Scholarlink

Background <p>The emergence of carbapenem-resistant hypervirulent <i>Klebsiella pneumoniae</i> (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.</p> Aims <p>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.</p> Methods <p>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 <i>Galleria mellonella</i> infection model.</p> Results <p>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 <i>bla</i><sub>KPC</sub> and <i>bla</i><sub>NDM</sub>, and approximately 75.5% of CR-hvKP strains carried both <i>bla</i><sub>KPC</sub>, <i>bla</i><sub>SHV</sub>, and <i>bla</i><sub>CTX-M</sub>.</p> Conclusions <p>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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Targeting carbapenem-resistant and hypervirulent Klebsiella pneumoniae: in vitro evaluation of cefepime/zidebactam, aztreonam/avibactam, imipenem/relebactam, and meropenem/vaborbactam

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月13日

查看全文
  • Yi Li,
  • Yulian Li,
  • Xun Jia,
  • Huinan Mao,
  • Dan Li,
  • Jie Zhang

摘要

Background

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.

Aims

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.

Methods

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.

Results

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.

Conclusions

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.