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Background <p>Ceftazidime–avibactam (CAZ–AVI) and imipenem–relebactam (IMI–REL) are both antibiotics with promising prospects for treating <i>Klebsiella pneumoniae</i> carbapenemase (KPC)-producing <i>Klebsiella pneumoniae</i> (KPC-Kp) infections. However, differences in the in vitro activities and resistance mechanisms to CAZ–AVI and IMI–REL in clinical KPC-Kps have not been described.</p> Methods <p>In this study, KPC-Kp isolates from hospitalized patients in China were collected and subjected to antimicrobial susceptibility testing of IMI–REL and CAZ–AVI using the broth microdilution method. Whole-genome sequencing (WGS) and functional validation of mutations were performed on resistant strains, and RT-qPCR was used to determine the expression levels of <i>bla</i><sub>KPC</sub>.</p> Results <p>The results showed that 21 (2.7%) of 782 clinical KPC-Kp strains were CAZ–AVI-resistant, 6 (0.8%) of 782 strains were IMI–REL-resistant, and 5 strains among them were resistant to both CAZ–AVI and IMI–REL. Strains resistant to both CAZ–AVI and IMI–REL can be effectively inhibited by tigecycline and polymyxin B. WGS and complementation experiments showed that KPC mutations are linked to high-level resistance to CAZ–AVI; while OmpK36 mutations may be the vital mechanism of IMI–REL resistance, confers resistance to CAZ–AVI simultaneously. Furthermore, RT-qPCR indicated that elevated <i>bla</i><sub>KPC</sub> expression may play an important role in both CAZ–AVI and IMI–REL resistance.</p> Conclusions <p>In summary, this study suggested that IMI–REL may have superior inhibitory effects in vitro on KPC-Kps than CAZ–AVI, and described the differences in resistance mechanisms between the two antibiotics.</p>

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Comparison of the in vitro activities and resistance mechanisms against imipenem–relebactam and ceftazidime–avibactam in clinical KPC-producing Klebsiella pneumoniae isolated in China

  • 期刊论文

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  • 发表日期：

    2025年2月15日

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  • Yingyi Guo,
  • Likang Yao,
  • Jiong Wang,
  • Yan Zhang,
  • Chuyue Zhuo,
  • Yijing Wang,
  • Xu Yang,
  • Jiahui Li,
  • Nanhao He,
  • Jiakang Chen,
  • Yexin Lin,
  • Shunian Xiao,
  • Zhiwei Lin,
  • Chao Zhuo

摘要

Background

Ceftazidime–avibactam (CAZ–AVI) and imipenem–relebactam (IMI–REL) are both antibiotics with promising prospects for treating Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (KPC-Kp) infections. However, differences in the in vitro activities and resistance mechanisms to CAZ–AVI and IMI–REL in clinical KPC-Kps have not been described.

Methods

In this study, KPC-Kp isolates from hospitalized patients in China were collected and subjected to antimicrobial susceptibility testing of IMI–REL and CAZ–AVI using the broth microdilution method. Whole-genome sequencing (WGS) and functional validation of mutations were performed on resistant strains, and RT-qPCR was used to determine the expression levels of blaKPC.

Results

The results showed that 21 (2.7%) of 782 clinical KPC-Kp strains were CAZ–AVI-resistant, 6 (0.8%) of 782 strains were IMI–REL-resistant, and 5 strains among them were resistant to both CAZ–AVI and IMI–REL. Strains resistant to both CAZ–AVI and IMI–REL can be effectively inhibited by tigecycline and polymyxin B. WGS and complementation experiments showed that KPC mutations are linked to high-level resistance to CAZ–AVI; while OmpK36 mutations may be the vital mechanism of IMI–REL resistance, confers resistance to CAZ–AVI simultaneously. Furthermore, RT-qPCR indicated that elevated blaKPC expression may play an important role in both CAZ–AVI and IMI–REL resistance.

Conclusions

In summary, this study suggested that IMI–REL may have superior inhibitory effects in vitro on KPC-Kps than CAZ–AVI, and described the differences in resistance mechanisms between the two antibiotics.