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Die disseminierte Infektion mit Mycobacterium avium complex (MAC) bei HIV-Infektion

Disseminated Infection with mycobacterium avium complex in patients with HIV-infection

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Zusammenfassung

□ Epidemiologie

Die MAC-Infektion ist eine der häufigsten opportunistischen Infektionen bei HIV-infizierten Patienten und tritt besonders bei stark eingeschränktem Immunsystem auf (CD4-Zellen<50/μl). Die Prognose der unbehandelten Erkrankung ist mit durchschnittlich fünf bis sechs Monaten sehr schlecht. Durch eine Therapie konnte bisher eine Lebensverlängerung von vier Monaten erreicht werden.

□ Klinik und Diagnostik

Leitsymptom der disseminierten MAC-Infektion ist Fieber, weitere Symptome sind Gewichtsverlust, Nachtschweiß, Lymphknotenschwellungen, Hepatosplenomegalie, Bauchschmerzen und eine Anämie. Die Diagnose wird in der Regel über den Nachweis des Erregers in der Blutkultur gestellt, die eine hohe Sensitivität hat. Weitere diagnostische Möglichkeiten bestehen in der Kultur des Knochenmarks sowie Biopsien des Magen-Darm-Traktes, von Lymphknoten und der Leber. Der Erregernachweis im Sputum oder Stuhl beweist nur eine Kolonisation, geht aber häufig einer disseminierten Infektion voraus.

□ Therapie

Eine Kombination bestehend aus Clarithromycin, Rifabutin und Ethambutol hat sich als wirksamste Therapieform erwiesen und muß inzwischen als Standardtherapie angesehen werden. Hauptsächliche Nebenwirkungen bestehen in einer Uveitis (Rifabutin), gastrointesinalen Störungen (Clarithromycin) und einer Leukopenie (Rifabutin). Ein häufig auftretendes klinisches Problem sind Interaktionen (vor allem des Rifabutins) mit Proteaseinhibitoren.

□ Prophylaxe

Eine wirksame medikamentöse Prophylaxe der MAC-Infektion ist mit Clarithromycin, Rifabutin und Azithromycin möglich. Obwohl für die Prophylaxe mit Clarithromycin sogar ein Überlebensvorteil nachgewiesen ist, hat sich eine Primärprophylaxe der MAC-Infektion noch nicht allgemein durchgesetzt. Hauptgründe hierfür sind unterschiedliche Inzidenzen in verschiedenen Ländern sowie Nebenwirkungen und Medikamenteninteraktionen der zur Verfügung stehenden Präparate.

□ Schlußfolgerung

Die MAC-Infektion ist eine häufige opportunistische Erkrankung im Endstadium der HIV-Infektion. Die antibiotische Kombinationstherapie mit Clarithromycin, Rifabutin und Ethambutol führt zu einer Besserung der Symptome und einer Lebensverlängerung. Eine medikamentöse Primärprophylaxe ist mit verschiedenen Regimen möglich. Sie hat sich jedoch wegen der unterschiedlichen epidemiologischen Situation in verschiedenen Ländern bisher nicht allgemein durchgesetzt.

Abstract

□ Epidemiology

Disseminated MAC-infection is one of the most frequent opportunistic infections occuring in HIV-infected patients. Severely immunocompromised patients with CD4-counts < 50 /μl are at greatest risk for the disease. Survival of untreated infection is very poor (5 to 6 months). With therapy survival is prolonged by about 4 months.

□ Clinical Presentation and Diagnostic Procedures

The leading symptom of MAC-infection is fever eventually accompanied by weight lost, night sweats, enlarged lymph nodes, hepatosplenomegaly, abdominal pain and anemia. Blood cultures are very sensitive and the most appropriate examination. Other diagnostic procedures include bone marrow cultures, biopsies of the gastrointestinal tract, lymph nodes and the liver. Detection of MAC in sputum and stool samples only proves colonisation but not dissemination. However, colonisation of the gastrointestinal tract frequently precedes disseminated disease.

