Characterization of KPC-82, a KPC-2 Variant Conferring Resistance to Ceftazidime-Avibactam in a Carbapenem-Nonsusceptible Clinical Isolate of Citrobacter koseri

KPC-82 is a KPC-2 variant identified in a carbapenem-nonsusceptible Citrobacter koseri that confers high-level resistance to ceftazidime-avibactam. Genomic analysis revealed that is carried by a chromosomally integrated Tn transposon (disrupting porin gene ) and evolved by a 6-nucleotide tandem repe...

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Bibliographic Details
Published in:Antimicrobial agents and chemotherapy 2021-06, Vol.65 (7), p.e0015021-e0015021
Main Authors: Lebreton, Francois, Corey, Brendan W, McElheny, Christi L, Iovleva, Alina, Preston, Lan, Margulieux, Katie R, Cybulski, Robert J, Mc Gann, Patrick, Doi, Yohei, Bennett, Jason W
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - pharmacology
Azabicyclo Compounds - pharmacology
Bacterial Proteins - genetics
beta-Lactamases - genetics
Carbapenems - pharmacology
Ceftazidime - pharmacology
Citrobacter koseri
Drug Combinations
Klebsiella pneumoniae
Mechanisms of Resistance
Microbial Sensitivity Tests
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Summary:KPC-82 is a KPC-2 variant identified in a carbapenem-nonsusceptible Citrobacter koseri that confers high-level resistance to ceftazidime-avibactam. Genomic analysis revealed that is carried by a chromosomally integrated Tn transposon (disrupting porin gene ) and evolved by a 6-nucleotide tandem repeat duplication causing a two-amino-acid insertion (Ser-Asp) within the Ala -Ser loop. Similar to related KPC variants, KPC-82 showed decreased carbapenemase activity when expressed in a heterologous background and remained susceptible to carbapenem/β-lactamase inhibitor combinations.
ISSN:0066-4804
1098-6596
DOI:10.1128/AAC.00150-21