Increased zinc levels facilitate phenotypic detection of ceftazidime-avibactam resistance in metallo-beta-lactamase-producing Gram-negative bacteria

Simon, Michaela and Gerlach, Roman G. and Pfeifer, Yvonne and Pfennigwerth, Niels and Gatermann, Soren G. and Schroeder, Agnes and Hiergeist, Andreas and Hamprecht, Axel and Ruegamer, Tamara and Gessner, Andre and Jantsch, Jonathan (2022) Increased zinc levels facilitate phenotypic detection of ceftazidime-avibactam resistance in metallo-beta-lactamase-producing Gram-negative bacteria. FRONTIERS IN MICROBIOLOGY, 13: 977330. ISSN , 1664-302X

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Abstract

Ceftazidime-avibactam is one of the last resort antimicrobial agents for the treatment of carbapenem-resistant, Gram-negative bacteria. Metallo-beta-lactamase-producing bacteria are considered to be ceftazidime-avibactam resistant. Here, we evaluated a semi-automated antimicrobial susceptibility testing system regarding its capability to detect phenotypic ceftazidime-avibactam resistance in 176 carbapenem-resistant, metallo-beta-lactamase-producing Enterobacterales and Pseudomonas aeruginosa isolates. Nine clinical isolates displayed ceftazidime-avibactam susceptibility in the semi-automated system and six of these isolates were susceptible by broth microdilution, too. In all nine isolates, metallo-beta-lactamase-mediated hydrolytic activity was demonstrated with the EDTA-modified carbapenemase inactivation method. As zinc is known to be an important co-factor for metallo-beta-lactamase activity, test media of the semi-automated antimicrobial susceptibility testing system and broth microdilution were supplemented with zinc. Thereby, the detection of phenotypic resistance was improved in the semi-automated system and in broth microdilution. Currently, ceftazidime-avibactam is not approved as treatment option for infections by metallo-beta-lactamase-producing, Gram-negative bacteria. In infections caused by carbapenem-resistant Gram-negatives, we therefore recommend to rule out the presence of metallo-beta-lactamases with additional methods before initiating ceftazidime-avibactam treatment.

Item Type: Article
Uncontrolled Keywords: ENTEROBACTERIACEAE; CARBAPENEMASES; Enterobacterales; Pseudomonas aeruginosa; metallo-beta-lactamases; ceftazidime-avibactam; zinc; antimicrobial susceptibility testing; Phoenix; Micronaut
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene
Depositing User: Dr. Gernot Deinzer
Date Deposited: 22 Feb 2024 14:10
Last Modified: 22 Feb 2024 14:10
URI: https://pred.uni-regensburg.de/id/eprint/57752

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