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Molecular and phenotypical characterization of two cases of antibiotic-driven ceftazidime-avibactam resistance in bla KPC-3-harboring Klebsiella pneumoniae.
Infect Drug Resist 2019; 12:1935-1940ID

Abstract

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 bla KPC-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.

Authors+Show Affiliations

Laboratory of Microbiology, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy.Laboratory of Microbiology, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy.Laboratory of Microbiology, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy.Laboratory of Microbiology, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy.Clinical Department, National Institute for Infectious Diseases "L.Spallanzani", Rome, Italy.Clinical Department, National Institute for Infectious Diseases "L.Spallanzani", Rome, Italy.Scientific Direction, National Institute for Infectious Diseases "L.Spallanzani", Rome, Italy.Laboratory of Microbiology, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31308713

Citation

Venditti, Carolina, et al. "Molecular and Phenotypical Characterization of Two Cases of Antibiotic-driven Ceftazidime-avibactam Resistance in Bla KPC-3-harboring Klebsiella Pneumoniae." Infection and Drug Resistance, vol. 12, 2019, pp. 1935-1940.
Venditti C, Nisii C, D'Arezzo S, et al. Molecular and phenotypical characterization of two cases of antibiotic-driven ceftazidime-avibactam resistance in bla KPC-3-harboring Klebsiella pneumoniae. Infect Drug Resist. 2019;12:1935-1940.
Venditti, C., Nisii, C., D'Arezzo, S., Vulcano, A., Capone, A., Antonini, M., ... Di Caro, A. (2019). Molecular and phenotypical characterization of two cases of antibiotic-driven ceftazidime-avibactam resistance in bla KPC-3-harboring Klebsiella pneumoniae. Infection and Drug Resistance, 12, pp. 1935-1940. doi:10.2147/IDR.S207993.
Venditti C, et al. Molecular and Phenotypical Characterization of Two Cases of Antibiotic-driven Ceftazidime-avibactam Resistance in Bla KPC-3-harboring Klebsiella Pneumoniae. Infect Drug Resist. 2019;12:1935-1940. PubMed PMID: 31308713.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular and phenotypical characterization of two cases of antibiotic-driven ceftazidime-avibactam resistance in bla KPC-3-harboring Klebsiella pneumoniae. AU - Venditti,Carolina, AU - Nisii,Carla, AU - D'Arezzo,Silvia, AU - Vulcano,Antonella, AU - Capone,Alessandro, AU - Antonini,Mario, AU - Ippolito,Giuseppe, AU - Di Caro,Antonino, Y1 - 2019/07/03/ PY - 2019/03/08/received PY - 2019/04/13/accepted PY - 2019/7/17/entrez PY - 2019/7/17/pubmed PY - 2019/7/17/medline KW - Klebsiella pneumoniae KW - carbapenem-resistance KW - ceftazidime-avibactam SP - 1935 EP - 1940 JF - Infection and drug resistance JO - Infect Drug Resist VL - 12 N2 - 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 bla KPC-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. SN - 1178-6973 UR - https://www.unboundmedicine.com/medline/citation/31308713/Molecular_and_phenotypical_characterization_of_two_cases_of_antibiotic_driven_ceftazidime_avibactam_resistance_in_bla_KPC_3_harboring_Klebsiella_pneumoniae_ L2 - https://dx.doi.org/10.2147/IDR.S207993 DB - PRIME DP - Unbound Medicine ER -