□ Therapy

Combination of clarithromycin, rifabutin and ethambutol has proven to be the most efficacious therapy and therefore has to be considered as standard therapy for disseminted MAC-infection. Problems most frequently encountered with this medication include uveitis (rifabutin), gastrointestinal disturbances (clarithromycin) and leucopenia (rifabutin) as well as drug interactions with protease-inhibitors (rifabutin).

□ Prophylaxis

Clarithromycin, rifabutin and azithromycin given as primary prophylaxis can diminish the risk of disseminated MAC-infection. Although a survival benefit has been seen with clarithromycin, primary prophylaxis of MAC-infection is not standard care in many centers. Reasons to withhold MAC-prophylaxis include lower incidence rates in some countries as well as possible side effects and drug interactions.

□ Conclusion

Disseminated MAC-infection is a frequent opportunistic disease in HIV-infected persons who are severely immunocompromised. Antibiotic combination therapy with clarithromycin, rifabutin and ethambutol improves clinical symptoms and survival. Primary prophylaxis with different regimens is efficacious but the specific epidemiologic situation in each country has to be considered.

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Literatur

  1. Benson, C.: Disseminated mycobacterium avium complex disease in patients with AIDS. AIDS Res. hum. Retroviruses 10 (1994), 913–916.

    Article  PubMed  CAS  Google Scholar 

  2. Benson, C. A.: Disease due to the mycobacterium avium complex in patients with AIDS: epidemiology and clinical syndrome. Clin. infect. Dis. 18 (1994), S218–222.

    Google Scholar 

  3. Cappell, M. S., M. S. Schwartz, L. Biempica: Clinical utility of liver biopsy in patients with serum antibodies to the human immunodeficiency virus. Amer. J. Med. 88 (1990), 123–130.

    Article  PubMed  CAS  Google Scholar 

  4. Cato, A., J. H. Cavanaugh, H. Shi, A. Hsu, G. G. R., J. Leonard: Assessment of multiple doses of ritonavir on the pharmacokinetics of rifabutin. XI. International Conference on AIDS, Vancouver, July 7–12, 1996.

  5. Cavicchi, M., G. Pialoux, F. Carnot, C. Offredo, C. Romana, P. Deslandes, B. Dupont, P. Berthelot, S. Pol: Value of liver biopsy for the rapid diagnosis of infection in human immunodeficiency virus-infected patients who have unexplained fever and elevated serum levels of alkaline phosphatase or gamma-glutamyl transferase. Clin. infect. Dis. 20 (1995), 606–610.

    PubMed  CAS  Google Scholar 

  6. Chaisson, R. E., C. A. Benson, M. P. Dube, L. B. Heifets, J. A. Korvick, S. Elkin, T. Smith, J. C. Craft, F. R. Sattler: Clarthromycin therapy for bacteremic mycobacterium avium complex disease. A randomized, double-blind, dose-ranging study in patients with AIDS. AIDS Clinical Trials Group Protocol 157 Study Team. Ann. intern. Med. 121 (1994), 905–911.

    PubMed  CAS  Google Scholar 

  7. Cohn, D. L., C. A. Benson, P. Williams, T. Nevin, J. Korvick, R. Hafner, D. Bourland, E. Kopek, S. Becker, P. Hojczyk, P. Timmons, C. Child: A prospective, randomised, double-blind, comparative study of the safety and efficacy of clarithromycin versus rifabutin versus the combination for the prevention of mycobacterium avium complex bacteremia or disseminated MAC disease. XI. International Conference on AIDS, Vancouver, July 7–12, 1996.

  8. Cohn, D. L., E. Fisher, B. Franchino, J. Hodges, J. Chesnut, C. Child, C. Gilbert, W. El-Sadr, R. Hafner, M. Ropka, L. Heifets, J. Clotfelter, D. Munroe, R. Caldwell, K. Canady, C. Horsburgh: Comparison of two doses of clarithromycin in a randomized trial of four 3-drug regimens for treatment of disseminated mycobacterium avium complex disease in AIDS: excess mortality associated with high-dose clarithromycin. XI. International Conference on AIDS, Vancouver, July 7–12, 1996.

  9. Gray, J. R., L. Rabeneck: Atypical mycobacterial infection of the gastrointestinal tract in AIDS patients. Amer. J. Gastroenterol. 84 (1989), 1521–1524.

    CAS  Google Scholar 

  10. Havlir, D., F. Torriani, M. Dube: Uveitis associated with rifabutin prophylaxis. Ann. intern. Med. 121 (1994), 510–512.

    PubMed  CAS  Google Scholar 

  11. Havlir, D. V., M. P. Dube, F. R. Sattler, D. N. Forthal, C. A. Kemper, M. W. Dunne, D. M. Parenti, J. P. Lavelle, A. C. White Jr, M. D. Witt, S. A. Bozzette, J. A. McCutchan: Prophylaxis against disseminated mycobacterium avium complex with weekly azithromycin, daily rifabutin, or both. Califorma Collaborative Treatment Group. New Engl. J. Med. 335 (1996), 392–398.

    Article  PubMed  CAS  Google Scholar 

  12. Hawkins, C. C., J. W. Gold, E. Whimbey, T. E. Kiehn, P. Brannon, R. Cammarata, A. E. Brown, D. Armstrong: Mycobacterium avium complex infections in patients with the acquired immunodeficiency syndrome. Ann. intern. Med. 105 (1986), 184–188.

    PubMed  CAS  Google Scholar 

  13. Horsburgh, C. R. Jr: Mycobacterium avium complex infection in the acquired immunodeficiency syndrome. New Engl. J. Med. 324 (1991), 1332–1338.

    PubMed  Google Scholar 

  14. Horsburgh, C. R. Jr, J. A. Havlik, D. A. Ellis, E. Kennedy, S. A. Fann, R. E. Dubois, S. E. Thompson: Survival of patients with acquired immune deficiency syndrome and disseminated mycobacterium avium complex infection with and without antimycobacterial chemotherapy. Amer. Rev. resp. Dis. 144 (1991), 557–559.

    PubMed  Google Scholar 

  15. Horsburgh, C. R. Jr, B. Metchock, S. M. Gordon, I. A. Havlik Jr, J. E. McGowan Jr, S. E. R. Thompson: Predictors of survival in patients with AIDS and disseminated mycobacterium avium complex disease. J. infect. Dis. 170 (1994), 573–577.

    PubMed  Google Scholar 

  16. Horsburgh, C. R. Jr, B. G. Metchock, J. E. McGowan Jr, S. E. Thompson: Clinical implications of recovery of mycobacterium avium complex from the stool or respiratory tract of HIV-infected individuals [letter]. Aids 6 (1992), 512–514.

    PubMed  Google Scholar 

  17. Ives, D. V., R. B. Davis, J. S. Currier: Impact of clarithromycin and azithromycin on patterns of treatment and survival among AIDS patients with disseminated mycobacterium avium complex. Aids 9 (1995), 261–266.

    Article  PubMed  CAS  Google Scholar 

  18. Jacobson, M. A., P. C. Hopewell, D. M. Yajko, W. K. Hadley, E. Lazarus, P. K. Mohanty, G. W. Modin, D. W. Feigal, P. S. Cusick, M. A. Sande: Natural history of disseminated mycobacterium avium complex infection in AIDS. J. infect. Dis. 164 (1991), 994–998.

    PubMed  CAS  Google Scholar 

  19. Katz, M. H., N. A. Hessol, S. P. Buchbinder, A. Hirozawa, P. O’Malley, S. D. Holmberg: Temporal trends of opportunistic infections and malignancies in homosexual men with AIDS. J. infect. Dis. 170 (1994), 198–202.

    PubMed  CAS  Google Scholar 

  20. Kemper, C. A., S. C. Deresinski: Mycobacterium avium complex infection in AIDS. AIDS clin. Rev. 96 (1995), 153–228.

    Google Scholar 

  21. Koch-Institut, R.: AIDS/HIV Quartalsbericht IV/96, 1996.

  22. Modilevsky, T., F. R. Sattler, P. F. Barnes: Mycobacterial disease in patients with human immunodeficiency virus infection. Arch. intern. Med. 149 (1989), 2201–2205.

    Article  PubMed  CAS  Google Scholar 

  23. Moore, R. D., R. E. Chaisson: Natural history of opportunistic disease in an HIV-infected urban clinical cohort. Ann. intern. Med. 124 (1996), 633–642.

    PubMed  CAS  Google Scholar 

  24. Moore, R. D., R. E. Chaisson: Survival analysis of two controlled trials of rifabutin prophylaxis against mycobacterium avium complex in AIDS. Aids 9 (1995), 1337–1342.

    Article  PubMed  CAS  Google Scholar 

  25. Narang, P. K., C. B. Trapnell, J. R. Schoenfelder, J. P. Lavelle, J. R. Bianchine: Fluconazole and enhanced effect of rifabutin prophylaxis [letter; comment]. New Engl. J. Med. 330 (1994), 1316–1317.

    Article  PubMed  CAS  Google Scholar 

  26. Nightingale, S. D.: Ritabutin prophylaxis against mycobacterium avium complex infection [letter; comment]. Lancet 345 (1995), 265.

    Article  PubMed  CAS  Google Scholar 

  27. Nightingale, S. D., L. T. Byrd, P. M. Southern, J. D. Jockusch, S. X. Cal, B. A. Wynne: Incidence of mycobacterium avium-intracellulare complex bacteremia in human immunodeficiency virus-positive patients. J. infect. Dis. 165 (1992), 1082–1085.

    PubMed  CAS  Google Scholar 

  28. Northfelt, D. W., A. Mayer, L. D. Kaplan, D. I. Abrams, W. K. Hadley, D. M. Yajko, B. G. Herndier: The usefulness of diagnostic bone marrow examination in patients with human immunodeficiency virus (HIV) infection. J. acquir. Immun. Def. Syndr. 4 (1991), 659–666.

    CAS  Google Scholar 

  29. Peters, M., C. Muller, S. Rusch-Gerdes, C. Seidel, U. Gobel, H. D. Pohle, B. Ruf: Isolation of atypical mycobacteria from tap water in hospitals and homes: is this a possible source of disseminated MAC infection in AIDS patients? J. Infect. 31 (1995), 39–44.

    Article  PubMed  CAS  Google Scholar 

  30. Pierce, M., S. Crampton, D. Henry, L. Heifets, A. La Marca, M. Montecalvo, G. P. Wormser, H. Jablonowski, J. Jemsek, M. Cynamon, B. G. Yangco, G. Notario, J. C. Craft: A randomized trial of clarithromycin as prophylaxis against disseminated mycobacterium avium complex infection in patients with advanced acquired immunodeficiency syndrome. New Engl. J. Med. 335 (1996), 384–391.

    Article  PubMed  CAS  Google Scholar 

  31. Roger, P. M., V. Mondain, M. C. Saint Paul, M. Carles, B. Taillan, J. G. Fuzibet, J. F. Michiels, P. Dujardin, P. Dellamonica: Liver biopsy is not useful in the diagnosis of mycobacterial infections in patients who are infected with human immunodeficiency virus. Clin. infect. Dis. 23 (1996), 1302–1304.

