Rationale: Earlier biomarkers of pulmonary tuberculosis (PTB) treatment outcomes are critical to monitor shortened anti-TB treatment (ATT). Objectives: To identify early microbiologic markers of unfavorable TB treatment outcomes. Methods: We performed a subanalysis of 2 prospective TB cohort studies conducted from 2013 to 2019 in India. We included participants aged ⩾18 years who initiated 6-month ATT for clinically or microbiologically diagnosed drug-sensitive PTB and completed at least one follow-up visit. Sputum specimens were subjected to a baseline Xpert Mycobacterium tuberculosis/rifampin (MTB/RIF) assay, acid-fast bacilli (AFB) microscopy and liquid and solid cultures, and serial AFB microscopy and liquid and solid cultures at weeks 2, 4, and 8. Poisson regression was used to assess the impact of available microbiologic markers (test positivity, smear grade, time to detection, and time to conversion) on a composite outcome of failure, recurrence, or death by 18 months after the end of treatment. Models were adjusted for age, sex, nutritional status, diabetes, smoking, alcohol consumption, and regimen type. Results: Among 1,098 eligible cases, there were 251 (22%) adverse TB treatment outcomes: 127 (51%) treatment failures, 73 (29%) recurrences, and 51 (20%) deaths. The primary outcome was independently associated with the Xpert MTB/RIF assay (medium-positive adjusted incidence rate ratio [aIRR], 1.91; 95% confidence interval [CI], 1.07-3.40; high-positive aIRR, 2.51; 95% CI, 1.41-4.46), positive AFB smear (aIRR, 1.48; 95% CI, 1.06-2.06), and positive liquid culture (aIRR, 1.98; 95% CI, 1.21-3.23) at baseline; Week 2 positive liquid culture (aIRR, 1.47; 95% CI, 1.04-2.09); and Week 8 positive AFB smear (aIRR, 1.63; 95% CI, 1.06-2.50) and positive liquid culture (aIRR, 1.54; 95% CI, 1.07-2.22). There was no evidence of Mycobacterium tuberculosis growth in the Mycobacterium Growth Indicator Tube at Week 4 conferring a higher risk of adverse outcomes (aIRR, 1.25; 95% CI, 0.89-1.75). Conclusions: Our analysis identifies Week 2 respiratory mycobacterial culture as the earliest microbiologic marker of unfavorable PTB treatment outcomes.

中文翻译：

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肺结核治疗结果的早期微生物标志物。

理由：肺结核 (PTB) 治疗结果的早期生物标志物对于监测缩短的抗结核治疗 (ATT) 至关重要。目的：确定不良结核病治疗结果的早期微生物标志物。方法：我们对 2013 年至 2019 年在印度进行的 2 项前瞻性结核病队列研究进行了亚分析。我们纳入了年龄⩾18岁的参与者，他们针对临床或微生物学诊断的药物敏感PTB开始了6个月的ATT，并完成了至少一次随访。对痰标本进行基线 Xpert 结核分枝杆菌/利福平 (MTB/RIF) 测定、抗酸杆菌 (AFB) 显微镜检查和液体和固体培养，以及在第 2、4 和 8 周进行连续 AFB 显微镜检查以及液体和固体培养泊松回归用于评估现有微生物标志物（检测阳性、涂片分级、检测时间和转化时间）对治疗结束后 18 个月内失败、复发或死亡的综合结果的影响。模型根据年龄、性别、营养状况、糖尿病、吸烟、饮酒和养生方式进行了调整。结果：在 1,098 例符合条件的病例中，有 251 例（22%）结核病治疗结果不良：127 例（51%）治疗失败，73 例（29%）复发，51 例（20%）死亡。主要结局与 Xpert MTB/RIF 检测独立相关（中阳性调整后发生率比 [aIRR]，1.91；95% 置信区间 [CI]，1.07-3.40；高阳性 aIRR，2.51；95% CI，基线时 AFB 涂片阳性（aIRR，1.41-4.46）、阳性（aIRR，1.48；95% CI，1.06-2.06）和液体培养阳性（aIRR，1.98；95% CI，1.21-3.23）；第 2 周液体培养阳性（aIRR，1.47；95% CI，1.04-2.09）；第 8 周 AFB 涂片阳性（aIRR，1.63；95% CI，1.06-2.50）和液体培养阳性（aIRR，1.54；95% CI，1.07-2.22）。没有证据表明第 4 周时分枝杆菌生长指示管中结核分枝杆菌的生长会带来较高的不良结果风险（aIRR，1.25；95% CI，0.89-1.75）。结论：我们的分析确定第 2 周呼吸道分枝杆菌培养物是不良 PTB 治疗结果的最早微生物标志物。