Peera Hemarajata1, Romney M Humphries2,3. 1. Los Angeles Department of Public Health, Downey, CA, USA. 2. Accelerate Diagnostics, Tucson, AZ, USA. 3. Department of Pathology, University of Arizona, Tucson, AZ, USA.
Abstract
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.
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.
Authors: Krisztina M Papp-Wallace; Andrew R Mack; Magdalena A Taracila; Robert A Bonomo Journal: Infect Dis Clin North Am Date: 2020-09-30 Impact factor: 5.982
Authors: Helio S Sader; Paul R Rhomberg; Sukantha Chandrasekaran; Marisol Trejo; Kelley A Fedler; Linda D Boyken; Daniel J Diekema Journal: J Clin Microbiol Date: 2020-03-25 Impact factor: 5.948