The Effectiveness of Imipenem-Relebactam against Ceftazidime-Avibactam Resistant Variants of the KPC-2 β-Lactamase.

ABSTRACT:

Background

Ceftazidime-avibactam was approved by the FDA to treat infections caused by Enterobacterales carrying bla_KPC-2. However, variants of KPC-2 with amino acid substitutions at position 179 have emerged and confer resistance to ceftazidime-avibactam.

Methods

The activity of imipenem-relebactam was assessed against a panel of 19 KPC-2 D179 variants. KPC-2 and the D179N and D179Y variants were purified for biochemical analyses. Molecular models were constructed with imipenem to assess differences in kinetic profiles.

Results

All strains were susceptible to imipenem-relebactam, but resistant to ceftazidime (19/19) and ceftazidime-avibactam (18/19). KPC-2 and the D179N variant hydrolyzed imipenem, but the D179N variant's rate was much slower. The D

SUBMITTER: Papp-Wallace KM 

PROVIDER: S-EPMC10215400 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature