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Infektionen mit nichttuberkulösen Mykobakterien bei Patienten mit Immundefekten

Infections with nontuberculous mycobacteria in patients with immune deficiencies

Der Pneumologe volume 8, pages 412–417 (2011)Cite this article

Zusammenfassung

Infektionen mit nichttuberkulösen Mykobakterien (NTM) präsentieren sich unter dem Bild isolierter pulmonaler Infektionen, einer Lymphadenitis, Läsionen der Haut und der Weichteile oder aber als disseminierte Infektion. Bei Patienten mit angeborenen oder erworbenen Immundefekten kommen sowohl disseminierte als auch lokalisierte Infektionen häufiger vor als bei immunkompetenten Patienten. Eine Zuordnung des NTM-Nachweises in Patientenmaterialien zu einem bestimmten Krankheitsbild ist häufig schwierig, da sowohl eine Kontamination, eine Besiedlung oder eine Infektion hierfür infrage kommen kann. Aus diesem Grund ist eine genaue Kenntnis zugrunde liegender Immundefekte des Patienten neben den klinischen Kriterien wichtig für die Diagnose einer NTM-Infektion. Insbesondere die Zunahme aggressiver immunsuppressiver Therapiestrategien mit Biologicals bei chronisch-entzündlichen Systemerkrankungen hat zu einer Zunahme lokaler und invasiver NTM-Infektionen geführt. Finden sich bei pulmonalen Infektionen zumeist Mykobakterien des M.-avium-Komplexes (MAC) oder M. kansasii, so bereiten bei Haut- und Weichteilinfektionen insbesondere die schnell wachsenden M. fortuitum und M. chelonae Probleme. Therapeutisch von Bedeutung ist die Kenntnis eines zugrunde liegenden Immundefektes aufgrund einer verlängerten Therapiedauer bei Vorliegen einer disseminierten NTM-Infektion. Eine relativ neue Erkenntnis sind die Reaktivierungen von Mykobakteriosen im Rahmen von Immunrekonstitutions- und Inflammationssyndomen (IRIS) unter antiretroviraler Therapie bei HIV/Aids-Patienten.

Abstract

Infections caused by nontuberculous mycobacteria (NTM) cause a variety of clinical pictures, like nodular or cavitary lung infiltrations, lymphadenitis or lesions of the skin and soft tissue. In patients with innate or acquired immune deficiencies, an increase of disseminated but also local, atypical disease manifestations is observed. Detailed knowledge about underlying immune defects and the current immune status of patients with suspected NTM infections is indispensable to verify the detection of NTM in clinical specimens which does not necessarily account for a direct disease association. Differences in the growth kinetics of bacteria from the M. avium complex (MAC) which primarily cause lung diseases in contrast to the rapidly growing M. fortuitum and M. chelonae (RGM) involved in skin and soft tissue infections have to be considered in the diagnostics of NTM infections. Emergence of treatment strategies including biologicals in chronic inflammatory diseases resulted in an increase of local and disseminated NTM infections in the past. The duration of NTM treatment may be prolonged in patients with underlying immune deficiencies and disseminated infections. NTM prophylaxis should be discussed in HIV/AIDS patients with severe immune deficiency (CD4  < 50/µl) starting with antiretroviral therapy (cART) as NTM infections presenting as lymphadenitis are frequently observed in patients with immune reconstitution inflammatory syndrome (IRIS).

