A Ceftazidime-Avibactam-Resistant and Carbapenem-Susceptible Klebsiella pneumoniae Strain Harboring blaKPC-14 Isolated in New York City

Abstract

Ceftazidime-avibactam is a potent antibiotic combination against Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae Here, we describe a unique ceftazidime-avibactam-resistant and carbapenem-susceptible K. pneumoniae strain harboring a novel bla_KPC-14 variant. This strain was isolated from a New York City patient in 2003, which predates the introduction of avibactam. Despite resistance to ceftazidime-avibactam, the strain was susceptible to imipenem-relebactam and meropenem-vaborbactam. Comprehensive genomic sequencing revealed that bla_KPC-14 is harbored on an ST6 IncN plasmid associated with the early spread of bla_KPCIMPORTANCE KPC is currently the most common carbapenemase identified in the United States. More than 40 KPC variants have been described, of which KPC-2 and KPC-3 are the most frequent clinical variants. However, our understanding of the genetic structures and β-lactam resistance profiles of other novel KPC variants remains incomplete. Here, we report a novel bla_KPC variant (bla_KPC-14) and the complete genome sequence of bla_KPC-14-harboring K. pneumoniae strain BK13048, which is susceptible to carbapenems but resistant to ceftazidime-avibactam. To the best of our knowledge, this is one of the earliest KPC-producing K. pneumoniae strains exhibiting resistance to ceftazidime-avibactam.

Keywords: KPC; antimicrobial resistance; carbapenem; ceftazidime-avibactam; plasmid; selection.

FIG 1

Structures of plasmids p12 (GenBank accession no. FJ223605), pBK13048_KPC14 (accession no. CP045022), and pKm38_N (accession no. KY128483). Colored arrows indicate open reading frames, with blue, orange, green, red, and purple arrows representing replication genes, plasmid backbone genes, mobile elements, plasmid transfer genes, and antimicrobial and heavy metal resistance genes, respectively. Blue shading indicates regions of shared homology among different elements.