Potent inhibitory activity of taniborbactam towards NDM-1 and NDM-1
Anti-Bacterial Agents
/ pharmacology
Borinic Acids
/ pharmacology
Carboxylic Acids
/ pharmacology
Cefepime
/ pharmacology
Drug Contamination
Drug Resistance, Bacterial
/ drug effects
Drug Synergism
Enterobacteriaceae
/ drug effects
Microbial Sensitivity Tests
beta-Lactamase Inhibitors
/ pharmacology
beta-Lactamases
Antibiotic resistance
Inhibitors
Metallo-β-lactamases
NDM-1
Taniborbactam
VNRX-5133
Journal
International journal of antimicrobial agents
ISSN: 1872-7913
Titre abrégé: Int J Antimicrob Agents
Pays: Netherlands
ID NLM: 9111860
Informations de publication
Date de publication:
Jan 2021
Jan 2021
Historique:
received:
04
03
2020
revised:
26
09
2020
accepted:
07
11
2020
pubmed:
28
11
2020
medline:
7
8
2021
entrez:
27
11
2020
Statut:
ppublish
Résumé
This study aimed to investigate the in vitro activity of taniborbactam (VNRX-5133), a novel broad-spectrum bicyclic boronate, against NDM-1 and Q119E, Q119K, Q119C, Q119F, Q119V, and Q119Y NDM-1 variants, which showed an increased activity towards some β-lactams, including cefepime. Inhibition kinetic assays were spectrophotometrically performed using cefepime (50 μM) as the reporter substrate and 80 nM of each enzyme. Taniborbactam behaves as a competitive inhibitor towards NDM-1 and NDM-1 Q119 variants with lower Ki values (range 3-16 nM). The phenotypic profile was assessed in both Enterobacterales clinical isolates and engineered Escherichia coli BL21(DE3) strains by conventional broth microdilution procedures according to the Clinical and Laboratory Standards Institute (CLSI). Taniborbactam at a fixed concentration of 4 mg/L was able to restore activity of cefepime in 24 of 26 Enterobacterales clinical isolates harbouring metallo-β-lactamases with MIC The inhibition level of NDM enzymes provided by taniborbactam protects the antibacterial activity of cefepime from this important metallo-β-lactamase.
Identifiants
pubmed: 33246038
pii: S0924-8579(20)30439-8
doi: 10.1016/j.ijantimicag.2020.106228
pii:
doi:
Substances chimiques
Anti-Bacterial Agents
0
Borinic Acids
0
Carboxylic Acids
0
beta-Lactamase Inhibitors
0
Cefepime
807PW4VQE3
taniborbactam
8IGQ156Z07
beta-Lactamases
EC 3.5.2.6
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
106228Informations de copyright
Copyright © 2020 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.