Therapie bei MDR-, prä-XDR-, XDR-Tuberkulose und Rifampicin-Resistenz oder bei Medikamentenunverträglichkeit gegenüber mindestens Rifampicin^[*]

Zusammenfassung

Im Dezember 2022 hat die Weltgesundheitsorganisation (WHO) die Empfehlungen für die Behandlung der medikamentenresistenten Tuberkulose (TB) aktualisiert. Die Bewertung dieser Empfehlungen und der neuen Studiendaten macht auch für den deutschsprachigen Raum eine Aktualisierung der Leitlinienempfehlungen zur Therapie der mindestens Rifampicin-resistenten Tuberkulose notwendig, welche die entsprechenden Kapitel ersetzt. Auch für Deutschland, Österreich und die Schweiz wird nun eine verkürzte, mindestens 6-monatige MDR-TB-Therapie unter Einsatz der festgelegten und nicht veränderbaren Medikamentenkombination Bedaquilin, Pretomanid, Linezolid und Moxifloxacin (BPaLM) empfohlen, wenn alle hierfür notwendigen Voraussetzungen erfüllt sind. Diese Empfehlung gilt für TB-Fälle mit nachgewiesener Rifampicin-Resistenz einschließlich der Rifampicin-Monoresistenz. Zur Behandlung der präextensiven (prä-XDR) TB wird weiterhin in erster Linie eine individualisierte, an die Resistenzdaten angepasste Therapie über 18 Monate empfohlen. Die nicht veränderbare Medikamentenkombination Bedaquilin, Pretomanid und Linezolid (BPaL) kann bei prä-XDR alternativ angewendet werden, wenn alle Voraussetzungen dafür erfüllt sind. Die notwendigen Voraussetzungen für den Einsatz von BPaLM und BPaL werden in diesem Amendment zur S2k-Leitlinie „Tuberkulose im Erwachsenenalter“ begründet dargestellt.

Abstract

In December 2022, based on the assessment of new evidence, the World Health Organization (WHO) updated its guidelines for the treatment of drug-resistant tuberculosis (TB). The evaluation of both, these recommendations, and the latest study data, makes it necessary to update the existing guidelines on the treatment of at least rifampicin-resistant tuberculosis for the German-speaking region, hereby replacing the respective chapters. A shortened MDR-TB treatment of at least 6 month using the fixed and non-modifiable drug combination of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) is now also recommended for Germany, Austria, and Switzerland under certain conditions. This recommendation applies to TB cases with proven rifampicin resistance, including rifampicin monoresistance. For treatment of pre-extensively drug resistant TB (pre-XDR-TB), an individualized treatment for 18 months adjusted to resistance data continues to be the primary recommendation. The non-modifiable drug combination of bedaquiline, pretomanid, and linezolid (BPaL) may be used alternatively in pre-XDR TB if all prerequisites are met. The necessary prerequisites for the use of BPaLM and BPaL are presented in this amendment to the S2k guideline for ‘Tuberculosis in adulthood’.

^* Version: Erstveröffentlichung der S2k-Leitlinie 2017, Update 2022, aktuelles Amendment 2023

Publication History

Article published online:
06 November 2023

• 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 DOI: 10.1055/s-0043-105954.
• 2 World Health Organization. WHO consolidated guidelines on tuberculosis. Module 4: treatment – drug-resistant tuberculosis treatment, 2022 update.Licence: CC BY-NC-SA 3.0 IGO. Geneva: World Health Organization; 2022
• 3 Conradie F, Bagdasaryan TR, Borisov S. et al. Bedaquiline-Pretomanid-Linezolid Regimens for Drug-Resistant Tuberculosis. N Engl J Med 2022; 387: 810-823 DOI: 10.1056/NEJMoa2119430.
• 4 Conradie F, Diacon AH, Ngubane N. et al. Treatment of Highly Drug-Resistant Pulmonary Tuberculosis. N Engl J Med 2020; 382: 893-902 DOI: 10.1056/NEJMoa1901814.
• 5 Nyang'wa BT, Berry C, Kazounis E. et al. A 24-Week, All-Oral Regimen for Rifampin-Resistant Tuberculosis. N Engl J Med 2022; 387: 2331-2343 DOI: 10.1056/NEJMoa2117166.
• 6 Brodhun B, Altmann D, Hauer B. et al. Bericht zur Epidemiologie der Tuberkulose in Deutschland für 2021. Robert Koch-Institut; 2022. DOI: 10.25646/10144
• 7 World Health Organisation. Active tuberculosis drug-safety monitoring and management (aDSM) – Framework for implementation. Geneva: World Health Organisation; 2015
• 8 Ahmad N, Ahuja SD, Akkerman OW. et al. Treatment correlates of successful outcomes in pulmonary multidrug-resistant tuberculosis: an individual patient data meta-analysis. Lancet 2018; 392: 821-834 DOI: 10.1016/S0140-6736(18)3164.
• 9 Grobbel HP, Merker M, Köhler N. et al. Design of multidrug-resistant tuberculosis treatment regimens based on DNA sequencing. Clin Infect Dis 2021; 73: 1194-1202 DOI: 10.1093/cid/ciab359.
• 10 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 DOI: 10.1183/13993003.03492-2020.
• 11 World Health Organization. WHO consolidated guidelines on tuberculosis. Module 4: treatment – drug-resistant tuberculosis treatment. Licence: CC BY-NC-SA 3.0 IGO. Geneva: World Health Organization; 2020
• 12 World Health Organization. WHO consolidated guidelines on drug-resistant tuberculosis treatment. Licence: CC BY-NC-SA 3.0 IGO. Geneva: World Health Organization; 2019
• 13 World Health Organization. Catalogue of mutations in Mycobacterium tuberculosis complex and their association with drug resistance. Licence: CC BY-NC-SA 3.0 IGO. Geneva: World Health Organization; 2021
• 14 Mirzayev F, Viney K, Linh NN. et al. World Health Organization recommendations on the treatment of drug-resistant tuberculosis, 2020 update. Eur Respir J 2020; 57: 2003300 DOI: 10.1183/13993003.03300-2020.
• 15 Otto-Knapp R, Bös L, Schönfeld N. et al. Resistenzen gegen Zweitlinienmedikamente bei Migranten mit multiresistenter Tuberkulose in der Region Berlin. Pneumologie 2014; 68: 496-500 DOI: 10.1055/s-0034-1377226.
• 16 Glasauer S, Altmann D, Hauer B. et al. First-line tuberculosis drug resistance patterns and associated risk factors in Germany, 2008–2017. PLoS One 2019; 14: e0217597 DOI: 10.1371/journal.pone.0217597.
• 17 Lange C, Duarte R, Fréchet-Jachym M. et al. Limited Benefit of the New Shorter Multidrug-Resistant Tuberculosis Regimen in Europe. Am J Respir Crit Care Med 2016; 194: 1029-103 DOI: 10.1164/rccm.201606-1097LE.
• 18 Günther G, van Leth F, Alexandru S. et al. Multidrug-resistant tuberculosis in Europe, 2010–2011. Emerg Infect Dis 2015; 21: 409-416 DOI: 10.3201/eid2103.141343.
• 19 Wen S, Jing W, Zhang T. et al. Comparison of in vitro activity of the nitroimidazoles delamanid and pretomanid against multidrug-resistant and extensively drug-resistant tuberculosis. Eur J Clin Microbiol Infect Dis 2019; 38: 1293-1296 DOI: 10.1007/s10096-019-03551-w.
• 20 Rifat D, Li SY, Ioerger T. et al. Mutations in fbiD (Rv2983) as a Novel Determinant of Resistance to Pretomanid and Delamanid in Mycobacterium tuberculosis. Antimicrob Agents Chemother 2020; 65 DOI: 10.1128/AAC.01948-20.
• 21 Mudde SE, Upton AM, Lenaerts A. et al. Delamanid or pretomanid? A Solomonic judgement!. J Antimicrob Chemother 2022; 77: 880-902 DOI: 10.1093/jac/dkab505.
• 22 European Medicines Agency. Dovprela (previously Pretomanid FGK). EPAR – Product Information, first published 11/08/2020. Updated 13/06/2023.
• 23 Imperial MZ, Nedelman JR, Conradie F. et al. Proposed Linezolid Dosing Strategies to Minimize Adverse Events for Treatment of Extensively Drug-Resistant Tuberculosis. Clin Infect Dis 2022; 74: 1736-1747 DOI: 10.1093/cid/ciab699.
• 24 Padmapriyadarsini C, Solanki R, Jeyakumar SM. et al. Linezolid Pharmacokinetics and Its Association with Adverse Drug Reactions in Patients with Drug-Resistant Pulmonary Tuberculosis. Antibiotics (Basel) 2023; 12 DOI: 10.3390/antibiotics12040714.