Frontiers in Antibiotics (May 2025)
Inclusion of patient-centered, non-microbiological endpoints and biomarkers in tuberculosis drug trials
- Andrew R. DiNardo,
- Andrew R. DiNardo,
- Wilbert Sabiiti,
- Stephen H. Gillespie,
- Sophia B. Georghiou,
- Norbert Heinrich,
- Norbert Heinrich,
- Norbert Hittel,
- Sami Taghlabi,
- Danna Carrero Longlax,
- Mikashmi Kohli,
- Ursula Panzner,
- Ursula Panzner,
- Collins Musia,
- Christoph Lange,
- Christoph Lange,
- Christoph Lange,
- Christoph Lange,
- Anca Vasiliu,
- Anca Vasiliu,
- Anca Vasiliu,
- Rob J. W. Arts,
- Anna M. Mandalakas,
- Anna M. Mandalakas,
- Anna M. Mandalakas,
- Morten Ruhwald,
- Lieven J. Stuyver,
- Reinout van Crevel,
- Reinout van Crevel
Affiliations
- Andrew R. DiNardo
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
- Andrew R. DiNardo
- The Global Tuberculosis Program, Texas Children’s Hospital, Department of Pediatrics, Baylor College of Medicine, Houston, TX, United States
- Wilbert Sabiiti
- Division of Infectious Disease and Global Health, University of St Andrews, St Andrews, United Kingdom
- Stephen H. Gillespie
- Division of Infectious Disease and Global Health, University of St Andrews, St Andrews, United Kingdom
- Sophia B. Georghiou
- FIND, Geneva, Switzerland
- Norbert Heinrich
- Division of Infectious Diseases and Tropical Medicine, LMU University Hospital, Munich, Germany
- Norbert Heinrich
- German Center for Infection Research (DZIF), Partner Site Munich, Munich, Germany
- Norbert Hittel
- Otsuka Novel Products GmbH, Munich, Germany
- Sami Taghlabi
- The Global Tuberculosis Program, Texas Children’s Hospital, Department of Pediatrics, Baylor College of Medicine, Houston, TX, United States
- Danna Carrero Longlax
- The Global Tuberculosis Program, Texas Children’s Hospital, Department of Pediatrics, Baylor College of Medicine, Houston, TX, United States
- Mikashmi Kohli
- FIND, Geneva, Switzerland
- Ursula Panzner
- Division of Infectious Diseases and Tropical Medicine, LMU University Hospital, Munich, Germany
- Ursula Panzner
- German Center for Infection Research (DZIF), Partner Site Munich, Munich, Germany
- Collins Musia
- German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Borstel, Germany
- Christoph Lange
- The Global Tuberculosis Program, Texas Children’s Hospital, Department of Pediatrics, Baylor College of Medicine, Houston, TX, United States
- Christoph Lange
- German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Borstel, Germany
- Christoph Lange
- Division of Clinical Infectious Diseases, Research Center Borstel, Borstel, Germany
- Christoph Lange
- 0Respiratory Medicine & International Health, University of Lübeck, Lübeck, Germany
- Anca Vasiliu
- The Global Tuberculosis Program, Texas Children’s Hospital, Department of Pediatrics, Baylor College of Medicine, Houston, TX, United States
- Anca Vasiliu
- German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Borstel, Germany
- Anca Vasiliu
- Division of Clinical Infectious Diseases, Research Center Borstel, Borstel, Germany
- Rob J. W. Arts
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
- Anna M. Mandalakas
- The Global Tuberculosis Program, Texas Children’s Hospital, Department of Pediatrics, Baylor College of Medicine, Houston, TX, United States
- Anna M. Mandalakas
- German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Borstel, Germany
- Anna M. Mandalakas
- Division of Clinical Infectious Diseases, Research Center Borstel, Borstel, Germany
- Morten Ruhwald
- FIND, Geneva, Switzerland
- Lieven J. Stuyver
- 1Janssen Global Public Health R&D, Janssen Pharmaceutica NV, Beerse, Belgium
- Reinout van Crevel
- Division of Infectious Disease and Global Health, University of St Andrews, St Andrews, United Kingdom
- Reinout van Crevel
- 2Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
- DOI
- https://doi.org/10.3389/frabi.2025.1570989
- Journal volume & issue
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Vol. 4
Abstract
Tuberculosis drug trials are primarily designed to identify antibiotic regimens with the strongest potency to kill Mycobacterium tuberculosis. 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.
Keywords
