The emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKp) is a growing concern because of the high mortality rates and limited treatment options. Few reports have examined the in vitro antibacterial activity of novel β-lactam/β-lactamase inhibitor drugs against CR-hvKp. This study investigated the in vitro activity of β-lactam/β-lactamase inhibitor including cefepime/zidebactam, aztreonam/avibactam, imipenem/relabactam and meropenem/vaborbactam toward CR-hvKP isolates. Molecular epidemiological characterization of CR-hvKP strains was performed. A total of 106 non-repetitive clinical CR-hvKP strains were collected from patients at Sichuan Provincial People’s Hospital between August 2018 and December 2023. A VITEK-2 compact system (bioMérieux, France) was used for the preliminary identification of strains and drug susceptibility testing, and matrix-assisted laser desorption/ionization mass spectrometry (Ci-phergen Biosystem, USA) was used to confirm the identity of all strains. CR-hvKP strains were screened using string tests and polymerase chain reaction. The E-test strip method was used to evaluate the in vitro antibacterial activity of novel antimicrobial drugs toward CR-hvKP stains. Molecular characterization of CR-hvKP strains was carried out using polymerase chain reaction amplification of resistance genes, virulence genes, housekeeping genes, and wzi genes. The virulence features of CR-hvKP strains were investigated using the Galleria mellonella infection model. The susceptibility rates of CR-hvKP to cefepime/zidebactam and aztreonam/avibactam all exceeded 90%, with rates of 98.1% and 99.1%, respectively. CR-hvKP exhibited susceptibility rates of 57.5% and 65.1% to imipenem/relebactam and meropenem/vaborbactam, respectively. Sequencing identified ST11–KL64 as the predominant type in CR-hvKP strains. We identified three new ST subtypes, ST8115, ST8116 and ST8117. The most prevalent carbapenemase genes were blaKPC and blaNDM, and approximately 75.5% of CR-hvKP strains carried both blaKPC, blaSHV, and blaCTX-M. Cefepime/zidebactam and aztreonam/avibactam hold great promise for the treatment of CR-hvKP infections. Our findings will not only effectively address the challenge of CR-hvKP resistance, but also provide evidence to support the optimization of clinical therapeutic strategies and further promote the development and application of novel antimicrobial drugs.
Li et al. (Fri,) studied this question.