Therapeutic developments for tuberculosis and nontuberculous mycobacterial lung disease - Nature.com
Abstract
Tuberculosis (TB) drug discovery and development has undergone nothing short of a revolution over the past 20 years. Successful public–private partnerships and sustained funding have delivered a much-improved understanding of mycobacterial disease biology and pharmacology and a healthy pipeline that can tolerate inevitable attrition. Preclinical and clinical development has evolved from decade-old concepts to adaptive designs that permit rapid evaluation of regimens that might greatly shorten treatment duration over the next decade. But the past 20 years also saw the rise of a fatal and difficult-to-cure lung disease caused by nontuberculous mycobacteria (NTM), for which the drug development pipeline is nearly empty. Here, we discuss the similarities and differences between TB and NTM lung diseases, compare the preclinical and clinical advances, and identify major knowledge gaps and areas of cross-fertilization. We argue that applying paradigms and networks that have proved successful for TB, from basic research to clinical trials, will help to populate the pipeline and accelerate curative regimen development for NTM disease.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Anti-tuberculosis treatment strategies and drug development: challenges and priorities
Moving tuberculosis vaccines from theory to practice
A multi-scale pipeline linking drug transcriptomics with pharmacokinetics predicts in vivo interactions of tuberculosis drugs
References
WHO. Global Tuberculosis Report https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2022 (Geneva, 2022).
Pai, M., Kasaeva, T. & Swaminathan, S. Covid-19's devastating effect on tuberculosis care – a path to recovery. N. Engl. J. Med. 386, 1490–1493 (2022).
Marais, B. J., Hesseling, A. C. & Cotton, M. F. Poverty and tuberculosis: is it truly a simple inverse linear correlation? Eur. Respir. J. 33, 943–944 (2009).
Dartois, V. A. & Rubin, E. J. Anti-tuberculosis treatment strategies and drug development: challenges and priorities. Nat. Rev. Microbiol. 20, 685–701 (2022).
WHO. Global Tuberculosis Report https://www.who.int/publications/i/item/9789240037021 (Geneva, 2021).
WHO. WHO Consolidated Guidelines on Tuberculosis. Module 4: Drug-resistant Tuberculosis Treatment https://www.who.int/publications/i/item/9789240007048 (Geneva, 2020).
Motta, I. et al. Recent advances in the treatment of tuberculosis. Clin. Microbiol. Infect. https://doi.org/10.1016/j.cmi.2023.07.013 (2023).
Evangelopoulos, D. & McHugh, T. D. Improving the tuberculosis drug development pipeline. Chem. Biol. Drug Des. 86, 951–960 (2015).
Cowman, S., van Ingen, J., Griffith, D. E. & Loebinger, M. R. Non-tuberculous mycobacterial pulmonary disease. Eur. Respir. J. 54, 1900250 (2019).
Winthrop, K. L. et al. Incidence and prevalence of nontuberculous mycobacterial lung disease in a large U.S. managed care health plan, 2008–2015. Ann. Am. Thorac. Soc. 17, 178–185 (2020).
Prevots, D. R. & Marras, T. K. Epidemiology of human pulmonary infection with nontuberculous mycobacteria: a review. Clin. Chest Med. 36, 13–34 (2015).
Raju, R. M., Raju, S. M., Zhao, Y. & Rubin, E. J. Leveraging advances in tuberculosis diagnosis and treatment to address nontuberculous mycobacterial disease. Emerg. Infect. Dis. 22, 365–369 (2016).
Sawka, A. & Burke, A. Medications and monitoring in treatment of nontuberculous mycobacteria lung disease. Clin. Chest Med. 44, 815–828 (2023).
Daley, C. L. et al. Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA clinical practice guideline. Clin. Infect. Dis. 71, 905–913 (2020). A comprehensive review by US and European physicians of evidence-based recommendations for the treatment of NTM-PD.
Egorova, A., Jackson, M., Gavrilyuk, V. & Makarov, V. Pipeline of anti-Mycobacterium abscessus small molecules: repurposable drugs and promising novel chemical entities. Med. Res. Rev. 41, 2350–2387 (2021). A comprehensive review of the clinical and preclinical pipeline for MAB-PD, by mechanism of action and target.
Johansen, M. D., Herrmann, J. L. & Kremer, L. Non-tuberculous mycobacteria and the rise of Mycobacterium abscessus. Nat. Rev. Microbiol. 18, 392–407 (2020). A review covering the biology, virulence factors, host interactions and drug resistance mechanisms of M. abscessus, one of the most antibiotic-resistant mycobacteria.
Griffith, D. E. & Aksamit, T. R. Understanding nontuberculous mycobacterial lung disease: it's been a long time coming. F1000Res 5, 2797 (2016).
Young, C., Walzl, G. & Du Plessis, N. Therapeutic host-directed strategies to improve outcome in tuberculosis. Mucosal Immunol. 13, 190–204 (2020).
