Characterization of Differentially Detectable Mycobacterium tuberculosis in the Sputum of Subjects with Drug-Sensitive or Drug-Resistant Tuberculosis before and after Two Months of Therapy.
Characterization of Differentially Detectable Mycobacterium tuberculosis in the Sputum of Subjects with Drug-Sensitive or Drug-Resistant Tuberculosis before and after Two Months of Therapy.
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DOI：
10.1128/aac.00608-21
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发表时间：
2021-07-16
影响因子：
4.9
通讯作者：
Fitzgerald DW
中科院分区：
文献类型：
--
作者：
Zainabadi K;Walsh KF;Vilbrun SC;Mathurin LD;Lee MH;Saito K;Mishra S;Ocheretina O;Pape JW;Nathan C;Fitzgerald DW
计数患者痰液中结核分枝杆菌的标准方法可能会遗漏大量的活菌群。结核病细胞不能在固体培养基或液体培养基中生长，除非培养基被广泛稀释。因为这些细菌可以在有限稀释后在液体培养基中检测到，所以它们被称为差异可培养的或差异可检测的M。结核病（DD-Mtb）。已显示用异烟肼（H）、利福平（R）、吡嗪酰胺（Z）和乙胺丁醇（E）（HRZE）治疗1至2周可增加药物敏感（DS）结核病（TB）患者痰中DD-Mtb的代表性。然而，在较长时间的HRZE治疗后或接受二线治疗的耐药（DR）TB患者中，对DD-Mtb知之甚少。在这里，我们测量了47例受试者（29例DS TB和18例DR TB）痰液中DD-Mtb细胞的比例，这些受试者在开始治疗前以及治疗后2周和2个月。在治疗前，DD-Mtb细胞代表了大多数M。21%的DS TB受试者的痰中存在结核细胞，一线药物治疗2周后这一比例上升至65%。在DR TB受试者中，治疗开始前在29%受试者的痰中发现DD-Mtb细胞，二线药物治疗2周后该比例稳定在31%。到2个月时，仅在2/15例（13.3%）DS TB受试者和0/15例DR TB受试者的痰液中检出DD-Mtb细胞。其中1例DS受试者在第2个月时痰液呈DD-Mtb阳性，随后发生治疗失败。
Standard methods for enumerating Mycobacterium tuberculosis in patient sputum can miss large populations of viable M. tuberculosis cells that are unable to grow either on solid medium or in liquid medium unless the medium has been extensively diluted. Because these bacteria can be detected in liquid medium after limiting dilution, they have been termed differentially culturable or differentially detectable M. tuberculosis (DD-Mtb). Treatment with isoniazid (H), rifampin (R), pyrazinamide (Z), and ethambutol (E) (HRZE) for 1 to 2 weeks has been shown to increase the representation of DD-Mtb in the sputum of drug-sensitive (DS) tuberculosis (TB) patients. However, little is known about DD-Mtb after longer periods of treatment with HRZE or in patients with drug-resistant (DR) TB who receive second-line therapies. Here, we measured the proportion of DD-Mtb cells in the sputum of 47 subjects, 29 with DS TB and 18 with DR TB, before initiation of treatment and at 2 weeks and 2 months thereafter. Prior to treatment, DD-Mtb cells represented the majority of M. tuberculosis cells in the sputum of 21% of subjects with DS TB, and this proportion rose to 65% after 2 weeks of treatment with first-line drugs. In subjects with DR TB, DD-Mtb cells were found in the sputum of 29% of subjects prior to treatment initiation, and this proportion remained steady at 31% after 2 weeks of treatment with second-line drugs. By 2 months, DD-Mtb cells were detected in the sputum of only 2/15 (13.3%) subjects with DS TB and in 0/15 of subjects with DR TB. One of the DS subjects whose sputum was positive for DD-Mtb at month 2 later experienced treatment failure.