Treatment outcomes for Mycobacterium avium complex: a systematic review and meta-analysis

  • H.-B. Xu
  • R.-H. Jiang
  • L. Li


To evaluate the existing evidence regarding treatment regimens for Mycobacterium avium complex (MAC), a systematic review of the available therapeutic studies was conducted to assess treatment outcomes. A random-effects meta-analysis was used to assess treatment outcomes. Subgroup analyses were also conducted by separating studies based on each characteristic independently. Twenty-eight trials met the inclusion criteria. Our meta-analysis showed that the estimated pooled treatment success rate for patients with MAC disease was 39 % [95 % confidence interval (CI) 38–41 %]. The rates of failure, relapse, death, and default were 27 % (95 % CI 25–29 %), 6 % (95 % CI 5–7 %), 17 % (95 % CI 15–18 %), and 12 % (95 % CI 11–13 %), respectively. The proportion of patients treated successfully did not differ significantly on the basis of the study characteristics. However, studies with treatment regimens containing macrolides had significantly higher pooled success proportions (42 %, 95 % CI 40–44 %) than that of other studies (28 %, 95 % CI 24–32 %). Substantial heterogeneity in the study characteristics prevented more conclusive determination of what factors had the greatest effect on the proportion of patients that achieve treatment success and limited the validity of this analysis. This review underscored the importance of strong patient support and treatment follow-up systems to develop successful MAC treatment programs.


Macrolides Human Immunodeficiency Virus Patient Mycobacterium Avium Complex Nontuberculous Mycobacterium Assess Treatment Outcome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We thank all the patients who had been treated in these trials.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Griffith DE, Aksamit T, Brown-Elliott BA, Catanzaro A, Daley C, Gordin F, Holland SM, Horsburgh R, Huitt G, Iademarco MF, Iseman M, Olivier K, Ruoss S, von Reyn CF, Wallace RJ Jr, Winthrop K; ATS Mycobacterial Diseases Subcommittee; American Thoracic Society; Infectious Disease Society of America (2007) An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med 175:367–416PubMedCrossRefGoogle Scholar
  2. 2.
    Martín-Casabona N, Bahrmand AR, Bennedsen J, Thomsen VO, Curcio M, Fauville-Dufaux M, Feldman K, Havelkova M, Katila ML, Köksalan K, Pereira MF, Rodrigues F, Pfyffer GE, Portaels F, Urgell JR, Rüsch-Gerdes S, Tortoli E, Vincent V, Watt B; Spanish Group for Non-Tuberculosis Mycobacteria (2004) Non-tuberculous mycobacteria: patterns of isolation. A multi-country retrospective survey. Int J Tuberc Lung Dis 8:1186–1193PubMedGoogle Scholar
  3. 3.
    Henry MT, Inamdar L, O’Riordain D, Schweiger M, Watson JP (2004) Nontuberculous mycobacteria in non-HIV patients: epidemiology, treatment and response. Eur Respir J 23:741–746PubMedCrossRefGoogle Scholar
  4. 4.
    Simons S, van Ingen J, Hsueh PR, van Hung N, Dekhuijzen PN, Boeree MJ, van Soolingen D (2011) Nontuberculous mycobacteria in respiratory tract infections, eastern Asia. Emerg Infect Dis 17:343–349PubMedCrossRefGoogle Scholar
  5. 5.
    Horsburgh CR Jr (1996) Epidemiology of Mycobacterium avium complex. In: Korvick JA, Benson CA (eds) Mycobacterium avium complex infection: progress in research and treatment. Marcel Dekker, New York, pp 1–22Google Scholar
  6. 6.
    Wang HX, Yue J, Han M, Yang JH, Gao RL, Jing LJ, Yang SS, Zhao YL (2010) Nontuberculous mycobacteria: susceptibility pattern and prevalence rate in Shanghai from 2005 to 2008. Chin Med J 123:184–187PubMedGoogle Scholar
  7. 7.
    Griffith DE (1999) Risk–benefit assessment of therapies for Mycobacterium avium complex infections. Drug Saf 21:137–152PubMedCrossRefGoogle Scholar
  8. 8.
