Risk of acquired drug resistance during short-course directly observed treatment of tuberculosis in an area with high levels of drug resistance
Risk of acquired drug resistance during short-course directly observed treatment of tuberculosis in an area with high levels of drug resistance
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DOI：
10.1086/517536
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发表时间：
2007-06-01
影响因子：
11.8
通讯作者：
Kebede, Yared
中科院分区：
文献类型：
--
作者：
Cox, Helen S.;Niemann, Stefan;Kebede, Yared
背景关于结核病标准化短程直接观察治疗（DOTS）在耐药性严重地区的效果以及DOTS对耐药性扩大的潜在影响的数据有限。因此，我们分析了在中亚乌兹别克斯坦和土库曼斯坦耐药水平高的地区参加DOTS项目的结核病患者的横断面样本的治疗结果。从8个区开始治疗的患者中获得痰液样本，用于检测对5种一线药物的敏感性和进行分子分型。在强化治疗期结束时和/或进入持续治疗期2个月时痰涂片结核阳性的患者再次进行检测。在382名诊断为结核病的患者中，62名对治疗反应不佳，再次检测时发现感染了相同的结核分枝杆菌菌株;其中19名患者的菌株产生了新的或额外的耐药性。在最初敏感或单一耐药结核菌株的患者中，仅1.2%发生扩增，但在诊断时，17%的多药耐药菌株（但不是多药耐药菌株，定义为至少对异烟肼和利福平耐药的菌株）和7%的多药耐药菌株患者中发生扩增。总体而言，3.5%最初未感染耐多药结核菌株的患者在治疗期间发展为耐多药结核菌株。而多重耐药的北京基因型菌株则表现为耐药扩增。在已确立的DOTS方案条件下，耐药性的高度扩增加强了在耐药性高的地区实施DOTS-Plus治疗耐多药结核病的必要性。北京基因型和扩增在先前存在的耐药性的情况下的强关联是惊人的，并且可能是该基因型和耐药性之间强关联的基础。
Background. Data on the performance of standardized short-course directly observed treatment (DOTS) of tuberculosis (TB) in areas with high levels of drug resistance and on the potential impact of DOTS on amplification of resistance are limited. Therefore, we analyzed treatment results from a cross-sectional sample of patients with TB enrolled in a DOTS program in an area with high levels of drug resistance in Uzbekistan and Turkmenistan in Central Asia.Methods. Sputum samples for testing for susceptibility to 5 first-line drugs and for molecular typing were obtained from patients starting treatment in 8 districts. Patients with sputum smear results positive for TB at the end of the intensive phase of treatment and/or at 2 months into the continuation phase were tested again.Results. Among 382 patients with diagnoses of TB, 62 did not respond well to treatment and were found to be infected with an identical Mycobacterium tuberculosis strain when tested again; 19 of these patients had strains that developed new or additional drug resistance. Amplification occurred in only 1.2% of patients with initially susceptible or monoresistant TB strains, but it occurred in 17% of those with polyresistant strains (but not multidrug-resistant strains, defined as strains with resistance to at least isoniazid and rifampicin) and in 7% of those with multidrug-resistant strains at diagnosis. Overall, 3.5% of the patients not initially infected with multidrug-resistant TB strains developed such strains during treatment. Amplification of resistance, however, was found only in polyresistant Beijing genotype strains.Conclusions. High levels of amplification of drug resistance demonstrated under well-established DOTS program conditions reinforce the need for implementation of DOTS-Plus for multidrug-resistant TB in areas with high levels of drug resistance. The strong association of Beijing genotype and amplification in situations of preexisting resistance is striking and may underlie the strong association between this genotype and drug resistance.