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

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 gene in 40.4% ( = 151/374) of the isolates. Approximately one-half of all KPC-PA isolates ( = 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 , and 13 combination patterns of these plasmid types. In addition, we identified IS-ΔTn and Tn-like-ΔTn as the two mobile genetic elements that mediated transmission. plasmid curing in 28 strains restored CAZ-AVI susceptibility, suggesting that was the mediator of CAZ-AVI resistance. Furthermore, the 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. 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 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 gene in CRPA strains for antimicrobial surveillance purposes.