Tiwari, D. & Martineau, A. R. Inflammation-mediated tissue damage in pulmonary tuberculosis and host-directed therapeutic strategies. Semin. Immunol. 65, 101672 (2022).
Lee, A., Xie, Y. L., Barry, C. E. & Chen, R. Y. Current and future treatments for tuberculosis. BMJ 368, m216 (2020).
Anidi, I. U. & Olivier, K. N. Host-directed therapy in nontuberculous mycobacterial pulmonary disease: preclinical and clinical data review. Clin. Chest Med. 44, 839–845 (2023).
Hatfull, G. F. Phage therapy for nontuberculous mycobacteria: challenges and opportunities. Pulm. Ther. 9, 91–107 (2022).
Sterling, T. R. et al. Guidelines for the treatment of latent tuberculosis infection: recommendations from the National Tuberculosis Controllers Association and CDC, 2020. MMWR Recomm. Rep. 69, 1–11 (2020).
Kumar, K. & Loebinger, M. R. Nontuberculous mycobacterial pulmonary disease: clinical epidemiologic features, risk factors, and diagnosis: the nontuberculous mycobacterial series. Chest 161, 637–646 (2022).
Sharma, S. K., Mohan, A. & Kohli, M. Extrapulmonary tuberculosis. Expert. Rev. Respir. Med. 15, 931–948 (2021).
Shih, D. C. et al. Extrapulmonary nontuberculous mycobacterial disease surveillance – Oregon, 2014–2016. MMWR Morb. Mortal. Wkly Rep. 67, 854–857 (2018).
Wilkinson, R. J. et al. Tuberculous meningitis. Nat. Rev. Neurol. 13, 581–598 (2017).
Ganchua, S. K. C., White, A. G., Klein, E. C. & Flynn, J. L. Lymph nodes — the neglected battlefield in tuberculosis. PLoS Pathog. 16, e1008632 (2020).
Lin, P. L. et al. Sterilization of granulomas is common in active and latent tuberculosis despite within-host variability in bacterial killing. Nat. Med. 20, 75–79 (2014).
Xie, Y. L. et al. Fourteen-day PET/CT imaging to monitor drug combination activity in treated individuals with tuberculosis. Sci. Transl. Med. 13, eabd7618 (2021).
Zhu, J., Liu, Y. J. & Fortune, S. M. Spatiotemporal perspectives on tuberculosis chemotherapy. Curr. Opin. Microbiol. 72, 102266 (2023).
Dorman, S. E. et al. Four-month rifapentine regimens with or without moxifloxacin for tuberculosis. N. Engl. J. Med. 384, 1705–1718 (2021). The first successful trial in more than four decades of treatment shortening in patients with DS-TB, reducing therapy duration from 6 to 4 months.
Conradie, F. et al. Treatment of highly drug-resistant pulmonary tuberculosis. N. Engl. J. Med. 382, 893–902 (2020). A landmark clinical trial that successfully reduced treatment duration from 18–24 months to 6 months for patients with drug-resistant TB, showing the power of novel mechanisms of action.
Dahl, V. N. et al. Global trends of pulmonary infections with nontuberculous mycobacteria: a systematic review. Int. J. Infect. Dis. 125, 120–131 (2022).
Honda, J. R., Bernhard, J. N. & Chan, E. D. Natural disasters and nontuberculous mycobacteria: a recipe for increased disease? Chest 147, 304–308 (2015).
Mirsaeidi, M. & Sadikot, R. T. Gender susceptibility to mycobacterial infections in patients with non-CF bronchiectasis. Int. J. Mycobacteriol. 4, 92–96 (2015).
Andrejak, C. et al. Chronic respiratory disease, inhaled corticosteroids and risk of non-tuberculous mycobacteriosis. Thorax 68, 256–262 (2013).
Chan, E. D. & Iseman, M. D. Underlying host risk factors for nontuberculous mycobacterial lung disease. Semin. Respir. Crit. Care Med. 34, 110–123 (2013).
Abidin, N. Z. et al. Trends in nontuberculous mycobacteria infection in children and young people with cystic fibrosis. J. Cyst. Fibros. 20, 737–741 (2021).
Brugha, R. & Spencer, H. Mycobacterium abscessus in cystic fibrosis. Science 372, 465–466 (2021).
Honda, J. R., Virdi, R. & Chan, E. D. Global environmental nontuberculous mycobacteria and their contemporaneous man-made and natural niches. Front. Microbiol. 9, 2029 (2018).
Kim, D. H. et al. In vitro activity and clinical outcomes of clofazimine for nontuberculous mycobacteria pulmonary disease. J. Clin. Med. 10, 4581 (2021).
Pfaeffle, H. O. I. et al. Clofazimine for treatment of multidrug-resistant non-tuberculous mycobacteria. Pulm. Pharmacol. Ther. 70, 102058 (2021).
Holt, M. R. & Baird, T. Treatment approaches to Mycobacterium abscessus pulmonary disease. Clin. Chest Med....
Comments
Post a Comment