Detection of KPC-216, a Novel KPC-3 Variant, in a Clinical Isolate of <i>Klebsiella pneumoniae</i> ST101 Co-Resistant to Ceftazidime-Avibactam and Cefiderocol

Abstract

Background: Carbapenemase-producing Klebsiella pneumoniae (CP-KP) represents a global threat to public health, with limited antimicrobial therapeutic options. In this study, we analyzed a ceftazidime/avibactam (CAZ-AVI)-resistant K. pneumoniae isolate obtained from a patient previously exposed to CAZ-AVI expressing a novel K. pneumoniae carbapenemase (KPC)-3 variant. Methods: Antimicrobial susceptibility testing was performed using reference broth microdilution. Whole-genome sequencing (WGS) was performed using Illumina and Nanopore Technologies. Short- and long-reads were combined with Unicycler. Assemblies were investigated for multilocus sequence typing (MLST), antimicrobial resistance genes, porins, and plasmids. Results: The K. pneumoniae isolate (KP_RM_1) was resistant to CAZ-AVI, expanded-spectrum cephalosporins, amikacin, ertapenem, and cefiderocol (FDC) but was susceptible to tigecycline, colistin, trimethoprim/sulfamethoxazole, meropenem–vaborbactam, and imipenem–relebactam. WGS revealed that the KP_RM_1 genome is composed of a single chromosome of 5 Mbp and five circular plasmids. Further analysis showed the presence of novel blaKPC-216 located on a 72 kb plasmid. KPC-216 differs from KPC-3 by a Lysin (K) insertion at position 168 (+K168). Conclusions: We report the identification of a new KPC-3 variant associated with CAZ-AVI resistance. The KPC variants associated with CAZ-AVI resistance should be determined to promptly inform clinicians and start the appropriate antimicrobial therapy.

Keywords

• ceftazidime-avibactam
• cefiderocol
• cross-resistance
• KPC-216
• ESKAPE