Kayigire Xavier A, Friedrich Sven O, van der Merwe Lize, Diacon Andreas H
Division of Molecular Biology and Human Genetics, MRC Centre for Tuberculosis Research, DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa.
Task Applied Science, Bellville, Cape Town, South Africa.
Antimicrob Agents Chemother. 2017 Mar 24;61(4). doi: 10.1128/AAC.02220-16. Print 2017 Apr.
strains with spontaneous mutations conferring resistance to rifampin (RIF) are exceedingly rare, and fixed drug combinations typically prevent augmentation of resistance to single drugs. Fourteen newly diagnosed tuberculosis patients were treated with RIF alone for 14 days, and bacterial loads, including mutation frequencies, were determined. A statistical model estimated that 1% of the remaining viable mycobacteria could be RIF resistant after 30 days of monotherapy. This indicates that temporal and spatial windows of RIF monotherapy due to uneven drug distribution within lung lesions could contribute to the acquisition of resistance to RIF.
具有对利福平（RIF）耐药的自发突变菌株极为罕见，而固定的药物组合通常可防止对单一药物的耐药性增加。对14例新诊断的结核病患者单独使用利福平治疗14天，并测定细菌载量，包括突变频率。一个统计模型估计，单药治疗30天后，剩余存活分枝杆菌中有1%可能对利福平耐药。这表明，由于肺部病变内药物分布不均，利福平单药治疗的时间和空间窗口可能导致对利福平耐药性的产生。
