Susceptibility Studies of Novel Antimicrobial Drugs Against Carbapenem‐Resistant and Hypervirulent Klebsiella pneumoniae

ABSTRACT Background Carbapenem‐resistant hypervirulent Klebsiella pneumoniae (CR‐hvKp) is a growing concern due to high mortality and limited therapies, with scarce data on novel antimicrobials in vitro activity against it. Aims This research evaluated the in vitro efficacy of six novel antimicrobial drugs including ceftolozane/tazobactam, cefiderocol, eravacycline, omadacycline, temocillin, and plazomicin, against CR‐hvKP and characterize its molecular epidemiology. Methods 106 non‐repetitive clinical CR‐hvKP strains were collected from Sichuan Provincial People's Hospital between August 2018 and December 2023. CR‐hvKP were identified using VITEK‐2 Compact and MALDI‐TOF MS, confirmed via string tests and PCR. The E‐test strip method assessed the in vitro antibacterial activity of novel antimicrobial drugs against CR‐hvKP. The molecular characterization of CR‐hvKP was conducted by PCR to amplify resistance genes, virulence genes, housekeeping genes, and wzi genes. The Galleria mellonella infection model explored the virulence characteristics of CR‐hvKP strains. Results CR‐hvKP had a relatively high susceptibility rate of 96.2% to cefiderocol, showing good antibacterial activity, whereas ceftolozane/tazobactam, temocillin, omadacycline, eravacycline, and plazomicin exhibited high resistance rates (81.1%–99.1%). ST11‐KL64 was the predominant type in CR‐hvKP strains. We identified three new ST subtypes, ST8115, ST8116 and ST8117. The most prevalent carbapenemase genes were bla KPC and bla NDM , and approximately 75.5% of CR‐hvKP carried bla KPC , bla SHV , and bl a CTX‐M . Conclusions Cefiderocol appears highly promising as a therapy for 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.