Bacille Calmette-Guérin (BCG) is the only licenced tuberculosis (TB) vaccine, but has limited efficacy against pulmonary TB disease development and modest protection against extrapulmonary TB. Preventative antibiotic treatment for Mycobacterium tuberculosis (Mtb) infections in high-prevalence settings is unfeasible due to unclear treatment durability, drug toxicity, logistical constraints related to directly observed treatment strategy (DOTS) and the lengthy treatment protocols. Together, these factors promote non-adherence, contributing to relapse and establishment of drug-resistant Mtb strains. Although antibiotic treatment of drug-susceptible Mtb is generally effective, drug-resistant TB has a treatment efficacy below 50% and can, in a proportion, develop into progressive, untreatable disease. Other immune compromising co-infections and/or co-morbidities require more complex prevention/treatment approaches, posing huge financial burdens to national health services. Novel TB treatment strategies, such as host-directed therapeutics, are required to complement pathogen-targeted approaches. Pre-clinical studies have highlighted promising candidates that enhance endogenous pathways and/or limit destructive host responses. This review discusses promising pre-clinical candidates and forerunning compounds at advanced stages of clinical investigation in TB host-directed therapeutic (HDT) efficacy trials. Such approaches are rationalized to improve outcome in TB and shorten treatment strategies.

卡介苗 (BCG) 是唯一获得许可的结核病 (TB) 疫苗，但对肺结核病发展的疗效有限，对肺外结核的保护作用有限。由于不明确的治疗持久性、药物毒性、与直接观察治疗策略 (DOTS) 相关的后勤限制以及冗长的治疗方案，在高流行环境中对结核分枝杆菌( Mtb ) 感染进行预防性抗生素治疗是不可行的。这些因素共同促进了非依从性，导致复发和耐药Mtb菌株的建立。尽管对药物敏感的Mtb进行了抗生素治疗一般有效，耐药结核病的治疗有效率低于 50%，并且在一定程度上可以发展为进行性的、无法治愈的疾病。其他免疫受损的合并感染和/或合并症需要更复杂的预防/治疗方法，给国家卫生服务带来巨大的财政负担。需要新的结核病治疗策略，例如宿主导向疗法，以补充病原体靶向方法。临床前研究突出了有前途的候选药物，它们可以增强内源性途径和/或限制破坏性宿主反应。这篇综述讨论了在 TB 宿主导向治疗 (HDT) 疗效试验中处于临床研究晚期的有前途的临床前候选化合物和先行化合物。这些方法被合理化以改善结核病的结果并缩短治疗策略。