and E-test and results were interpreted following the EUCAST guidelines. Genomic DNA was extracted using a genomic DNA extraction kit and it was sequenced using the Illumina Nova Seq 6000 platform. Final assembly was manually curated and carefully verified for detection of antimicrobial resistance genes, porins modifications, and virulence factors. Results: The K. pneumoniae isolate belonged to sequence type ST512 and harbored 23 resistance genes, conferring resistance to all antibiotic classes, including blaKPC-31 and blaOXA-181, leading to carbapenems resistance. The truncation of OmpK35 and mutation OmpK36GD were also observed. Conclusions: The genomic characterization demonstrated the high resistant profile of new cr-Kp coharboring class A and D carbapenemases. The presence of KPC-31, as well as the detection of OXA-181 and porin modifications, further limit the therapeutic options, including the novel combinations of β-lactam/β-lactamase inhibitor antibiotics in patients with severe pneumonia caused by cr-Kp.