Chapter 9 Treatment of drug-susceptible and drug-resistant tuberculosis Christoph Lange 1,2,3,4 ,Thomas Theo Brehm5,6, Dumitru Chesov 1,2,3,7 ,Yousra Kherabi8,9 and Lorenzo Guglielmetti 8,10 1 Division of Clinical Infectious Diseases, Research Center Borstel, Borstel, Germany. 2 German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Borstel, Germany. 3 Respiratory Medicine and International Health, University of Lübeck, Lübeck, Germany. 4 Baylor College of Medicine and Texas Childreńs Hospital, Global TB Program, Houston, TX, USA. 5 Division of Infectious Diseases, I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 6 German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Hamburg, Germany. 7 Nicolae Testemitanu State University of Medicine and Pharmacy, Chisinau, Republic of Moldova. 8 Sorbonne University, INSERM, U1135, Centre d’Immunologie et des Maladies Infectieuses, Cimi-Paris, Paris, France. 9 Department of Infectious Diseases, Bichat-Claude Bernard Hospital, Assistance Publique Hôpitaux de Paris, Paris, France. 10 AP-HP, Pitié-Salpêtrière Hospital, Department of Bacteriology-Hygiene, Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux, Paris, France. Corresponding author: Christoph Lange (clange@fz-borstel.de) Cite as: Lange C, Brehm TT, Chesov D, et al. Treatment of drug-susceptible and drug-resistant tuberculosis. In: García-Basteiro AL, Öner Eyüboğlu F, Rangaka MX, eds. The Challenge of Tuberculosis in the 21st Century (ERS Monograph). Sheffield, European Respiratory Society, 2023 pp. 117–138 [https://doi.org/10.1183/2312508X. 10024622]. @ERSpublications The treatment of TB has been revolutionised in recent years. This chapter presents an historical perspective and an update for the clinical management of patients with drug-susceptible and drug-resistant TB. https://bit.ly/ERSM101 Copyright ©ERS 2023. Print ISBN: 978-1-84984-169-6. Online ISBN: 978-1-84984-170-2. Print ISSN: 2312-508X. Online ISSN: 2312-5098. Recent advances have enabled the use of shorter TB treatment regimens. Key changes in the management of TB are: 1-month preventive treatment with rifapentine and isoniazid 4-month treatment for paucibacillary TB in children 4-month treatment for PTB in adults based on rifapentine and 6-month treatment for MDR/RR-TB with bedaquiline, pretomanid, linezolid and moxifloxacin (BPaLM). However, the history of TB drug resistance, and limited capacity worldwide for DST, are cause for caution. Introduction TB is a preventable and treatable infectious disease. According to the latest estimates from the WHO [1], more than 85% of patients affected by TB achieve a successful outcome with anti-TB therapies. Presently there are 21 medicines from several drug classes available for the treatment of TB [2]. Until 2022, the standard duration of anti-TB therapies was 6 months for adults and children with pulmonary disease and 18 months for those affected by RR-TB or MDR-TB [3, 4]. Recently, important achievements have been made for effective, safe and shorter treatment regimens for patients affected by drug-susceptible TB (DS-TB) and by DR-TB, which have led to revisions of WHO treatment recommendations [5–7]. With 19 compounds in clinical phase 1 https://doi.org/10.1183/2312508X.10024622 117