Sub-MIC levels of bedaquiline and clofazimine can select Mycobacterium tuberculosis mutants with increased MIC

被引：0
|
作者：
Villellas, Cristina [1 ]
Stevenaert, Frederik [1 ,2 ]
Remmerie, Bart [1 ]
Andries, Koen [1 ]
机构：
[1] Janssen Res & Dev, Beerse, Belgium
[2] Aelin Therapeut, Leuven, Belgium
来源：
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY | 2024年 / 68卷 / 04期
关键词：
bedaquiline; tuberculosis; drug resistance; clofazimine; Rv0678; DRUG-RESISTANT TUBERCULOSIS; PHARMACOKINETICS;
D O I：
10.1128/aac.01275-23
中图分类号：
Q93 [微生物学];
学科分类号：
071005 ; 100705 ;
摘要：
Multidrug-resistant tuberculosis (MDR-TB) patients not cured at the time of stopping treatment are exposed to Minimum Inhibitory Concentration (MIC) and sub-MIC levels for many months after discontinuing bedaquiline (BDQ) or clofazimine (CFZ) treatment. In vitro cultures treated with BDQ and CFZ sub-MIC concentrations clearly showed enrichment in the Rv0678 mutant population, demonstrating that pre-existing Rv0678 mutants can be selected by sub-MIC concentrations of BDQ and CFZ if not protected by an alternative MDR-TB treatment.
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