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

Ceftazidime-avibactam is one of the last resort antimicrobial agents for the treatment of carbapenem-resistant, Gram-negative bacteria. However, metallo-beta-lactamase-producing strains are considered to be ceftazidime-avibactam resistant. Therefore, we evaluated the Becton Dickinson Phoenix 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 test strains displayed ceftazidime-avibactam susceptibility in the Phoenix system and six of these strains were susceptible in Micronaut-S broth microdilution, too. In all nine strains, however, 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 Phoenix system and Micronaut-S broth microdilution were supplemented with zinc. Thereby the detection of phenotypic resistance was improved in the Phoenix system and Micronaut-S broth microdilution.