Infection and Drug Resistance (Jul 2019)

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

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

Journal volume & issue
Vol. Volume 12
pp. 1935 – 1940

Abstract

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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

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