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

Authors Venditti C, Nisii C, D’Arezzo S, Vulcano A, Capone A, Antonini M, Ippolito G, Di Caro A

Received 8 March 2019

Accepted for publication 13 April 2019

Published 3 July 2019 Volume 2019:12 Pages 1935—1940


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 3

Editor who approved publication: Dr Sahil Khanna

Carolina Venditti,1 Carla Nisii,1 Silvia D’Arezzo,1 Antonella Vulcano,1 Alessandro Capone,2 Mario Antonini,2 Giuseppe Ippolito,3 Antonino Di Caro1

1Laboratory 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, Italy

Background: 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

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