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Literatur

  1. Cassidy PM, Hedberg K, Saulson A et al (2009) Nontuberculous mycobacterial disease prevalence and risk factors: a changing epidemiology. Clin Infect Dis 49:e124–e129

    PubMed  Article  Google Scholar 

  2. Horsburgh CR Jr (1996) Epidemiology of disease caused by nontuberculous mycobacteria. Semin Respir Infect 11:244–251

    PubMed  Google Scholar 

  3. Griffith DE, Aksamit T, Brown-Elliott BA et al (2007) An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med 175:367–416

    PubMed  Article  CAS  Google Scholar 

  4. Haverkamp MH, Dissel JT van, Holland SM (2006) Human host genetic factors in nontuberculous mycobacterial infection: lessons from single gene disorders affecting innate and adaptive immunity and lessons from molecular defects in interferon-gamma-dependent signaling. Microbes Infect 8:1157–1166

    PubMed  Article  CAS  Google Scholar 

  5. Gruenheid S, Pinner E, Desjardins M, Gros P (1997) Natural resistance to infection with intracellular pathogens: the Nramp1 protein is recruited to the membrane of the phagosome. J Exp Med 185:717–730

    PubMed  Article  CAS  Google Scholar 

  6. Koh WJ, Kwon OJ, Kim EJ et al (2005) NRAMP1 gene polymorphism and susceptibility to nontuberculous mycobacterial lung diseases. Chest 128:94–101

    PubMed  Article  CAS  Google Scholar 

  7. Chan ED, Bai X, Kartalija M, Orme IM, Ordway DJ (2010) Host immune response to rapidly growing mycobacteria, an emerging cause of chronic lung disease. Am J Respir Cell Mol Biol 43:387–393

    PubMed  Article  CAS  Google Scholar 

  8. Casanova JL, Abel L (2002) Genetic dissection of immunity to mycobacteria: the human model. Annu Rev Immunol 20:581–620

    PubMed  Article  CAS  Google Scholar 

  9. Dorman SE, Holland SM (2000) Interferon-gamma and interleukin-12 pathway defects and human disease. Cytokine Growth Factor Rev 11:321–333

    PubMed  Article  CAS  Google Scholar 

  10. Kristensen IA, Veirum JE, Moller BK, Christiansen M (2011) Novel STAT1 alleles in a patient with impaired resistance to mycobacteria. J Clin Immunol 31:265–271

    PubMed  Article  Google Scholar 

  11. Hoflich C, Sabat R, Rosseau S et al (2004) Naturally occurring anti-IFN-gamma autoantibody and severe infections with Mycobacterium cheloneae and Burkholderia cocovenenans. Blood 103:673–675

    PubMed  Article  Google Scholar 

  12. Koya T, Tsubata C, Kagamu H et al (2009) Anti-interferon-gamma autoantibody in a patient with disseminated Mycobacterium avium complex. J Infect Chemother 15:118–122

    PubMed  Article  Google Scholar 

  13. Frucht DM, Holland SM (1996) Defective monocyte costimulation for IFN-gamma production in familial disseminated Mycobacterium avium complex infection: abnormal IL-12 regulation. J Immunol 157:411–416

    PubMed  CAS  Google Scholar 

  14. Colombo RE, Hill SC, Claypool RJ et al (2010) Familial clustering of pulmonary nontuberculous mycobacterial disease. Chest 137:629–634

    PubMed  Article  Google Scholar 

  15. Brener ZZ, Zhuravenko I, Bergman M (2009) Acute kidney injury in a patient with nontuberculous mycobacterial infections: a case report. Cases J 2:83

    PubMed  Article  Google Scholar 

  16. Olivier KN, Weber DJ, Lee JH et al (2003) Nontuberculous mycobacteria. II: nested-cohort study of impact on cystic fibrosis lung disease. Am J Respir Crit Care Med 167:835–840

    PubMed  Article  Google Scholar 

  17. Roux AL, Catherinot E, Ripoll F et al (2009) Multicenter study of prevalence of nontuberculous mycobacteria in patients with cystic fibrosis in France. J Clin Microbiol 47:4124–4128

    PubMed  Article  Google Scholar 

  18. Kim JS, Tanaka N, Newell JD et al (2005) Nontuberculous mycobacterial infection: CT scan findings, genotype, and treatment responsiveness. Chest 128:3863–3869

    PubMed  Article  Google Scholar 

  19. Horwitz ME, Uzel G, Linton GF et al (2003) Persistent Mycobacterium avium infection following nonmyeloablative allogeneic peripheral blood stem cell transplantation for interferon-gamma receptor-1 deficiency. Blood 102:2692–2694

