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

锌水平升高有利于产生金属-β-内酰胺酶的革兰氏阴性菌对头孢他啶-阿维巴坦的耐药性的表型检测

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作者:Michaela Simon, Roman G Gerlach, Yvonne Pfeifer, Niels Pfennigwerth, Sören G Gatermann, Agnes Schröder, Andreas Hiergeist, Axel Hamprecht, Tamara Rügamer, André Gessner, Jonathan Jantsch

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.

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