In Vitro Activity of ß-Lactams in Combination with ß-Lactamase Inhibitors against Mycobacterium tuberculosis Clinical Isolates.
Biomed Res Int
; 2018: 3579832, 2018.
Article
en En
| MEDLINE
| ID: mdl-30065936
ABSTRACT
OBJECTIVES:
Evaluating the activity of nineteen ß-lactams in combination with different ß-lactamase inhibitors to determine the most potent combination against Mycobacterium tuberculosis (MTB) in vitro.METHODS:
Drug activity was examined by drug susceptibility test with 122 clinical isolates from China. Mutations of blaC and drug targets ldtMt1 , ldtMt2 , dacB2, and crfA were analyzed by nucleotide sequencing.RESULTS:
Tebipenem (TBM) in combination with clavulanate (CLA) exhibited the highest anti-TB activity. The MIC of ß-lactam antibiotics was reduced most evidently in the presence of CLA, compared to avibactam (AVI) and sulbactam (SUB). Eight polymorphism sites were identified in blaC, which were not associated with ß-lactams resistance. Interestingly, one strain carrying G514A mutation in blaC was highly susceptible to ß-lactams regardless of the presence of inhibitors. The transpeptidase encoding genes, ldtMt1 , ldtMt2 , and dacB2, harboured three mutations, two mutations, and one mutation, respectively, but no correlation was found between these mutations and drug resistance.CONCLUSION:
The activity of ß-lactams against MTB and different synergetic effect of ß-lactamase inhibitors were indicated. TBM/CLA exhibited the most activity and has a great prospect in developing novel anti-TB regimen; however, further clinical research is warranted. Moreover, the resistance to the ß-lactam antibiotics might not be conferred by single target mutation in MTB and requires further studies.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Beta-Lactamas
/
Inhibidores de beta-Lactamasas
/
Mycobacterium tuberculosis
País/Región como asunto:
Asia
Idioma:
En
Revista:
Biomed Res Int
Año:
2018
Tipo del documento:
Article
País de afiliación:
China