Comparison of the in vitro activities and resistance mechanisms against imipenem-relebactam and ceftazidime-avibactam in clinical KPC-producing Klebsiella pneumoniae isolated in China.
{"title":"Comparison of the in vitro activities and resistance mechanisms against imipenem-relebactam and ceftazidime-avibactam in clinical KPC-producing Klebsiella pneumoniae isolated in China.","authors":"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","doi":"10.1007/s15010-025-02474-3","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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 bla<sub>KPC</sub>.</p><p><strong>Results: </strong>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 bla<sub>KPC</sub> expression may play an important role in both CAZ-AVI and IMI-REL resistance.</p><p><strong>Conclusions: </strong>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>","PeriodicalId":13600,"journal":{"name":"Infection","volume":" ","pages":""},"PeriodicalIF":5.4000,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Infection","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s15010-025-02474-3","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍：
Infection is a journal dedicated to serving as a global forum for the presentation and discussion of clinically relevant information on infectious diseases. Its primary goal is to engage readers and contributors from various regions around the world in the exchange of knowledge about the etiology, pathogenesis, diagnosis, and treatment of infectious diseases, both in outpatient and inpatient settings.
The journal covers a wide range of topics, including:
Etiology: The study of the causes of infectious diseases.
Pathogenesis: The process by which an infectious agent causes disease.
Diagnosis: The methods and techniques used to identify infectious diseases.
Treatment: The medical interventions and strategies employed to treat infectious diseases.
Public Health: Issues of local, regional, or international significance related to infectious diseases, including prevention, control, and management strategies.
Hospital Epidemiology: The study of the spread of infectious diseases within healthcare settings and the measures to prevent nosocomial infections.
In addition to these, Infection also includes a specialized "Images" section, which focuses on high-quality visual content, such as images, photographs, and microscopic slides, accompanied by brief abstracts. This section is designed to highlight the clinical and diagnostic value of visual aids in the field of infectious diseases, as many conditions present with characteristic clinical signs that can be diagnosed through inspection, and imaging and microscopy are crucial for accurate diagnosis. The journal's comprehensive approach ensures that it remains a valuable resource for healthcare professionals and researchers in the field of infectious diseases.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
