Update: Therapie der medikamentenresistenten Tuberkulose (DR-TB) in Deutschland, Österreich und der Schweiz

Zusammenfassung

In der Folge neuer Empfehlungen der Weltgesundheitsorganisation (WHO) zur Therapie der Tuberkulose (TB) im Jahr 2025 hat sich die Tuberkulose-Leitliniengruppe für Deutschland, Österreich und die Schweiz entschlossen, die Leitlinien für die Therapie der medikamentenresistenten Tuberkulose (engl. drug-resistant tuberculosis; DR-TB) zu aktualisieren.

DR-TB umfasst resistente Formen von Mycobacterium tuberculosis, darunter Isoniazid-Monoresistenz, multiresistente/Rifampicin-resistente TB (MDR/RR-TB), präextensiv resistente TB (prä-XDR-TB) und extensiv resistente TB (XDR-TB). Für MDR/RR-TB und prä-XDR-TB ohne zusätzliche Resistenz gegen Bedaquilin oder Linezolid werden bevorzugt zwei 6-monatige, rein orale Kurzzeitregime empfohlen (BPaLM* oder BDLLfx* bei MDR/RR-TB und BPaL* oder BDLC* bei prä-XDR-TB [*B = Bedaquilin, C = Clofazimin, D = Delamanid, L = Linezolid, Lfx = Levofloxacin, M = Moxifloxacin, Pa = Pretomanid]). Bei schwerer oder ausgedehnter Erkrankung sowie Immunsuppression sollte die Therapie auf z. B. 9 Monate verlängert oder als individualisiertes 18-Monats-Regime durchgeführt werden. Für XDR-TB sowie Unverträglichkeiten gegenüber Bedaquilin oder Linezolid gelten individualisierte Kombinationstherapien mit mindestens 4 wirksamen Substanzen über mindestens 18 Monate. Neben pharmakologischen Aspekten betont diese Aktualisierung die Bedeutung qualitätsgesicherter Diagnostik, gesicherter Medikamentenversorgung und sozialmedizinischer Begleitung zur Vermeidung von Therapieabbrüchen. Aufgrund der geringen Fallzahlen wird eine Behandlung in spezialisierten Zentren oder in Kooperation mit diesen empfohlen. Ziel ist eine wirksame, verträgliche und an die Resistenzlage angepasste Behandlung, um den Therapieerfolg zu sichern und eine weitere Resistenzentwicklung zu verhindern.

Abstract

Following new recommendations from the World Health Organization (WHO) on the treatment of tuberculosis (TB) in 2025, the Tuberculosis Guidelines Group for Germany, Austria and Switzerland has decided to update the guidelines for the treatment of drug-resistant tuberculosis (DR-TB) as well. DR-TB includes resistant forms of Mycobacterium tuberculosis, including isoniazid monoresistance, multidrug-resistant/rifampicin-resistant TB (MDR/RR-TB), pre-extensively drug-resistant TB (pre-XDR-TB) and extensively drug-resistant TB (XDR-TB). For MDR/RR-TB and pre-XDR-TB without additional resistance to bedaquiline and/or linezolid, two 6-month, purely oral short-term regimens are recommended (BPaLM or BDLLfx for MDR/RR-TB and BPaL or BDLC for pre-XDR-TB [*B = bedaquiline, C = clofazimine, D = delamanid, L = linezolid, Lfx = levofloxacin; M = moxifloxacin; Pa = pretomanid]). In cases of severe or extensive disease and immunosuppression, therapy can be extended to 9 months, for example, or carried out as an individualized 18-month regimen. For XDR-TB and intolerance to bedaquiline or linezolid, individualized combination therapies with at least four effective substances are recommended. In addition to pharmacological aspects, this update emphasizes the importance of quality-assured diagnostics, secure drug supply and socio-medical support to prevent treatment discontinuation. Due to the low number of cases, treatment in specialized centers or in cooperation with them is recommended. The aim is to provide effective, tolerable therapy that is adapted to the resistance situation in order to ensure therapeutic success and prevent further development of drug-resistance.

