Mechanisms of heteroresistance to isoniazid and rifampin of Mycobacterium tuberculosis in Tashkent, Uzbekistan
Mechanisms of heteroresistance to isoniazid and rifampin of Mycobacterium tuberculosis in Tashkent, Uzbekistan
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DOI：
10.1183/09031936.00089808
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发表时间：
2009-02-01
影响因子：
24.3
通讯作者：
Hoffmann, H.
中科院分区：
文献类型：
--
作者：
Hofmann-Thiel, S.;van Ingen, J.;Hoffmann, H.
结核分枝杆菌（MTB）异质耐药性定义为同一患者体内同时存在抗结核（TB）药物的敏感菌和耐药菌。 MTB的异抗性被认为是完全抗性的初级阶段。迄今为止，尚未证实导致 MTB 异质耐药的机制。使用 Genotype MTBDR 测定（Hain Lifescience，Nehren，德国）对来自乌兹别克斯坦塔什干的 35 名结核病患者的临床标本和培养物进行了分析，该测定旨在检测与利福平和异烟肼耐药相关的基因突变。使用分枝杆菌散布重复单元变量串联重复分型、spoligotyping和IS6110指纹图谱对异质耐药病例进一步进行基因分型。7例（20%）发现对利福平和/或异烟肼异质耐药。其中五个菌株的异质抗性是由两种不同的菌株引起的，另外两个菌株的异质抗性是由北京基因型的单一菌株引起的。后者有结核病复发史。首次使用逐步分子生物学方法证明了结核病异质耐药的两种不同机制：1）两种不同菌株的重复感染，这引起了临床感染控制从业者的兴趣； 2) 将单一菌株分裂为敏感和抗性生物体。后一种机制很可能与治疗质量差有关，并且可以作为未来结核病治疗计划的质量标志。
Heteroresistance of Mycobacterium tuberculosis (MTB) is defined as the coexistence of susceptible and resistant organisms to anti-tuberculosis (TB) drugs in the same patient. Heteroresistance of MTB is considered a preliminary stage to full resistance. To date, no mechanism causing heteroresistance of MTB has been proven.Clinical specimens and cultures from 35 TB patients from Tashkent, Uzbekistan, were analysed using the Genotype MTBDR assay (Hain Lifescience, Nehren, Germany), which is designed to detect genetic mutations associated with resistance to rifampin and isoniazid. Cases of heteroresistance were further subjected to genotyping using mycobacterial interspersed repetitive unit-variable-number tandem repeat typing, spoligotyping and IS6110 fingerprinting.Heteroresistance to rifampin and/or isoniazid was found in seven cases (20%). In five of them, heteroresistance was caused by two different strains and in two by a single strain of the Beijing genotype. The latter cases had a history of relapse of their TB.For the first time, two different mechanisms of heteroresistance in tuberculosis have been proven using a stepwise molecular-biological approach: 1) superinfection with two different strains, which is of interest for clinical infection control practitioners; and 2) splitting of a single strain into susceptible and resistant organisms. The latter mechanism is most likely to be related to poor treatment quality and could serve as a quality marker for tuberculosis therapy programmes in the future.