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，但生物学上的不确定性仍然存在并阻碍了进展。然而，由于包括学术界、制药行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优先考虑临床试验的多药治疗方案和改进试验设计以加速治疗方案开发并利用药物发现突破的固有挑战。最需要的是从潜伏感染到活动性肺部疾病进展的标志物、药物反应标志物和复发预测因素、揭示临床和动物模型协同作用的体外工具，以可靠地评估新疗法缩短治疗时间的潜力。在这篇综述中，我们从科学和操作的角度，强调了“一刀切”的治疗方案和治疗持续时间与基于疾病严重程度、宿主和病原体特征的个体化治疗的优点和挑战。