Moore David A J, Evans Carlton A W, Gilman Robert H, Caviedes Luz, Coronel Jorge, Vivar Aldo, Sanchez Eduardo, Piñedo Yvette, Saravia Juan Carlos, Salazar Cayo, Oberhelman Richard, Hollm-Delgado Maria-Graciela, LaChira Doris, Escombe A Roderick, Friedland Jon S
Department of Infectious Diseases and Immunity and the Wellcome Centre for Clinical Tropical Medicine, Imperial College London, Faculty of Medicine (Hammersmith Campus), London, United Kingdom.
N Engl J Med. 2006 Oct 12;355(15):1539-50. doi: 10.1056/NEJMoa055524.
New diagnostic tools are urgently needed to interrupt the transmission of tuberculosis and multidrug-resistant tuberculosis. Rapid, sensitive detection of tuberculosis and multidrug-resistant tuberculosis in sputum has been demonstrated in proof-of-principle studies of the microscopic-observation drug-susceptibility (MODS) assay, in which broth cultures are examined microscopically to detect characteristic growth.
In an operational setting in Peru, we investigated the performance of the MODS assay for culture and drug-susceptibility testing in three target groups: unselected patients with suspected tuberculosis, prescreened patients at high risk for tuberculosis or multidrug-resistant tuberculosis, and unselected hospitalized patients infected with the human immunodeficiency virus. We compared the MODS assay head-to-head with two reference methods: automated mycobacterial culture and culture on Löwenstein-Jensen medium with the proportion method.
Of 3760 sputum samples, 401 (10.7%) yielded cultures positive for Mycobacterium tuberculosis. Sensitivity of detection was 97.8% for MODS culture, 89.0% for automated mycobacterial culture, and 84.0% for Löwenstein-Jensen culture (P<0.001); the median time to culture positivity was 7 days, 13 days, and 26 days, respectively (P<0.001), and the median time to the results of susceptibility tests was 7 days, 22 days, and 68 days, respectively. The incremental benefit of a second MODS culture was minimal, particularly in patients at high risk for tuberculosis or multidrug-resistant tuberculosis. Agreement between MODS and the reference standard for susceptibility was 100% for rifampin, 97% for isoniazid, 99% for rifampin and isoniazid (combined results for multidrug resistance), 95% for ethambutol, and 92% for streptomycin (kappa values, 1.0, 0.89, 0.93, 0.71, and 0.72, respectively).
A single MODS culture of a sputum sample offers more rapid and sensitive detection of tuberculosis and multidrug-resistant tuberculosis than the existing gold-standard methods used.
迫切需要新的诊断工具来阻断结核病和耐多药结核病的传播。在显微镜观察药物敏感性（MODS）检测的原理验证研究中，已证实可对痰液中的结核病和耐多药结核病进行快速、灵敏的检测，该检测通过显微镜检查肉汤培养物以检测特征性生长。
在秘鲁的实际工作环境中，我们调查了MODS检测在三个目标群体中用于培养和药敏试验的性能：未经过筛选的疑似结核病患者、预先筛选出的结核病或耐多药结核病高危患者，以及未经过筛选的感染人类免疫缺陷病毒的住院患者。我们将MODS检测与两种参考方法进行了直接比较：自动分枝杆菌培养和采用比例法在罗-琴培养基上培养。
在3760份痰液样本中，401份（10.7%）培养出结核分枝杆菌阳性。MODS培养的检测灵敏度为97.8%，自动分枝杆菌培养为89.0%，罗-琴培养为84.0%（P<0.001）；培养呈阳性的中位时间分别为7天、13天和26天（P<0.001），药敏试验结果的中位时间分别为7天、22天和68天。第二次MODS培养的额外益处极小，尤其是在结核病或耐多药结核病高危患者中。MODS与药敏参考标准之间的一致性：利福平为100%，异烟肼为97%，利福平和异烟肼（耐多药综合结果）为99%，乙胺丁醇为95%，链霉素为92%（kappa值分别为1.0、0.89、0.93、0.71和0.72）。
痰液样本的单次MODS培养比现有的金标准方法能更快速、灵敏地检测结核病和耐多药结核病。
