Unit of Mycobacteriology, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa (IHMT/UNL), Rua da Junqueira, Lisbon, Portugal.
Expert Rev Anti Infect Ther. 2010 Apr;8(4):465-80. doi: 10.1586/eri.10.20.
Tuberculosis (TB) is mainly an intracellular infection of the lung alveolar macrophages, and any anti-TB agent must therefore be active at the macrophage. Among the available therapies, isoniazid and rifampicin are the most effective drugs against susceptible Mycobacterium tuberculosis, but they are ineffective against multidrug-resistant TB (MDRTB) strains. Rates of MDRTB in Portugal are the highest in Western Europe, demanding effective measures for their control. Our application of molecular techniques for the early identification of MDRTB assisted in the reduction of these rates. Further examination revealed that a large number of MDRTB cases were extensively-drug resistant (XDRTB), providing evidence for the urgent need of new and effective anti-MDRTB/XDRTB therapeutic strategies. This review describes in detail: the characteristics of the main M. tuberculosis strains circulating in Portugal; the creation of a Task Force for TB control, based on molecular tools that allow 1-day identification of an MDRTB patient; the usefulness of evaluating the ex vivo activity of anti-tubercular agents against the M. tuberculosis isolated from the patient's sputum; and the mode of action by which phenothiazines have been shown to promote the killing of intracellular MDRTB/XDRTB by nonkilling macrophages.
肺结核（TB）主要是肺肺泡巨噬细胞的细胞内感染，因此任何抗结核药物都必须在巨噬细胞中发挥作用。在现有的治疗方法中，异烟肼和利福平是针对敏感结核分枝杆菌最有效的药物，但对耐多药结核（MDRTB）菌株无效。葡萄牙的 MDRTB 发病率在西欧是最高的，需要采取有效措施加以控制。我们应用分子技术早期鉴定 MDRTB，有助于降低这些发病率。进一步的检查表明，大量 MDRTB 病例为广泛耐药（XDRTB），这为迫切需要新的和有效的抗 MDRTB/XDRTB 治疗策略提供了证据。本综述详细描述了：在葡萄牙流行的主要结核分枝杆菌菌株的特征；创建了一个基于分子工具的结核病控制特别工作组，该工作组可在 1 天内鉴定出 MDRTB 患者；评估抗结核药物对从患者痰液中分离出的结核分枝杆菌的体外活性的有用性；以及苯并嗪类药物通过非致死性巨噬细胞促进细胞内 MDRTB/XDRTB 杀伤的作用方式。
