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DOI: 10.1055/a-2502-6525
Nichttuberkulöse Mykobakterien: diagnostische Herausforderungen und individualisierte Therapieansätze
Nontuberculous Mycobacteria: Diagnostic Challenges and Individualized Therapeutic ApproachesAuthors
Was ist neu?
Risikofaktoren für eine pulmonale NTM-Erkrankung
Bronchiektasen sind mit dem höchsten Risiko für NTM-PD assoziiert (OR 21,5). Weitere Risikofaktoren: frühere Tuberkulose, interstitielle Lungenerkrankungen, chronisch obstruktive Lungenerkrankung (COPD), Asthma, zystische Fibrose (CF), variables Immundefekt-Syndrom (CVID), α1-Antitrypsin-Mangel. Systemische Immunsuppression und inhalative Kortikosteroide gelten als relevante Risikofaktoren. Bestimmte Patient*innen mit NTM-PD zeigen charakteristische Merkmale wie eine schlanke Statur, Pectus excavatum und CFTR-Mutationen.
Definition der pulmonalen nichttuberkulösen Mykobakteriose
NTM-PD ist durch 3 Kriterien definiert: klinische Symptome, radiologische Veränderungen und den mikrobiologischen Erregernachweis. Häufigste Erreger: Mycobacterium-avium-Komplex (MAC), Mycobacterium kansasii und Mycobacterium abscessus.
Diagnostik
Der serologische anti-GPL-IgA-Test ermöglicht die Unterscheidung zwischen Kolonisation und Erkrankung. Ein neuer, serumbasierter CRISPR-Cas-Test auf MAC-cfDNA zeigt >90% Sensitivität und >97% Spezifität. Die Konzentration zirkulierender cfDNA korreliert mit dem Therapie-Ansprechen. Die klassische Sputumkultur bleibt essenziell für eine Speziesdiagnostik und Resistenztestung.
Therapie
Die Standardtherapie von NTM besteht in der Regel aus einer langdauernden Kombinationstherapie mit einem Makrolid und weiteren Antibiotika, angepasst an Spezies und Resistenzlage. ALIS (inhalatives liposomales Amikacin) zeigte in der ARISE-Studie eine signifikant höhere Kulturkonversion bei refraktärer MAC-Erkrankung. Rifampicin wird bei MAC wegen der unzureichenden Wirkspiegel kritisch hinterfragt. Mycobacterium abscessus bleibt therapeutisch besonders herausfordernd. Therapiepläne erfordern eine spezies- und resistenzbasierte Auswahl der Antibiotika-Kombination. Die Verträglichkeit der Langzeit-Therapie ist limitiert und eine engmaschige klinische Überwachung ist erforderlich. Mycobacterium xenopi ist prognostisch ungünstiger; hier lautet die Therapie-Empfehlung: mindestens 3 Substanzen plus ggf. parenterales Amikacin.
Abstract
Non-tuberculous mycobacteria (NTM) are increasingly recognized as clinically relevant pathogens, particularly in countries with a low tuberculosis incidence. Recent data from Denmark demonstrate a continuous annual rise in NTM-related pulmonary disease (NTM-PD) of 4.6% over 3 decades, with more than half of the isolates associated with true disease. Structural lung diseases such as bronchiectasis, prior tuberculosis, and chronic pulmonary conditions are major risk factors, alongside immunodeficiencies and immunosuppressive therapies. The diagnosis of NTM-PD requires a combination of clinical symptoms, radiological findings, and the microbiological confirmation. Novel diagnostic tools, such as anti-GPL IgA serology and a CRISPR-Cas-based cfDNA assay, show promise for differentiating colonization from disease and monitoring treatment response, but the sputum culture remains essential for species identification and drug susceptibility testing. Treatment is complex and species-specific, with macrolides forming the backbone of most regimens. Refractory cases, particularly those involving Mycobacterium abscessus, pose therapeutic challenges and often require multidisciplinary management. Inhaled liposomal amikacin (ALIS) has shown benefit in refractory MAC disease. Clinical decision-making must balance efficacy, tolerability, and long-term adherence, highlighting the need for individualized treatment strategies and regular monitoring. This review outlines current evidence and practical recommendations for clinicians managing NTM-PD.
Publication History
Article published online:
28 October 2025
© 2025. Thieme. All rights reserved.