Publication History

Article published online:
03 November 2025

• Literatur

• 1 Schaberg T, Brinkmann F, Feiterna-Sperling C. et al. [Tuberculosis in adulthood – The Sk2-Guideline of the German Central Committee against Tuberculosis (DZK) and the German Respiratory Society (DGP) for the diagnosis and treatment of adult tuberculosis patients]. Pneumologie 2022; 76: 727-819
• 2 Dheda K, Mirzayev F, Cirillo DM. et al. Multidrug-resistant tuberculosis. Nat Rev Dis Primers 2024; 10: 22
• 3 Robert-Koch-Institut. Bericht zur Epidemiologie der Tuberkulose in Deutschland für 2023. 2025
• 4 Vasiliu A, Cristea V, Stoycheva K. et al. Shifting tuberculosis dynamics in the EU/EEA: geographical and drug resistance trends among people of foreign origin, 2019 to 2023. Euro Surveill 2025; 30: 2500173
• 5 Friesen I. Welttuberkulosetag 2025 – Yes! We Can End TB: Commit, Invest, Deliver. Epid Bull 2025; 12: 3-6
• 6 World Health Organization. Global tuberculosis report 2024. Geneva Switzerland: 2024
• 7 Gunther G, van Leth F, Alexandru S. et al. Multidrug-resistant tuberculosis in Europe, 2010-2011. Emerg Infect Dis 2015; 21: 409-416
• 8 Kunst H, Lange B, Hovardovska O. et al. Tuberculosis in adult migrants in Europe: a TBnet consensus statement. Eur Respir J 2025; 65: 2401612
• 9 World Health Organization. WHO consolidated guidelines on tuberculosis. Module 4: treatment and care. Geneva, Switzerland: 2025
• 10 World Health Organization. WHO consolidated operational handbook on tuberculosis. Module 4: treatment and care. Geneva, Switzerland: 2025
• 11 Otto-Knapp R, Bauer T, Brinkmann F. et al. [Treatment of MDR, pre-XDR, XDR and rifampicin resistant tuberculosis or in case of intolerance to at least rifampicin in Austria, Germany and Switzerland – Amendment dated 19.09.2023 to the Sk2-Guideline: Tuberculosis in adulthood of the German Central Committee against Tuberculosis (DZK) on behalf of the German Respiratory Society (DGP)]. Pneumologie 2024; 78: 35-46
• 12 Maier C, Chesov D, Schaub D. et al. Long-term treatment outcomes in patients with multidrug-resistant tuberculosis. Clin Microbiol Infect 2023; 29: 751-757
• 13 Hughes JA, Solans BP, Garcia-Prats AJ. et al. Pharmacokinetics and Safety of Clofazimine in Children With Rifampicin-Resistant Tuberculosis. J Infect Dis 2025; 231: e873-e881
• 14 Guglielmetti L, Khan U, Velasquez GE. et al. Bedaquiline, delamanid, linezolid, and clofazimine for rifampicin-resistant and fluoroquinolone-resistant tuberculosis (endTB-Q): an open-label, multicentre, stratified, non-inferiority, randomised, controlled, phase 3 trial. Lancet Respir Med 2025; 13: P809-P820
• 15 Kuksa L, Andrejak C, Haecker B. et al. Urgent request for pretomanid label expansion to align with WHO guidelines and improve treatment accessibility and efficacy. IJTLD Open 2025; 2: 117-119
• 16 Chang VK, Imperial MZ, Phillips PPJ. et al. Risk-stratified treatment for drug-susceptible pulmonary tuberculosis. Nat Commun 2024; 15: 9400
• 17 Imperial MZ, Phillips PPJ, Nahid P. et al. Precision-Enhancing Risk Stratification Tools for Selecting Optimal Treatment Durations in Tuberculosis Clinical Trials. Am J Respir Crit Care Med 2021; 204: 1086-1096
• 18 Campbell JR, Brode SK, Barry P. et al. Association of indicators of extensive disease and rifampin-resistant tuberculosis treatment outcomes: an individual participant data meta-analysis. Thorax 2024; 79: 169-178
• 19 Heyckendorf J, Marwitz S, Reimann M. et al. Prediction of anti-tuberculosis treatment duration based on a 22-gene transcriptomic model. Eur Respir J 2021; 58: 2003492
• 20 Otto-Knapp R, Hacker B, Krieger D. et al. Long-term multidrug- and rifampicin-resistant tuberculosis treatment outcome by new WHO definitions in Germany. Eur Respir J 2022; 60: 2200765
• 21 Nardell EA. Transmission and Institutional Infection Control of Tuberculosis. Cold Spring Harb Perspect Med 2015; 6: a018192
• 22 Donald PR, Diacon AH, Lange C. et al. Droplets, dust and guinea pigs: an historical review of tuberculosis transmission research, 1878–1940. Int J Tuberc Lung Dis 2018; 22: 972-982
• 23 Witte P, Arvand M, Barth S. et al. [Tuberculosis Infection Control & Hygiene – Recommendations of the DZK]. Pneumologie 2023; 77: 983-1000