Despite two decades of intensified research to understand and cure tuberculosis disease, biological uncertainties remain and hamper progress. However, owing to collaborative initiatives including academia, the pharmaceutical industry and non-for-profit organizations, the drug candidate pipeline is promising. This exceptional success comes with the inherent challenge of prioritizing multidrug regimens for clinical trials and revamping trial designs to accelerate regimen development and capitalize on drug discovery breakthroughs. Most wanted are markers of progression from latent infection to active pulmonary disease, markers of drug response and predictors of relapse, in vitro tools to uncover synergies that translate clinically and animal models to reliably assess the treatment shortening potential of new regimens. In this Review, we highlight the benefits and challenges of ‘one-size-fits-all’ regimens and treatment duration versus individualized therapy based on disease severity and host and pathogen characteristics, considering scientific and operational perspectives.

尽管为了解和治愈结核病进行了二十年的深入研究，但生物学的不确定性仍然存在并阻碍了进展。然而，由于包括学术界、制药业和非营利组织在内的合作倡议，候选药物管道前景广阔。这一非凡的成功伴随着固有的挑战，即为临床试验确定多药治疗方案的优先级并改进试验设计以加速治疗方案开发并利用药物发现突破。最需要的是从潜伏感染进展为活动性肺部疾病的标志物、药物反应的标志物和复发的预测因子、用于发现转化为临床转化的协同作用的体外工具和用于可靠地评估新方案的治疗缩短潜力的动物模型。在这篇评论中，