Division of Immunopathology and Cellular Immunology & Division of Microbiology, International Tuberculosis Research Center, Masan, Republic of Korea.
Department of Biomedical Laboratory Science, Yonsei University, Wonju, Republic of Korea.
Eur J Clin Microbiol Infect Dis. 2017 Nov;36(11):2063-2072. doi: 10.1007/s10096-017-3025-5. Epub 2017 Jun 15.
Mycobacterium tuberculosis (Mtb) in sputum originates from lung cavities in tuberculosis (TB) patients. But drug susceptibility testing (DST) of sputum Mtb can not be conducted the same as in the lung because mutagenesis of bacilli may be happening in the lung during treatment and result in the possibility of the presence of heterogeneous drug-resistant subpopulations in the different lung lesions. This could be one of the reasons for low cure rates for multi-drug resistant (MDR)-TB. We studied the resected lungs of nine surgery patients with chronic TB. The isolates isolated from the sputum and different lung lesions of each patient were tested for phenotypic DST and genotyped using restriction fragment length polymorphism (RFLP) typing method. Genetic analysis to resistance to first and second line drugs was also performed. Five of nine patients were MDR-TB and three XDR-TB. DST results for ten anti-TB drugs were in accordance among different lung lesions in eight patients. However, only three of these eight patients showed the concordance of DST with sputum. Even though the isolates were heteroresistant, genotyping them by RFLP showed the clonal population in each individual patient. Six of eight followed-up patients achieved successful cure. In conclusion, the heteroresistance between sputum and lung lesions and a clonal population without mixed infection might provide useful information in establishing treatment regimen and surgery decision for MDR- and XDR-TB.
结核分枝杆菌（Mtb）在痰液中来源于肺结核（TB）患者的肺部空洞。但是，由于在治疗过程中细菌可能会在肺部发生突变，导致不同肺部病变中可能存在异质性耐药亚群，因此不能像在肺部一样对痰液中的 Mtb 进行药敏试验（DST）。这可能是耐多药（MDR）-TB 治愈率低的原因之一。我们研究了 9 例慢性 TB 手术患者的切除肺。从每位患者的痰液和不同肺部病变中分离出的分离株，采用限制片段长度多态性（RFLP）分型方法进行表型 DST 检测和基因分型。还对一线和二线药物的耐药性进行了遗传分析。9 例患者中有 5 例为 MDR-TB，3 例为 XDR-TB。8 例患者的 10 种抗 TB 药物的 DST 结果在不同肺部病变中一致。然而，在这 8 例患者中，只有 3 例的痰液 DST 结果与之一致。即使分离株存在异质性耐药性，但通过 RFLP 对其进行基因分型显示了每个患者的克隆群体。8 例随访患者中有 6 例成功治愈。总之，痰液和肺部病变之间的异质性耐药性以及无混合感染的克隆群体可能为制定 MDR 和 XDR-TB 的治疗方案和手术决策提供有用信息。
