Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Tuberculosis (Edinb). 2010 Mar;90(2):152-7. doi: 10.1016/j.tube.2010.01.001. Epub 2010 Jan 25.
Rifampin is a key component of standard short-course first-line therapy against Mycobacterium tuberculosis (MTB). Rifampin monoresistant MTB, previously a rare phenomenon, is now being reported at increasing rates worldwide. We report a mutation in the rpoB region leading to low level rifampin monoresistance in a cluster of HIV-positive patients. All rifampin monoresistant isolates identified from 2004 to 2006 underwent susceptibility confirmation, sequencing of rpoB and genotyping. Three patients were found to have a previously undocumented 3 base pair insertion at codon 525 in the rpoB region. The earliest initial case was infected with fully susceptible MTB. Disease relapse occurred 7 months later with a genotypically identical MTB isolate, showing acquired rifampin monoresistance. MTB isolates from 2 subsequent patients showed primary rifampin monoresistance with an identical genotype to the index case. Patients with rifampin monoresistant MTB tend to have poorer outcomes than those with fully susceptible strains. Risk factors for the development of rifampin monoresistance include co-morbid HIV infection and previously treated tuberculosis. HIV infection has been associated with malabsorption of anti-tuberculous medications leading to sub-therapeutic levels of administered drugs. These factors may have played a role in the development of this previously undocumented mutation.
利福平是治疗结核分枝杆菌（MTB）的标准短程一线疗法的关键组成部分。利福平单耐药 MTB 以前是一种罕见现象，现在在全球范围内的报告率正在上升。我们报告了一组 HIV 阳性患者中 rpoB 区域的突变导致低水平利福平单耐药。2004 年至 2006 年间鉴定的所有利福平单耐药分离株均进行了药敏确认、rpoB 测序和基因分型。发现 3 例患者在 rpoB 区域的密码子 525 处有 3 个碱基的插入，这是以前未记录过的。最早的初始病例感染了完全敏感的 MTB。7 个月后，疾病复发，分离出基因型完全相同的耐利福平 MTB，表明获得性利福平单耐药。随后 2 例患者的 MTB 分离株显示出与指数病例相同的基因型的原发性利福平单耐药。利福平单耐药 MTB 的患者比完全敏感株的患者预后更差。利福平单耐药的发展的危险因素包括合并 HIV 感染和既往治疗过的结核病。HIV 感染与抗结核药物吸收不良有关，导致给予药物的治疗水平降低。这些因素可能在这种以前未记录的突变的发展中起了作用。