    Moher D, Cook DJ, Eastwood S, Olkin I, Rennie D, Stroup DF (1999) Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of Reporting of Meta-analyses. Lancet 354:1896–1900PubMedCrossRefGoogle Scholar
  9. 9.
    American Thoracic Society (1997) Diagnosis and treatment of disease caused by nontuberculous mycobacteria. This official statement of the American Thoracic Society was approved by the Board of Directors, March 1997. Medical Section of the American Lung Association. Am J Respir Crit Care Med 156:S1–S25CrossRefGoogle Scholar
  10. 10.
    Gelman A, Carlin JB, Stern HS, Rubin DB (2003) Bayesian data analysis. CRC Press, Boca RatonGoogle Scholar
  11. 11.
    Brooks SP, Gelman A (1998) General methods for monitoring convergence of iterative simulations. J Comput Graph Stat 7:434–455Google Scholar
  12. 12.
    Higgins JPT, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560PubMedCrossRefGoogle Scholar
  13. 13.
    Chaisson RE, Benson CA, Dube MP, Heifets LB, Korvick JA, Elkin S, Smith T, Craft JC, Sattler FR (1994) Clarithromycin 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 121:905–911PubMedCrossRefGoogle Scholar
  14. 14.
    Research Committee of the British Thoracic Society (2001) First randomised trial of treatments for pulmonary disease caused by M avium intracellulare, M malmoense, and M xenopi in HIV negative patients: rifampicin, ethambutol and isoniazid versus rifampicin and ethambutol. Thorax 56:167–172CrossRefGoogle Scholar
  15. 15.
    Dautzenberg B, Piperno D, Diot P, Truffot-Pernot C, Chauvin JP (1995) Clarithromycin in the treatment of Mycobacterium avium lung infections in patients without AIDS. Clarithromycin Study Group of France. Chest 107:1035–1040PubMedCrossRefGoogle Scholar
  16. 16.
    Shafran SD, Singer J, Zarowny DP, Phillips P, Salit I, Walmsley SL, Fong IW, Gill MJ, Rachlis AR, Lalonde RG, Fanning MM, Tsoukas CM (1996) 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. N Engl J Med 335:377–383PubMedCrossRefGoogle Scholar
  17. 17.
    Chaisson RE, Keiser P, Pierce M, Fessel WJ, Ruskin J, Lahart C, Benson CA, Meek K, Siepman N, Craft JC (1997) Clarithromycin and ethambutol with or without clofazimine for the treatment of bacteremic Mycobacterium avium complex disease in patients with HIV infection. AIDS 11:311–317PubMedCrossRefGoogle Scholar
  18. 18.
    Dautzenberg B, Truffot-Pernot C, Hazebroucq J, Legris S, Guérin C, Begelman C, Guermonprez G, Fievet MH, Chastang C, Grosset J (1997) A randomized comparison of two clarithromycin doses for treatment of Mycobacterium avium complex infections. Infection 25:16–21PubMedCrossRefGoogle Scholar
  19. 19.
    Dubé MP, Sattler FR, Torriani FJ, See D, Havlir DV, Kemper CA, Dezfuli MG, Bozzette SA, Bartok AE, Leedom JM, Tilles JG, McCutchan JA (1997) A randomized evaluation of ethambutol for prevention of relapse and drug resistance during treatment of Mycobacterium avium complex bacteremia with clarithromycin-based combination therapy. California Collaborative Treatment Group. J Infect Dis 176:1225–1232PubMedCrossRefGoogle Scholar
  20. 20.
    Roussel G, Igual J (1998) Clarithromycin with minocycline and clofazimine for Mycobacterium avium intracellulare complex lung disease in patients without the acquired immune deficiency syndrome. GETIM. Groupe d’Etude et de Traitement des Infections à Mycobactéries. Int J Tuberc Lung Dis 2:462–470PubMedGoogle Scholar
  21. 21.
