Sun Qingfeng, Li Shanshan, Gao Mengqiu, Pang Yu
Department of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China;The Second Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China.
Department of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China.
Biomed Environ Sci. 2024 Nov 20;37(11):1310-1323. doi: 10.3967/bes2024.168.
Tuberculosis (TB) remains a significant global health challenge, ranking second only to COVID-19 as the leading cause of death from a single infectious agent, with 1.3 million TB-related deaths reported in 2022. Treatment efficacy has been compromised by the emergence of drug-resistant strains, including rifampin-resistant TB (RR-TB), multidrug-resistant TB (MDR-TB), and extensively drug-resistant TB (XDR-TB). Although first-line drugs like isoniazid, rifampicin, pyrazinamide, and ethambutol form the cornerstone of TB therapy, the rise of resistant strains necessitates the use of second-line drugs, which often come with increased toxicity and limited accessibility. Recent advances have focused on repurposing existing compounds and developing new drugs with novel mechanisms of action. Promising agents such as second-generation bedaquiline analogs (TBAJ-587, TBAJ-876), sudapyridine (WX-081), delamanid, pretomanid, and TBI-166 (pyrifazimine) have shown efficacy against resistant Mtb strains. Innovative treatment regimens like the BPaLM protocol-combining bedaquiline, pretomanid, linezolid, and moxifloxacin-offer shorter, all-oral therapies with higher cure rates. Personalized treatment durations and dose optimizations are becoming feasible through risk stratification algorithms and pharmacokinetic/pharmacodynamic studies. Immunotherapy is emerging as a complementary strategy to enhance the host's immune response against Mtb. Agents such as vitamin D, corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), statins, metformin, and biological agents like interleukins and granulocyte-macrophage colony-stimulating factor are under exploration. Additionally, cell therapies involving mesenchymal stem cells and immune effector cells present new therapeutic avenues. Despite these advancements, significant challenges remain in achieving the World Health Organization's "End TB Strategy" goals, particularly as the COVID-19 pandemic has diverted resources and attention. Ongoing research and global collaboration are crucial to develop novel therapeutic strategies, optimize treatment regimens, and ultimately reduce the global burden of TB.
结核病仍然是一项重大的全球卫生挑战，作为单一传染源导致死亡的主要原因，仅次于新冠病毒，2022年报告有130万例与结核病相关的死亡。耐药菌株的出现，包括耐利福平结核病（RR-TB）、耐多药结核病（MDR-TB）和广泛耐药结核病（XDR-TB），损害了治疗效果。虽然异烟肼、利福平、吡嗪酰胺和乙胺丁醇等一线药物构成了结核病治疗的基石，但耐药菌株的增加使得必须使用二线药物，而二线药物往往毒性更大且可及性有限。最近的进展集中在对现有化合物进行重新利用以及开发具有新作用机制的新药。第二代贝达喹啉类似物（TBAJ-587、TBAJ-876）、舒达吡啶（WX-081）、德拉马尼、普瑞玛尼和TBI-166（吡啶嗪胺）等有前景的药物已显示出对耐药结核分枝杆菌菌株的疗效。像BPaLM方案（联合贝达喹啉、普瑞玛尼、利奈唑胺和莫西沙星）这样的创新治疗方案提供了疗程更短的全口服疗法，治愈率更高。通过风险分层算法以及药代动力学/药效学研究，个性化的治疗疗程和剂量优化正变得可行。免疫疗法正在成为一种补充策略，以增强宿主对结核分枝杆菌的免疫反应。维生素D、皮质类固醇、非甾体抗炎药（NSAIDs）、他汀类药物、二甲双胍以及白细胞介素和粒细胞-巨噬细胞集落刺激因子等生物制剂正在探索中。此外，涉及间充质干细胞和免疫效应细胞的细胞疗法提供了新的治疗途径。尽管有这些进展，但在实现世界卫生组织的“终止结核病战略”目标方面仍存在重大挑战，特别是新冠疫情转移了资源和注意力。持续的研究和全球合作对于开发新治疗策略、优化治疗方案以及最终减轻全球结核病负担至关重要。