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Literatur
- 1 Ratnatunga CN, Lutzky VP, Kupz A. et al. The Rise of Non-Tuberculosis Mycobacterial Lung Disease. Front Immunol 2020; 11: 303
- 2 Jarchow-MacDonald A, Smith M, Seagar AL. et al. Changing Incidence and Characteristics of Nontuberculous Mycobacterial Infections in Scotland and Comparison With Mycobacterium tuberculosis Complex Incidence (2011 to 2019). Open Forum Infect Dis 2023; 10 (01) ofac665
- 3 Dahl VN, Pedersen AA, Norman A. et al. Clinical Significance, Species Distribution, and Temporal Trends of Nontuberculous Mycobacteria, Denmark, 1991–2022. Emerg Infect Dis 2024; 30 (09) 1755-1762
- 4 Hermansen TS, Ravn P, Svensson E. et al. Nontuberculous mycobacteria in Denmark, incidence and clinical importance during the last quarter-century. Sci Rep 2017; 7 (01) 6696
- 5 Andréjak C, Thomsen VØ, Johansen IS. et al. Nontuberculous pulmonary mycobacteriosis in Denmark: incidence and prognostic factors. Am J Respir Crit Care Med 2010; 181 (05) 514-521
- 6 Wetzstein N, Dahl VN, Lillebaek T. et al. Clinical spectrum and relevance of Mycobacterium malmoense: Systematic review and meta-analysis of 859 patients. J Infect 2024; 89 (02) 106203
- 7 Loebinger MR, Aliberti S, Haworth C. et al. Patients at risk of nontuberculous mycobacterial pulmonary disease who need testing evaluated using a modified Delphi process by European experts. ERJ Open Res 2024; 10 (05) 00791-2023
- 8 Nguyen MVH, Haas MK, Kasperbauer SH. et al. Nontuberculous Mycobacterial Pulmonary Disease: Patients, Principles, and Prospects. Clin Infect Dis Off Publ Infect Dis Soc Am 2024; 79 (04) e27-47
- 9 Loebinger MR, Quint JK, van der Laan R. et al. Risk Factors for Nontuberculous Mycobacterial Pulmonary Disease: A Systematic Literature Review and Meta-Analysis. Chest 2023; 164 (05) 1115-1124
- 10 Daley CL, Iaccarino JM, Lange C. et al. Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA clinical practice guideline. Eur Respir J 2020; 56 (01) 2000535
- 11 Dettmer S, Ringshausen FC, Fuge J. et al. Computed Tomography in Adults with Bronchiectasis and Nontuberculous Mycobacterial Pulmonary Disease: Typical Imaging Findings. J Clin Med 2021; 10 (12) 2736
- 12 Choi H, Hughes C, Eke Z. et al. Clinical Efficacy of Serum Antiglycopeptidolipid Core IgA Antibody Test for Screening Nontuberculous Mycobacterial Pulmonary Disease in Bronchiectasis. Chest 2025; 167 (05) 1300-1310
- 13 Kitada S, Yoshimura K, Miki K. et al. Validation of a commercial serodiagnostic kit for diagnosing pulmonary Mycobacterium avium complex disease. Int J Tuberc Lung Dis Off J Int Union Tuberc Lung Dis 2015; 19 (01) 97-103
- 14 Li L, Henkle E, Youngquist BM. et al. Serum Cell-Free DNA-based Detection of Mycobacterium avium Complex Infection. Am J Respir Crit Care Med 2024; 209 (10) 1246-1254
- 15 Ringshausen FC, Baumann I, de Roux A. et al. Management of adult bronchiectasis – Consensus-based Guidelines for the German Respiratory Society (DGP) e. V. (AWMF Registernummer 020–030). Pneumol 2024; 78 (11) 833-899
- 16 Dartois V, Dick T. Toward better cures for Mycobacterium abscessus lung disease. Clin Microbiol Rev 2024; 37: e00080-23
- 17 Daley CL, Chalmers JD, Flume PA. et al. Trial Conduct, Baseline Characteristics, and Symptom Burden of Patients in the ARISE Study. Pulm Ther 2025; 11 (02) 269-283
- 18 Andréjak C, Lescure FX, Pukenyte E. et al. Mycobacterium xenopi pulmonary infections: a multicentric retrospective study of 136 cases in north-east France. Thorax 2009; 64 (04) 291-296
- 19 Dettmer S, Heiß-Neumann M, Wege S. et al. Evaluation of treatment response with serial CT in patients with non-tuberculous mycobacterial pulmonary disease. Eur Radiol 2025; 35 (02) 798-805
- 20 Andréjak C, Nielsen R, Thomsen VØ. et al. Chronic respiratory disease, inhaled corticosteroids and risk of non-tuberculous mycobacteriosis. Thorax 2013; 68 (03) 256-262
