Reinfection and mixed infection cause changing Mycobacterium tuberculosis drug-resistance patterns
Reinfection and mixed infection cause changing Mycobacterium tuberculosis drug-resistance patterns
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DOI：
10.1164/rccm.200503-449oc
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发表时间：
2005-09-01
影响因子：
24.7
通讯作者：
Warren, RM
中科院分区：
文献类型：
--
作者：
van Rie, A;Victor, TC;Warren, RM
基本原理：在感染压力高的环境中，可能会发生不同菌株结核分枝杆菌的多重感染。混合感染与患者、临床医生和控制程序的相关性仍不清楚。目的：本研究旨在将再感染和混合感染描述为改变连续痰培养药敏模式的潜在机制。方法：采用表型药敏试验和突变检测方法对确诊为多药耐药(MDR)肺结核患者的痰标本进行连续培养。采用IS6110 DNA指纹图谱和一种新的菌株特异性聚合酶链式反应扩增方法进行基因分型。检测方法及主要结果：48例耐多药肺结核患者连续痰培养DNA指纹分析，其中10例为再感染，1例为混合感染。而菌株特异性聚合酶链式反应扩增分析显示，11例中有9例S混合感染，3例再感染，1例实验室污染。对临床数据的分析表明，一线治疗可以选择耐药亚群，而不良的依从性或二线治疗会导致药物敏感亚群的重新出现。结论：我们已经证明，在一些耐多药结核病患者中，混合感染可能是通过DNA指纹图谱观察到的再感染的原因。我们的结论是，治疗和粘附性决定了哪种菌株是优势菌株。我们假设，二线药物治疗可能会导致混合感染患者中药物敏感菌株的重新出现。
Rationale: Multiple infections with different strains of Mycobacterium tuberculosis may occur in settings where the infection pressure is high. The relevance of mixed infections for the patient, clinician, and control program remains unclear. Objectives: This study aimed to describe reinfection and mixed infection as underlying mechanisms of changing drug-susceptibility patterns in serial sputum cultures. Methods: Serial M. tuberculosis sputum cultures from patients diagnosed with multi-drug-resistant (MDR) tuberculosis were evaluated by phenotypic drug-susceptibility testing and mutation detection methods. Genotypic analysis was done by IS6110 DNA fingerprinting and a novel strain-specific polymerase chain reaction amplification method. Measurements and Main Results: DNA fingerprinting analysis of serial sputum cultures from 48 patients with MDR tuberculosis attributed 10 cases to reinfection and I case to mixed infection. In contrast, strain-specific polymerase chain reaction amplification analysis in 9 of the 11 cases demonstrated mixed infection in S cases, reinfection in 3 cases, and laboratory contamination in I case. Analysis of clinical data suggests that first-line therapy can select for a resistant subpopulation, whereas poor adherence or second-line therapy resulted in the reemergence of the drug-susceptible subpopulations. Conclusions: We have shown that, in some patients with MDR tuberculosis, mixed infection may be responsible for observations attributed to reinfection by DNA fingerprinting. We conclude that treatment and adherence determines which strain is dominant. We hypothesize that treatment with second-line drugs may lead to reemergence of the drug-susceptible strain in patients with mixed infection.