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 blaKPC and blaNDM, and approximately 75.5% of CR-hvKP carried blaKPC, blaSHV, and blaCTX-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.