In vitro antimicrobial activity of six novel β-lactam and β-lactamase inhibitor combinations and cefiderocol against NDM-producing Enterobacterales in China

Xinmeng Liu; Ziyao Li; Feilong Zhang; Xinrui Yang; Zichen Lei; Chen Li; Yongli Wu; Jiankang Zhao; Yulin Zhang; Yanning Hu; FangFang Shen; Pingbang Wang; Junwen Yang; Yulei Liu; Huihui Shi; Binghuai Lu

doi:10.1016/j.ijantimicag.2024.107407

In vitro antimicrobial activity of six novel β-lactam and β-lactamase inhibitor combinations and cefiderocol against NDM-producing Enterobacterales in China

Int J Antimicrob Agents. 2024 Dec 11;65(2):107407. doi: 10.1016/j.ijantimicag.2024.107407. Online ahead of print.

Authors

Xinmeng Liu¹, Ziyao Li², Feilong Zhang¹, Xinrui Yang³, Zichen Lei⁴, Chen Li⁵, Yongli Wu³, Jiankang Zhao⁶, Yulin Zhang⁶, Yanning Hu¹, FangFang Shen⁷, Pingbang Wang⁸, Junwen Yang⁹, Yulei Liu¹⁰, Huihui Shi¹¹, Binghuai Lu¹²

Affiliations

¹ Peking University China-Japan Friendship School of Clinical Medicine, China-Japan Friendship Hospital, Beijing, China; Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, National Center for Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China.
² Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, National Center for Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China; China-Japan Friendship Institute of Clinical Medical Sciences, Beijing, China; Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China; Changping Laboratory, Beijing, China.
³ Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, National Center for Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China; Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
⁴ Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, National Center for Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China; China-Japan Friendship Institute of Clinical Medical Sciences, Beijing, China; Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
⁵ Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, National Center for Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China; Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China; Liuyang Traditional Chinese Medicine Hospital, Changsha, Hunan, China.
⁶ Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, National Center for Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China.
⁷ Heping Hospital affiliated with Changzhi Medical College, Changzhi, Shanxi, China.
⁸ The People's Hospital of Liuyang, Changsha, Hunan, China.
⁹ Department of Laboratory Medicine, Zhengzhou Key Laboratory of Children's Infection and Immunity, Children's Hospital Affiliated with Zhengzhou University, Zhengzhou, Henan, China.
¹⁰ Department of Laboratory Medicine, Beijing Anzhen Hospital, Beijing, China.
¹¹ Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong) Nantong, Jiangsu, China.
¹² Peking University China-Japan Friendship School of Clinical Medicine, China-Japan Friendship Hospital, Beijing, China; Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, National Center for Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China; China-Japan Friendship Institute of Clinical Medical Sciences, Beijing, China; Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China. Electronic address: [email protected].

PMID: 39672348
DOI: 10.1016/j.ijantimicag.2024.107407

Abstract

Introduction: To date, the global prevalence of New Delhi metallo-β-lactamase (NDM) in carbapenem-resistant Enterobacterales (CRE) has been of concern, which is not inhibited by classical β-lactamase inhibitors (BLIs). In this study, we investigated the newly developed antimicrobial agents or inhibitors against NDM-producing Enterobacterales (NPEs).

Methods: The in vitro activities of cefiderocol, cefepime/taniborbactam, meropenem/taniborbactam, cefepime/zidebactam, meropenem/nacubactam, aztreonam/nacubactam and aztreonam/avibactam were analyzed in 204 NPE strains collected in China. The potential resistance mechanisms were identified by whole genome sequencing.

Results: Of 204 NPE strains, 18.1% (37/204) were resistant to cefiderocol, in which cirA deleterious alteration, PBP3 insertion and NDM production were taken as potential resistance mechanisms; 28.9% (59/204) were resistant to cefepime/zidebactam, involving K. pneumoniae with ompK35 deleterious alteration; 22.5% (46/204) were resistant to cefepime/taniborbactam, in which YRIN or YRIK inserted in PBP3 and altered ompC are more frequently detected in the resistant E. coli isolates; 27.9% (57/204) were resistant to meropenem/taniborbactam. Aztreonam/avibactam and aztreonam/nacubactam exhibited excellent activity against NPE. However, meropenem/nacubactam had the lowest activity, with only 49.0% (100/204) of all isolates having MICs of <4/4 mg/L.

Conclusions: Aztreonam/avibactam and aztreonam/nacubactam showed the highest activity against NPE. The potential resistance mechanisms of novel antimicrobial agents against NPE should be under active surveillance.

Keywords: Aztreonam/avibactam; Cefepime/taniborbactam; Cefepime/zidebactam; Cefiderocol; Meropenem/nacubactam; NDM-producing Enterobacterales.