DiNardo Andrew R, Sabiiti Wilbert, Gillespie Stephen H, Georghiou Sophia B, Heinrich Norbert, Hittel Norbert, Taghlabi Sami, Carrero Longlax Danna, Kohli Mikashmi, Panzner Ursula, Musia Collins, Lange Christoph, Vasiliu Anca, Arts Rob J W, Mandalakas Anna M, Ruhwald Morten, Stuyver Lieven J, van Crevel Reinout
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.
The Global Tuberculosis Program, Texas Children's Hospital, Department of Pediatrics, Baylor College of Medicine, Houston, TX, United States.
Front Antibiot. 2025 May 22;4:1570989. doi: 10.3389/frabi.2025.1570989. eCollection 2025.
Tuberculosis drug trials are primarily designed to identify antibiotic regimens with the strongest potency to kill . However, microbiologic cure is not synonymous with improved health and recovery. Beyond antimicrobial efficacy, parameters such as morbidity and mortality related to lung function, cardiovascular health, and cancer should be prioritized. This narrative review emphasizes the critical need to emphasize clinical outcomes as much, if not more, than microbiological endpoints. We examine the underlying pathophysiological mechanisms and determinants of non-microbiological outcomes in tuberculosis, providing a synthesis of current knowledge. While there is growing evidence for some biomarkers to risk stratify TB patients for risk of all-cause mortality, relapse, or lung damage, no evidence was found on TB-associated cancer or cardiovascular disease. In addition to monitoring microbiologic outcomes, clinical trials and treatment cohorts need to capture patient-centered health dimensions more broadly. Finally, we highlight key research gaps and opportunities to evaluate non-microbiological biomarkers, aiming to improve patient monitoring and enable stratified approaches to tuberculosis management.
结核病药物试验主要旨在确定具有最强杀菌效力的抗生素治疗方案。然而，微生物学治愈并不等同于健康状况改善和康复。除了抗菌疗效外，还应优先考虑与肺功能、心血管健康和癌症相关的发病率和死亡率等参数。这篇叙述性综述强调了与微生物学终点同样甚至更强调临床结局的迫切需求。我们研究了结核病中非微生物学结局的潜在病理生理机制和决定因素，对当前知识进行了综合。虽然越来越多的证据表明某些生物标志物可对结核病患者的全因死亡率、复发或肺损伤风险进行风险分层，但未发现与结核病相关的癌症或心血管疾病的相关证据。除了监测微生物学结局外，临床试验和治疗队列还需要更广泛地获取以患者为中心的健康维度信息。最后，我们强调了评估非微生物学生物标志物的关键研究差距和机会，旨在改善患者监测并实现结核病管理的分层方法。
