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European Journal of Clinical Microbiology & Infectious Diseases

03-05-2024 | Aztreonam | Original Article

In vitro and in vivo activity of ceftazidime/avibactam and aztreonam alone or in combination against mcr-9, serine- and metallo-β-lactamases–co-producing carbapenem-resistant Enterobacter cloacae complex

Authors: Wengang Li, Jisheng Zhang, Yanjun Fu, Jianmin Wang, Longjin Liu, Wenzhang Long, Kaixin Yu, Xinhui Li, Chunli Wei, Xushan Liang, Jin Wang, Chunjiang Li, Xiaoli Zhang

Published in: European Journal of Clinical Microbiology & Infectious Diseases

Abstract

Purpose

Enterobacteriaceae carrying mcr-9, in particularly those also co-containing metallo-β-lactamase (MBL) and TEM type β-lactamase, present potential transmission risks and lack adequate clinical response methods, thereby posing a major threat to global public health. The aim of this study was to assess the antimicrobial efficacy of a combined ceftazidime/avibactam (CZA) and aztreonam (ATM) regimen against carbapenem-resistant Enterobacter cloacae complex (CRECC) co-producing mcr-9, MBL and TEM.

Methods

The in vitro antibacterial activity of CZA plus ATM was evaluated using a time-kill curve assay. Furthermore, the in vivo interaction between CZA plus ATM was confirmed using a Galleria mellonella (G. mellonella) infection model.

Results

All eight clinical strains of CRECC, co-carrying mcr-9, MBL and TEM, exhibited high resistance to CZA and ATM. In vitro time-kill curve analysis demonstrated that the combination therapy of CZA + ATM exerted significant bactericidal activity against mcr-9, MBL and TEM-co-producing Enterobacter cloacae complex (ECC) isolates with a 100% synergy rate observed in our study. Furthermore, in vivo survival assay using Galleria mellonella larvae infected with CRECC strains co-harboring mcr-9, MBL and TEM revealed that the CZA + ATM combination significantly improved the survival rate compared to the drug-treatment alone and untreated control groups.

Conclusion

To our knowledge, this study represents the first report on the in vitro and in vivo antibacterial activity of CZA plus ATM against CRECC isolates co-harboring mcr-9, MBL and TEM. Our findings suggest that the combination regimen of CZA + ATM provides a valuable reference for clinicians to address the increasingly complex antibiotic resistance situation observed in clinical microorganisms.

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Title: In vitro and in vivo activity of ceftazidime/avibactam and aztreonam alone or in combination against mcr-9, serine- and metallo-β-lactamases–co-producing carbapenem-resistant Enterobacter cloacae complex
Authors: Wengang Li
Jisheng Zhang
Yanjun Fu
Jianmin Wang
Longjin Liu
Wenzhang Long
Kaixin Yu
Xinhui Li
Chunli Wei
Xushan Liang
Jin Wang
Chunjiang Li
Xiaoli Zhang
Publication date: 03-05-2024
Publisher: Springer Berlin Heidelberg
Keywords: Aztreonam
Ceftazidime
Carbapenem Antibiotic
Tigecycline
Published in: European Journal of Clinical Microbiology & Infectious Diseases
Print ISSN: 0934-9723
Electronic ISSN: 1435-4373
DOI: https://doi.org/10.1007/s10096-024-04841-8

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