Emergence of Ceftazidime- and Avibactam-Resistant Klebsiella pneumoniae Carbapenemase-Producing Pseudomonas aeruginosa in China

ABSTRACT

Klebsiella pneumoniae carbapenemase (KPC)-producing Pseudomonas aeruginosa (KPC-PA) has been reported sporadically. However, epidemiological and antimicrobial susceptibility data specific for KPC-PA are lacking. We collected 374 carbapenem-resistant P. aeruginosa (CRPA) isolates from seven hospitals in China from June 2016 to February 2019 and identified the bla _KPC-2 gene in 40.4% ( n = 151/374) of the isolates. Approximately one-half of all KPC-PA isolates ( n = 76/151; 50.3%) were resistant to ceftazidime-avibactam (CAZ-AVI). Combining Kraken2 taxonomy identification and Nanopore sequencing, we identified eight plasmid types, five of which carried bla _KPC-2, and 13 combination patterns of these plasmid types. In addition, we identified IS 26-ΔTn 6296 and Tn 1403-like–ΔTn 6296 as the two mobile genetic elements that mediated bla _KPC-2 transmission. bla _KPC-2 plasmid curing in 28 strains restored CAZ-AVI susceptibility, suggesting that bla _KPC-2 was the mediator of CAZ-AVI resistance. Furthermore, the bla _KPC-2 copy number was found to correlate with KPC expression and, therefore, CAZ-AVI resistance. Taken together, our results suggest that KPC-PA is becoming a clinical threat and that using CAZ-AVI to treat this specific pathogen should be done with caution.

IMPORTANCE Previous research has reported several cases of KPC-PA strains and three KPC-encoding P. aeruginosa plasmid types in China. However, the prevalence and clinical significance of KPC-PA are not available. In addition, the susceptibility of the strains to CAZ-AVI remains unknown. Samples in this study were collected from seven tertiary hospitals prior to CAZ-AVI clinical approval in China. Therefore, our results represent a retrospective study establishing the baseline efficacy of the novel β-lactam/β-lactamase combination agent for treating KPC-PA infections. The observed correlation between the bla _KPC copy number and CAZ-AVI resistance suggests that close monitoring of the susceptibility of the strain during treatment is required. It would also be beneficial to screen for the bla _KPC gene in CRPA strains for antimicrobial surveillance purposes.