Inhibition Activity of Avibactam against Nocardia farcinica ?-Lactamase FARIFM10152.

ABSTRACT: Nocardia farcinica, one of the most frequent pathogenic species responsible for nocardiosis, is characterized by frequent brain involvement and resistance to ?-lactams mediated by a class A ?-lactamase. Kinetic parameters for hydrolysis of various ?-lactams by FARIFM10152 from strain IFM 10152 were determined by spectrophotometry revealing a high catalytic activity (k cat/Km ) for amoxicillin, aztreonam, and nitrocefin. For cephems, k cat/Km 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/Ki ) of (1.7?±?0.3) × 104 M-1 s-1 The 50% effective concentrations (EC50s) of avibactam and clavulanate were 0.060?±?0.007??M and 0.28?±?0.06??M, respectively. Amoxicillin, cefotaxime, imipenem, and meropenem MICs were measured for ten clinical strains in the presence of avibactam and clavulanate. At 4??g/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. At 0.4??g/ml, amoxicillin susceptibility (MIC ? 8??g/ml) was restored for 9 out of 10 strains by avibactam but only for 4 out of 10 strains by clavulanate. Together, these results indicate that avibactam was at least as potent as clavulanate, suggesting that the amoxicillin-avibactam combination could be considered as an option for the rescue treatment of N. farcinica infections if clavulanate cannot be used.

SUBMITTER: Lebeaux D 

PROVIDER: S-EPMC6985717 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature