Inhibition activity of Nocardia farcinica β-lactamase FAR IFM10152 by avibactam.

Inhibition activity of Nocardia farcinica β-lactamase FAR IFM10152 by avibactam. Antimicrob Agents Chemother. 2019 Nov 11;: Authors: Lebeaux D, Ourghanlian C, Dorchène D, Soroka D, Edoo Z, Compain F, Arthur M Abstract Nocardia farcinica, one of the most frequent pathogenic species responsible for nocardiosis is characterized by frequent brain involvement and resistance to β-lactams mediated by a class A β-lactamase. Kinetic parameters for hydrolysis of various β-lactams by FARIFM10152 from strain IFM10152 were determined by spectrophotometry revealing a high catalytic activity (k cat/K m) for amoxicillin, aztreonam, and nitrocefin. For cephems, k cat/K m was lower but remained greater than 104 M-1 s-1 A low catalytic activity was observed for meropenem, imipenem, and ceftazidime hydrolysis. FARIFM10152 inhibition by avibactam and clavulanate was compared using nitrocefin as a reporter substrate. FARIFM10152 was efficaciously inhibited by avibactam with a carbamoylation rate constant (k 2/K i) of (1.7 ± 0.3) x 104 M-1 s-1 EC50s of avibactam and clavulanate were 0.060 ± 0.007 μM and 0.28 ± 0.06 μM, respectively. Amoxicillin, cefotaxime, imipenem, and meropenem MICs were measured for ten clinical strains in the presence of avibactam and clavulanate. At 4 μg/mL, avibactam and clavulanate restored amoxicillin susceptibility in all but one of the tested strains but had no effect on the MICs of cefotaxime, imipenem, and meropenem...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research