    PubMed  Article  CAS  Google Scholar 

  20. Haverkamp MH, Lindeboom JA, Visser AW de et al (2010) Nontuberculous mycobacterial cervicofacial lymphadenitis in children from the multicenter, randomized, controlled trial in The Netherlands: relevance of polymorphisms in candidate host immunity genes. Int J Pediatr Otorhinolaryngol 74:752–754

    PubMed  Article  Google Scholar 

  21. Chan ED, Iseman MD (2010) Slender, older women appear to be more susceptible to nontuberculous mycobacterial lung disease. Gend Med 7:5–18

    PubMed  Article  Google Scholar 

  22. Winthrop KL, Chang E, Yamashita S et al (2009) Nontuberculous mycobacteria infections and anti-tumor necrosis factor-alpha therapy. Emerg Infect Dis 15:1556–1561

    PubMed  CAS  Google Scholar 

  23. Lutt JR, Pisculli ML, Weinblatt ME et al (2008) Severe nontuberculous mycobacterial infection in 2 patients receiving rituximab for refractory myositis. J Rheumatol 35:1683–1685

    PubMed  Google Scholar 

  24. Patel R, Roberts GD, Keating MR, Paya CV (1994) Infections due to nontuberculous mycobacteria in kidney, heart, and liver transplant recipients. Clin Infect Dis 19:263–273

    PubMed  Article  CAS  Google Scholar 

  25. Malouf MA, Glanville AR (1999) The spectrum of mycobacterial infection after lung transplantation. Am J Respir Crit Care Med 160:1611–1616

    PubMed  CAS  Google Scholar 

  26. Hadjiliadis D (2007) Special considerations for patients with cystic fibrosis undergoing lung transplantation. Chest 131:1224–1231

    PubMed  Article  Google Scholar 

  27. Ingram CW, Tanner DC, Durack DT et al (1993) Disseminated infection with rapidly growing mycobacteria. Clin Infect Dis 16:463–471

    PubMed  Article  CAS  Google Scholar 

  28. Horsburgh CR Jr, Gettings J, Alexander LN, Lennox JL (2001) Disseminated Mycobacterium avium complex disease among patients infected with human immunodeficiency virus, 1985–2000. Clin Infect Dis 33:1938–1943

    PubMed  Article  Google Scholar 

  29. Lai CC, Lee LN, Ding LW et al (2006) Emergence of disseminated infections due to nontuberculous mycobacteria in non-HIV-infected patients, including immunocompetent and immunocompromised patients in a university hospital in Taiwan. J Infect 53:77–84

    PubMed  Article  Google Scholar 

  30. Ferreira RM, Saad MH, Silva MG, Fonseca LS (2002) Non-tuberculous mycobacteria I: one year clinical isolates identification in Tertiary Hospital Aids Reference Center, Rio de Janeiro, Brazil, in pre highly active antiretroviral therapy era. Mem Inst Oswaldo Cruz 97:725–729

    PubMed  Article  Google Scholar 

  31. Williams PL, Currier JS, Swindells S (1999) Joint effects of HIV-1 RNA levels and CD4 lymphocyte cells on the risk of specific opportunistic infections. AIDS 13:1035–1044

    PubMed  Article  CAS  Google Scholar 

  32. Manosuthi W, Chaovavanich A, Tansuphaswadikul S et al (2007) Incidence and risk factors of major opportunistic infections after initiation of antiretroviral therapy among advanced HIV-infected patients in a resource-limited setting. J Infect 55:464–469

    PubMed  Article  Google Scholar 

  33. Lin RJ, Song J (2011) An unusual cause of chest pain: Mycobacterium avium complex and the immune reconstitution inflammatory syndrome. J Hosp Med 6:309–311

    PubMed  Article  Google Scholar 

  34. Huiras E, Preda V, Maurer T, Whitfeld M (2008) Cutaneous manifestations of immune reconstitution inflammatory syndrome. Curr Opin HIV AIDS 3:453–460

