Genetic diversity and co-prevalence of ESBLs and PMQR genes among plasmid-mediated AmpC β-lactamase-producing Klebsiella pneumoniae isolates causing urinary tract infection

Abstract

Klebsiella pneumoniae is an opportunistic pathogen that frequently causes nosocomial urinary tract infection (UTI). The aim of this study was to investigate the prevalence of extended-spectrum β-lactamases (ESBL), plasmid-mediated quinolone resistance (PMQR) genes, in acquired AmpC (ac-AmpC) β‑lactamase‑producing K. pneumoniae isolates from patients with nosocomial UTI and to characterize the transmissibility of plasmids harbouring multiple resistance genes. From January 2017 to June 2018, we collected 46 ac-AmpC-producing K. pneumoniae isolates causing UTI from a tertiary care hospital in China. Antimicrobial susceptibility assays showed that non-susceptibility of all isolates to third-generation cephalosporin and fluoroquinolone was very high (>80%). Diverse types of ESBLs and PMQR genes, including bla_SHV-12 (n = 23), bla_SHV-27 (n = 1)_, bla_SHV-28 (n = 2)_, bla_SHV-33 (n = 4), bla_CTX-M-3 (n = 24)_, bla_CTX-M-14 (n = 6)_, bla_CTX-M-15 (n = 6)_, bla_CTX-M-22 (n = 1) and bla_OXA-10 (n = 26)_, as well as qnrA (n = 2), qnrB (n = 39) and qnrS (n = 2) genes were identified amongst AmpC-producing K. pneumoniae isolates. The bla_AmpC, qnrB and several ESBLs genes from six strains harbouring multiple AmpC (at least two ampC) were co-transferrable to recipients via conjugation or electroporation, with IncFIA, IncFIB and IncA/C being the dominant replicons. Conserved genetic context associated with the mobilization of bla_ampC genes was detected. Forty-six isolates were categorized into 25 enterobacterial repetitive intergenic consensus (ERIC) types, and the 6 isolates harbouring multiple AmpC genes belonged to ST1 lineage. This work reports that the emergence of plasmids co-harbouring multiple resistance determinants and mediating the local prevalence in K. pneumoniae causing UTI in China.