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Updated: Jan 29, 2026

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors
Published on: December 7, 2014
Ceftazidime/avibactam resistance associated with L169P mutation in the omega loop of KPC-2
Peera Hemarajata1, Romney M Humphries2,3
1Los Angeles Department of Public Health, Downey, CA, USA.
Objectives:
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.
Methods:
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.
Results:
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.
Conclusions:
A novel L169P mutation was identified in KPC-2 and was shown through cloning experiments to confer reduced susceptibility to ceftazidime/avibactam.
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