Molecular and phenotypical characterization of two cases of antibiotic-driven ceftazidime-avibactam resistance in blaKPC-3-harboring Klebsiella pneumoniae

Molecular and phenotypical characterization of two cases of antibiotic-driven ceftazidime-avibactam resistance in blaKPC-3-harboring Klebsiella pneumoniae Carolina Venditti,1 Carla Nisii,1 Silvia D’Arezzo,1 Antonella Vulcano,1 Alessandro Capone,2 Mario Antonini,2 Giuseppe Ippolito,3 Antonino Di Caro11Laboratory of Microbiology, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy; 2Clinical Department, National Institute for Infectious Diseases "L.Spallanzani", Rome, Italy; 3Scientific Direction, National Institute for Infectious Diseases "L.Spallanzani", Rome, ItalyBackground: For years, Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae have represented a serious health problem in hospitals worldwide. Since its approval in 2015, ceftazidime-avibactam (CAZ-AVI) had been successfully used for treating complicated KPC-K. pneumoniae infections, until increasing reports of resistance began to emerge.Methods: Phenotypic tests and molecular analysis were performed in four multidrug-resistant K. pneumoniae isolates, collected from two patients following treatment with CAZ-AVI.Results: In this study, we report two cases of emergence of CAZ-AVI resistance in KPC-3-producing K. pneumoniae isolates, collected from two patients following treatment with CAZ-AVI. Molecular analysis highlighted the D179Y mutation in the blaKPC-3 gene, whose role in the loss of hydrolytic activity (resulting in decreased carpabenem minimum inhibitory concentrations and negative phenotypic tests) of the enzyme has already been shown.Conclusion: Most surveillance schemes aimed at detecting carbapenem-resistant Enterobacteriaceae (CRE) rely on confirmatory phenotypic tests for detecting carbapenemase production. As reports of these treatment-induced, altered CRE phenotypes are increasing, the initial susceptibility testing should be followed by a combination of phenotypic and molecular methods, to make sure that no potential carbapenemase-producing bacteria are missed.Keywords: Klebsiella pneumoniae, carbapenem-resistance, ceftazidime-avibactam