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- Title
Ceftazidime/avibactam resistance associated with L169P mutation in the omega loop of KPC-2.
- Authors
Hemarajata, Peera; Humphries, Romney M
- Abstract
<bold>Objectives: </bold>Ceftazidime/avibactam resistance due to mutation in the omega loop of KPC-2 has been documented in vitro and in vivo. This study evaluated the mechanism of ceftazidime/avibactam resistance in a KPC-2-expressing Klebsiella pneumoniae isolated from a patient following ceftazidime/avibactam combination therapy with gentamicin for the treatment of ventilator-associated pneumonia.<bold>Methods: </bold>Ceftazidime/avibactam-susceptible and -resistant isolates of K. pneumoniae were evaluated by broth microdilution and WGS. The KPC-2 gene was cloned from the ceftazidime/avibactam-resistant isolate and evaluated for susceptibility to ceftazidime/avibactam, in an Escherichia coli background.<bold>Results: </bold>A single L169P mutation was identified in the KPC-2 gene between the ceftazidime/avibactam-resistant and -susceptible isolates. The novel KPC-2 allele, designated KPC-35, was shown to confer reduced susceptibility to ceftazidime/avibactam and increased susceptibility to carbapenems, as compared with KPC-2.<bold>Conclusions: </bold>A novel L169P mutation was identified in KPC-2 and was shown through cloning experiments to confer reduced susceptibility to ceftazidime/avibactam.
- Subjects
CEFTAZIDIME; KLEBSIELLA pneumoniae; CARBAPENEMS; CLONING; GENETIC mutation; AMINO acids; ANTIBIOTICS; COMPARATIVE studies; ENZYME inhibitors; HYDROLASES; KLEBSIELLA; RESEARCH methodology; MEDICAL cooperation; MICROBIAL sensitivity tests; ORGANIC compounds; RESEARCH; EVALUATION research; PHARMACODYNAMICS
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 2019, Vol 74, Issue 5, p1241
- ISSN
0305-7453
- Publication type
journal article
- DOI
10.1093/jac/dkz026