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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
Li, Wengang; Zhang, Jisheng; Fu, Yanjun; Wang, Jianmin; Liu, Longjin; Long, Wenzhang; Yu, Kaixin; Li, Xinhui; Wei, Chunli; Liang, Xushan; Wang, Jin; Li, Chunjiang; Zhang, Xiaoli
- 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.
- Subjects
ENTEROBACTER cloacae; AZTREONAM; GREATER wax moth; CEFTAZIDIME; ANTIBACTERIAL agents
- Publication
European Journal of Clinical Microbiology & Infectious Diseases, 2024, Vol 43, Issue 7, p1309
- ISSN
0934-9723
- Publication type
Article
- DOI
10.1007/s10096-024-04841-8