    Ward TT, Rimland D, Kauffman C, Huycke M, Evans TG, Heifets L (1998) Randomized, open-label trial of azithromycin plus ethambutol vs. clarithromycin plus ethambutol as therapy for Mycobacterium avium complex bacteremia in patients with human immunodeficiency virus infection. Veterans Affairs HIV Research Consortium. Clin Infect Dis 27:1278–1285PubMedCrossRefGoogle Scholar
  22. 22.
    Cohn DL, Fisher EJ, Peng GT, Hodges JS, Chesnut J, Child CC, Franchino B, Gibert CL, El-Sadr W, Hafner R, Korvick J, Ropka M, Heifets L, Clotfelter J, Munroe D, Horsburgh CR Jr (1999) A prospective randomized trial of four three-drug regimens in the treatment of disseminated Mycobacterium avium complex disease in AIDS patients: excess mortality associated with high-dose clarithromycin. Terry Beirn Community Programs for Clinical Research on AIDS. Clin Infect Dis 29:125–133PubMedCrossRefGoogle Scholar
  23. 23.
    Gordin FM, Sullam PM, Shafran SD, Cohn DL, Wynne B, Paxton L, Perry K, Horsburgh CR Jr (1999) A randomized, placebo-controlled study of rifabutin added to a regimen of clarithromycin and ethambutol for treatment of disseminated infection with Mycobacterium avium complex. Clin Infect Dis 28:1080–1085PubMedCrossRefGoogle Scholar
  24. 24.
    Fournier S, Burguière AM, Flahault A, Vincent V, Treilhou MP, Eliaszewicz M (1999) Effect of adding clofazimine to combined clarithromycin–ethambutol therapy for Mycobacterium avium complex septicemia in AIDS patients. Eur J Clin Microbiol Infect Dis 18:16–22PubMedCrossRefGoogle Scholar
  25. 25.
    Koletar SL, Berry AJ, Cynamon MH, Jacobson J, Currier JS, MacGregor RR, Dunne MW, Williams DJ (1999) Azithromycin as treatment for disseminated Mycobacterium avium complex in AIDS patients. Antimicrob Agents Chemother 43:2869–2872PubMedCentralPubMedGoogle Scholar
  26. 26.
    Roger PM, Carles M, Agussol-Foin I, Pandiani L, Keïta-Perse O, Mondain V, De Salvador F, Dellamonica P (1999) Efficacy and safety of an intravenous induction therapy for treatment of disseminated Mycobacterium avium complex infection in AIDS patients: a pilot study. J Antimicrob Chemother 44:129–131PubMedCrossRefGoogle Scholar
  27. 27.
    Tanaka E, Kimoto T, Tsuyuguchi K, Watanabe I, Matsumoto H, Niimi A, Suzuki K, Murayama T, Amitani R, Kuze F (1999) Effect of clarithromycin regimen for Mycobacterium avium complex pulmonary disease. Am J Respir Crit Care Med 160:866–872PubMedCrossRefGoogle Scholar
  28. 28.
    Dunne M, Fessel J, Kumar P, Dickenson G, Keiser P, Boulos M, Mogyros M, White AC Jr, Cahn P, O’Connor M, Lewi D, Green S, Tilles J, Hicks C, Bissett J, Schneider MM, Benner R (2000) A randomized, double-blind trial comparing azithromycin and clarithromycin in the treatment of disseminated Mycobacterium avium infection in patients with human immunodeficiency virus. Clin Infect Dis 31:1245–1252PubMedCrossRefGoogle Scholar
  29. 29.
    Griffith DE, Brown BA, Cegielski P, Murphy DT, Wallace RJ Jr (2000) Early results (at 6 months) with intermittent clarithromycin-including regimens for lung disease due to mycobacterium avium complex. Clin Infect Dis 30:288–292PubMedCrossRefGoogle Scholar
  30. 30.
    Benson CA, Williams PL, Currier JS, Holland F, Mahon LF, MacGregor RR, Inderlied CB, Flexner C, Neidig J, Chaisson R, Notario GF, Hafner R; AIDS Clinical Trials Group 223 Protocol Team (2003) A prospective, randomized trial examining the efficacy and safety of clarithromycin in combination with ethambutol, rifabutin, or both for the treatment of disseminated Mycobacterium avium complex disease in persons with acquired immunodeficiency syndrome. Infect Dis 37:1234–1243CrossRefGoogle Scholar
  31. 31.
