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Klebsiella pneumoniae carbapenemase (KPC) producer resistant to ceftazidime-avibactam due to a deletion in the blaKPC3 gene.
Clin Microbiol Infect. 2020 Jul; 26(7):946.e1-946.e3.CM

Abstract

OBJECTIVES

Carbapenemase-producing strains of Klebsiella pneumoniae (KPC) are a great health concern, and therapy with ceftazidime-avibactam represents a choice for the treatment of infections involving these strains. We report a strain resistant to ceftazidime-avibactam due to a deletion of six nucleotides in the blaKPC gene sequence.

METHODS

Two strains, namely AMP920 and AMP2009, were isolated from the same patient a month apart. Antimicrobial susceptibility testing was performed both by broth microdilution and by Etest. Immunoenzymatic assay to detect carbapenemase was performed for both strains. The blaKPC gene of both strains was amplified by PCR and sequenced. Enzyme activity towards carbapenems was tested by the CarbaNP test and hydrolysis spectrophotometer assay.

RESULTS

The two isolates differed in antimicrobial susceptibility. AMP920 showed meropenem and imipenem resistance (MIC 32 and 32 mg/mL). A month later the carbapenem MIC decreased to 8 and 1 mg/mL respectively, while the ceftazidime-avibactam MIC increased from 1 to 16 mg/mL. Both isolates showed a positive immunoenzymatic test for the KPC enzyme, but only AMP920 showed a positive CarbaNP test hydrolysing imipenem. The BlaKPC gene was amplified in both strains. After sequencing, the two amplicons showed a KPC3 variant. The gene of the second isolate showed a deletion of six nucleotides at 498-503, resulting in a mutant variant with the deletion of glutamic acid and leucine residues at positions 167 and 168.

CONCLUSIONS

We detected a new deletion in the blaKPC gene of a clinical strain of K. pneumoniae which resulted in resistance to ceftazidime-avibactam. The amino acids deleted are in the Ω loop (amino acids 165-179) of the KPC enzyme, enhancing ceftazidime affinity and preventing avibactam binding.

Authors+Show Affiliations

Department of Diagnostics and Public Health, University of Verona, Verona, Italy.Department of Diagnostics and Public Health, University of Verona, Verona, Italy.Department of Diagnostics and Public Health, University of Verona, Verona, Italy.Department of Diagnostics and Public Health, University of Verona, Verona, Italy. Electronic address: annarita.mazzariol@univr.it.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32061796

Citation

Antinori, E, et al. "Klebsiella Pneumoniae Carbapenemase (KPC) Producer Resistant to Ceftazidime-avibactam Due to a Deletion in the blaKPC3 Gene." Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases, vol. 26, no. 7, 2020, pp. 946.e1-946.e3.
Antinori E, Unali I, Bertoncelli A, et al. Klebsiella pneumoniae carbapenemase (KPC) producer resistant to ceftazidime-avibactam due to a deletion in the blaKPC3 gene. Clin Microbiol Infect. 2020;26(7):946.e1-946.e3.
Antinori, E., Unali, I., Bertoncelli, A., & Mazzariol, A. (2020). Klebsiella pneumoniae carbapenemase (KPC) producer resistant to ceftazidime-avibactam due to a deletion in the blaKPC3 gene. Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases, 26(7), e1-e3. https://doi.org/10.1016/j.cmi.2020.02.007
Antinori E, et al. Klebsiella Pneumoniae Carbapenemase (KPC) Producer Resistant to Ceftazidime-avibactam Due to a Deletion in the blaKPC3 Gene. Clin Microbiol Infect. 2020;26(7):946.e1-946.e3. PubMed PMID: 32061796.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Klebsiella pneumoniae carbapenemase (KPC) producer resistant to ceftazidime-avibactam due to a deletion in the blaKPC3 gene. AU - Antinori,E, AU - Unali,I, AU - Bertoncelli,A, AU - Mazzariol,A, Y1 - 2020/02/12/ PY - 2019/11/03/received PY - 2020/02/02/revised PY - 2020/02/06/accepted PY - 2020/2/18/pubmed PY - 2021/1/29/medline PY - 2020/2/17/entrez KW - Ceftazidime–avibactam resistance KW - KPC carbapenemase KW - KPC deletion KW - KPC mutations KW - KPC producing K. pneumoniae SP - 946.e1 EP - 946.e3 JF - Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases JO - Clin Microbiol Infect VL - 26 IS - 7 N2 - OBJECTIVES: Carbapenemase-producing strains of Klebsiella pneumoniae (KPC) are a great health concern, and therapy with ceftazidime-avibactam represents a choice for the treatment of infections involving these strains. We report a strain resistant to ceftazidime-avibactam due to a deletion of six nucleotides in the blaKPC gene sequence. METHODS: Two strains, namely AMP920 and AMP2009, were isolated from the same patient a month apart. Antimicrobial susceptibility testing was performed both by broth microdilution and by Etest. Immunoenzymatic assay to detect carbapenemase was performed for both strains. The blaKPC gene of both strains was amplified by PCR and sequenced. Enzyme activity towards carbapenems was tested by the CarbaNP test and hydrolysis spectrophotometer assay. RESULTS: The two isolates differed in antimicrobial susceptibility. AMP920 showed meropenem and imipenem resistance (MIC 32 and 32 mg/mL). A month later the carbapenem MIC decreased to 8 and 1 mg/mL respectively, while the ceftazidime-avibactam MIC increased from 1 to 16 mg/mL. Both isolates showed a positive immunoenzymatic test for the KPC enzyme, but only AMP920 showed a positive CarbaNP test hydrolysing imipenem. The BlaKPC gene was amplified in both strains. After sequencing, the two amplicons showed a KPC3 variant. The gene of the second isolate showed a deletion of six nucleotides at 498-503, resulting in a mutant variant with the deletion of glutamic acid and leucine residues at positions 167 and 168. CONCLUSIONS: We detected a new deletion in the blaKPC gene of a clinical strain of K. pneumoniae which resulted in resistance to ceftazidime-avibactam. The amino acids deleted are in the Ω loop (amino acids 165-179) of the KPC enzyme, enhancing ceftazidime affinity and preventing avibactam binding. SN - 1469-0691 UR - https://www.unboundmedicine.com/medline/citation/32061796/Klebsiella_pneumoniae_carbapenemase__KPC__producer_resistant_to_ceftazidime_avibactam_due_to_a_deletion_in_the_blaKPC3_gene_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1198-743X(20)30086-0 DB - PRIME DP - Unbound Medicine ER -