    PubMed  Article  Google Scholar 

  35. Kim HC, Bae IG, Ma JE et al (2007) Mycobacterium avium complex infection presenting as an endobronchial mass in a patient with acquired immune deficiency syndrome. Korean J Intern Med 22:215–219

    PubMed  Article  Google Scholar 

  36. Packer SJ, Cesario T, Williams JH Jr (1988) Mycobacterium avium complex infection presenting as endobronchial lesions in immunosuppressed patients. Ann Intern Med 109:389–393

    PubMed  CAS  Google Scholar 

  37. Lazaro E, Coureau G, Guedj J et al (2006) Change in T-lymphocyte count after initiation of highly active antiretroviral therapy in HIV-infected patients with history of Mycobacterium avium complex infection. Antivir Ther 11:343–350

    PubMed  CAS  Google Scholar 

  38. Chandra RK, Kumari S (1994) Effects of nutrition on the immune system. Nutrition 10:207–210

    PubMed  CAS  Google Scholar 

  39. Nova E, Samartin S, Gomez S et al (2002) The adaptive response of the immune system to the particular malnutrition of eating disorders. Eur J Clin Nutr 56(Suppl 3):S34–S37

    PubMed  Article  CAS  Google Scholar 

  40. Kim RD, Greenberg DE, Ehrmantraut ME et al (2008) Pulmonary nontuberculous mycobacterial disease: prospective study of a distinct preexisting syndrome. Am J Respir Crit Care Med 178:1066–1074

    PubMed  Article  CAS  Google Scholar 

  41. Brogden RN, Fitton A (1994) Rifabutin. A review of its antimicrobial activity, pharmacokinetic properties and therapeutic efficacy. Drugs 47:983–1009

    PubMed  Article  CAS  Google Scholar 

  42. Weiner M, Benator D, Peloquin CA et al (2005) Evaluation of the drug interaction between rifabutin and efavirenz in patients with HIV infection and tuberculosis. Clin Infect Dis 41:1343–1349

    PubMed  Article  CAS  Google Scholar 

  43. Ward CM, Jyonouchi H, Kotenko SV et al (2007) Adjunctive treatment of disseminated Mycobacterium avium complex infection with interferon alpha-2b in a patient with complete interferon-gamma receptor R1 deficiency. Eur J Pediatr 166:981–985

    PubMed  Article  CAS  Google Scholar 

  44. Hussein Z, Landt O, Wirths B, Wellinghausen N (2009) Detection of non-tuberculous mycobacteria in hospital water by culture and molecular methods. Int J Med Microbiol 299:281–290

    PubMed  Article  CAS  Google Scholar 

  45. Maslow JN, Brar I, Smith G et al (2003) Latent infection as a source of disseminated disease caused by organisms of the Mycobacterium avium complex in simian immunodeficiency virus-infected rhesus macaques. J Infect Dis 187:1748–1755

    PubMed  Article  Google Scholar 

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Authors and Affiliations

  1. Medizinische Klinik III/Infektiologie, Universitätsklinikum Schleswig-Holstein Campus Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Deutschland

    J. Rupp

  2. Institut für Medizinische Mikrobiologie und Hygiene, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck, Deutschland

    J. Rupp

  3. Medizinische Klinik Nord, Pneumologie/Infektiologie, Klinikum Dortmund gGmbH, Dortmund, Deutschland

    B. Schaaf

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Rupp, J., Schaaf, B. Infektionen mit nichttuberkulösen Mykobakterien bei Patienten mit Immundefekten. Pneumologe 8, 412–417 (2011). https://doi.org/10.1007/s10405-011-0486-6

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Schlüsselwörter

  • Immundefekte
  • Nichttuberkulöse Mykobakterien
  • Biologicals
  • HIV
  • Aids

Keywords

  • Immune deficiencies
  • Nontuberculous mycobacteria
  • Biologicals
  • HIV
  • AIDS