    Jenkins PA, Campbell IA, Banks J, Gelder CM, Prescott RJ, Smith AP (2008) Clarithromycin vs ciprofloxacin as adjuncts to rifampicin and ethambutol in treating opportunist mycobacterial lung diseases and an assessment of Mycobacterium vaccae immunotherapy. Thorax 63:627–634PubMedCrossRefGoogle Scholar
  32. 32.
    Lam PK, Griffith DE, Aksamit TR, Ruoss SJ, Garay SM, Daley CL, Catanzaro A (2006) Factors related to response to intermittent treatment of Mycobacterium avium complex lung disease. Am J Respir Crit Care Med 173:1283–1289PubMedCrossRefGoogle Scholar
  33. 33.
    Kobashi Y, Matsushima T, Oka M (2007) A double-blind randomized study of aminoglycoside infusion with combined therapy for pulmonary Mycobacterium avium complex disease. Respir Med 101:130–138PubMedCrossRefGoogle Scholar
  34. 34.
    Jacobson MA, Yajko D, Northfelt D, Charlebois E, Gary D, Brosgart C, Sanders CA, Hadley WK (1993) Randomized, placebo-controlled trial of rifampin, ethambutol, and ciprofloxacin for AIDS patients with disseminated Mycobacterium avium complex infection. J Infect Dis 168:112–119PubMedCrossRefGoogle Scholar
  35. 35.
    Kemper CA, Havlir D, Haghighat D, Dubé M, Bartok AE, Sison JP, Yao YZ, Yangco B, Leedom JM, Tilles JG, Allen McCutchan J, Deresinski SC (1994) The individual microbiologic effect of three antimycobacterial agents, clofazimine, ethambutol, and rifampin, on Mycobacterium avium complex bacteremia in patients with AIDS. J Infect Dis 170:157–164PubMedCrossRefGoogle Scholar
  36. 36.
    Wallace RJ Jr, Brown BA, Griffith DE, Girard WM, Murphy DT (1996) Clarithromycin regimens for pulmonary Mycobacterium avium complex. The first 50 patients. Am J Respir Crit Care Med 153:1766–1772PubMedCrossRefGoogle Scholar
  37. 37.
    Ahn CH, Ahn SS, Anderson RA, Murphy DT, Mammo A (1986) A four-drug regimen for initial treatment of cavitary disease caused by Mycobacterium avium complex. Am Rev Respir Dis 134:438–441PubMedGoogle Scholar
  38. 38.
    Kemper CA, Meng TC, Nussbaum J, Chiu J, Feigal DF, Bartok AE, Leedom JM, Tilles JG, Deresinski SC, McCutchan JA (1992) Treatment of Mycobacterium avium complex bacteremia in AIDS with a four-drug oral regimen. Rifampin, ethambutol, clofazimine, and ciprofloxacin. The California Collaborative Treatment Group. Ann Intern Med 116:466–472PubMedCrossRefGoogle Scholar
  39. 39.
    Dautzenberg B, Castellani P, Pellegrin JL, Vittecoq D, Truffot-Pernot C, Pirotta N, Sassella D (1996) Early bactericidal activity of rifabutin versus that of placebo in treatment of disseminated Mycobacterium avium complex bacteremia in AIDS patients. Antimicrob Agents Chemother 40:1722–1725PubMedCentralPubMedGoogle Scholar
  40. 40.
    Dautzenberg B, Olliaro P, Ruf B, Esposito R, Opravil M, Hoy JF, Rozenbaum W, Carosi GP, Micoud M, L’Age M, Pirotta N, Sassella D (1996) Rifabutin versus placebo in combination with three drugs in the treatment of nontuberculous mycobacterial infection in patients with AIDS. Clin Infect Dis 22:705–708PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Department of Clinical Pharmacy, Shanghai Tenth People’s HospitalTongji University School of MedicineShanghaiChina
  2. 2.Department of Tuberculosis, Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiChina

Personalised recommendations