Synergy between Aztreonam and Ceftazidime-Avibactam against Gram-negative isolates producing Metallo Beta-Lactamase and occurrence of blaCMY-42 gene among these isolates.

Elgabeery, Rana Ehab; Abdalraheem, Taysser Mahmoud; Abd El-Wahab, Marwa Ahmed; Alm El-Din, Rasha Abd-Elhamid; Shahin, Asmaa Mohamed

doi:10.21608/mid.2025.383328.2772

	Synergy between Aztreonam and Ceftazidime-Avibactam against Gram-negative isolates producing Metallo Beta-Lactamase and occurrence of blaCMY-42 gene among these isolates.
Microbes and Infectious Diseases
Articles in Press, Accepted Manuscript, Available Online from 28 May 2025
Document Type: Original Article
DOI: 10.21608/mid.2025.383328.2772
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Authors
Rana Ehab Elgabeery ¹; Taysser Mahmoud Abdalraheem ²; Marwa Ahmed Abd El-Wahab ¹; Rasha Abd-Elhamid Alm El-Din ¹; Asmaa Mohamed Shahin¹
¹Department of Medical Microbiology and Immunology, Faculty of Medicine, Tanta University, Egypt
²Department of Anaesthesiology, Surgical Intensive Care and Pain Medicine, Faculty of Medicine, Tanta University, Egypt
Abstract
Background: Metallo beta-lactamase-producing Gram-negative bacteria often co-harbor multiple resistance mechanisms, necessitating combination therapies for effective treatment. Aztreonam plus ceftazidime-avibactam has emerged as a potential therapy. Objectives: This work aimed to identify Metallo beta-lactamase, aztreonam-resistant Gram-negative isolates in patients admitted to ICUs of Tanta University Hospitals, evaluate phenotypic methods for detecting synergy of this combination, and explore the presence of the bla_CMY-42gene among these isolates. Methods: Specimens were collected from ICUs, Metallo beta-lactamase-producing Gram-negative isolates were identified using the mCIM/eCIM test, and their antibiotic susceptibility was assessed through disc diffusion. The synergy between aztreonam and ceftazidime-avibactam was tested by reference broth microdilution, other methods for detecting synergy were evaluated, and the bla_CMY-42genewas detected using conventional PCR. Results: Among 60 aztreonam-resistant metallo beta-lactamase-producing isolates, 29 were Klebsiella spp., 15 were E. coli, and 16 were Pseudomonas spp. Most isolates exhibited extensive drug resistance profiles. Aztreonam and ceftazidime-avibactam synergy was observed in 78.3% of isolates. Klebsiella spp. showed the highest synergy rates. The disc elution showed the best agreement with the reference method (96.7%), followed by the supplemented agar disc diffusion (95%). The bla_CMY-42gene was detected in 31.7% of isolates, with a significant correlation to resistance against the combination as it was detected in 92.3% of non-synergistic isolates. Conclusion: Aztreonam+Ceftazidime-avibactam offers a therapeutic option against metallo beta-lactamase. The presence of bla_CMY-42significantly reduces synergy. The disc elution was a reliable phenotypic test for detecting this synergy.
Keywords
Keywords: Metallo beta-lactamase; Synergy; Aztreonam; Ceftazidime-avibactam; blaCMY-42


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