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

Language
en
Document Type
Article
Issue Date
2022-12-06
First published
2022-11-22
Issue Year
2022
Authors
Simon, Michaela
Gerlach, Roman G.
Pfeifer, Yvonne
Pfennigwerth, Niels
Gatermann, Sören G.
Schröder, Agnes
Hiergeist, Andreas
Hamprecht, Axel
Rügamer, Tamara
Gessner, André
Editor
Publisher
Frontiers Media S.A.
Abstract

Ceftazidime-avibactam is one of the last resort antimicrobial agents for the treatment of carbapenem-resistant, Gram-negative bacteria. Metallo-β-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-β-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-β-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-β-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-β-lactamase-producing, Gram-negative bacteria. In infections caused by carbapenem-resistant Gram-negatives, we therefore recommend to rule out the presence of metallo-β-lactamases with additional methods before initiating ceftazidime-avibactam treatment.

Journal Title
Frontiers in Microbiology
Volume
13
Citation
Frontiers in Microbiology 13 (2022): 977330. <https://www.frontiersin.org/articles/10.3389/fmicb.2022.977330/full>
Zugehörige ORCIDs