    PubMed  CAS  Google Scholar 

  32. Rubin, D. S., J. J. Rahal: Mycobacterium-avium complex. Infect. Dis. Clin. N. Amer. 8 (1994), 413–426.

    CAS  Google Scholar 

  33. Shafran, S. D., J. Singer, D. P. Zarowny, P. Phillips, I. Salit, S. L. Walmsley, I. W. Fong, M. J. Gill, A. R. Rachlis, R. G. Lalonde, M. M. Fanning, C. M. Tsoukas: A comparison of two regimens for the treatment of mycobacterium avium complex bacteremia in AIDS: rifabutin, ethambutol, and clarithromycin versus rifampin, ethambutol, clofazimine, and ciprofloxacin. Canadian HIV Trials Network Protocol 010 Study Group. New Engl. J. Med. 335 (1996), 377–383.

    Article  PubMed  CAS  Google Scholar 

  34. Sison, J. P., Y. Yao, C. A. Kemper, J. R. Hamilton, E. Brummer, D. A. Stevens, S. C. Deresinski: Treatment of mycobacterium avium complex infection: do the results of in vitro susceptibility tests predict therapeutic outcome in human? J. infect. Dis. 173 (1996), 677–683.

    PubMed  CAS  Google Scholar 

  35. Sullam, P. M., F. M. Gordin, B. A. Wynne: Efficacy of rifabutin in the treatment of disseminated infection due to mycobacterium avium complex. The Rifabutin Treatment Group. Clin. infect. Dis. 19 (1994), 84–86.

    PubMed  CAS  Google Scholar 

  36. The Indinavir (MK 639) Pharmacokinetic Study Group, M. R. L., Jefferson Med. Coll. (US), SUNY Stony Brook (US), Robert Wood Johnson Med. School (US), St. Pierre Univ. Hospital (BEL): Indinavir (MK 639) Drug Interaction Studies. XI. International Conference on AIDS, Vancouver, July 7–12, 1996.

  37. Uribe-Botero, G., J. G. Prichard, H. J. Kaplowitz: Bone marrow in HIV infection. A comparison of fluorescent staining and cultures in the detection of mycobacteria. Amer. J. clin. Pathol. 91 (1989), 313–315.

    CAS  Google Scholar 

  38. USPHS/IDSA: USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus: a summary. Morb. Mortal wkly. Rep. 44 (1995), 1–34.

    Google Scholar 

  39. Wallace, J. M., J. B. Hannah: Mycobacterium avium complex infection in patients with the acquired immunodeficiency syndrome. A clinicopathologic study. Chest 93 (1988), 926–932.

    Article  PubMed  CAS  Google Scholar 

  40. Wallace, R. J. Jr, B. A. Brown, D. E. Griffith, W. Girard, K. Tanaka: Reduced serum levels of clarithromycin in patients treated with multidrug regimens including rifampin or rifabutin for mycobacterium avium-m. intracellulare infection. J. infect. Dis. 171 (1995), 747–750.

    PubMed  Google Scholar 

  41. Yajko, D. M., D. P. Chin, P. C. Gonzalez, P. S. Nassos, P. C. Hopewell, A. L. Reingold, C. R. Horsburgh Jr, M. A. Yakrus, S. M. Ostroff, W. K. Hadley: Mycobacterium avium complex in water, food, and soil samples collected from the environment of HIV-infected individuals. J. acquir. Immun. Def. Syndr. hum. Retrovirol. 9 (1995), 176–182.

    CAS  Google Scholar 

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  1. Klinik I für Innere Medizin der Universität, Joseph-Stelzmann-Straße 9, D-50924, Köln

    Gerd Fätkenheuer, Bernd Salzberger & Volker Diehl

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  1. Gerd Fätkenheuer
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  2. Bernd Salzberger
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Fätkenheuer, G., Salzberger, B. & Diehl, V. Die disseminierte Infektion mit Mycobacterium avium complex (MAC) bei HIV-Infektion. Med Klin 93, 360–364 (1998). https://doi.org/10.1007/BF03044680

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