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

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Abstract

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.

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References

  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 175:367–416

    Article  CAS  PubMed  Google Scholar 

  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 8:1186–1193

    PubMed  Google Scholar 

  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 23:741–746

    Article  CAS  PubMed  Google Scholar 

  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 17:343–349

    Article  PubMed  Google Scholar 

  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 1–22

    Google Scholar 

  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 123:184–187

    PubMed  Google Scholar 

  7. Griffith DE (1999) Risk–benefit assessment of therapies for Mycobacterium avium complex infections. Drug Saf 21:137–152

    Article  CAS  PubMed  Google Scholar 

  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 354:1896–1900

    Article  CAS  PubMed  Google Scholar 

  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–S25

    Article  Google Scholar 

  10. Gelman A, Carlin JB, Stern HS, Rubin DB (2003) Bayesian data analysis. CRC Press, Boca Raton

    Google Scholar 

  11. Brooks SP, Gelman A (1998) General methods for monitoring convergence of iterative simulations. J Comput Graph Stat 7:434–455

    Google Scholar 

  12. Higgins JPT, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560

    Article  PubMed  Google Scholar 

  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 121:905–911

    Article  CAS  PubMed  Google Scholar 

  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 56:167–172

    Article  Google Scholar 

  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 107:1035–1040

    Article  CAS  PubMed  Google Scholar 

  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 335:377–383

    Article  CAS  PubMed  Google Scholar 

  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 11:311–317

    Article  CAS  PubMed  Google Scholar 

  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 25:16–21

    Article  CAS  PubMed  Google Scholar 

  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 176:1225–1232

    Article  PubMed  Google Scholar 

  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 2:462–470

    CAS  PubMed  Google Scholar 

  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 27:1278–1285

    Article  CAS  PubMed  Google Scholar 

  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 29:125–133

    Article  CAS  PubMed  Google Scholar 

  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 28:1080–1085

    Article  CAS  PubMed  Google Scholar 

  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 18:16–22

    Article  CAS  PubMed  Google Scholar 

  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 43:2869–2872

    CAS  PubMed Central  PubMed  Google Scholar 

  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 44:129–131

    Article  CAS  PubMed  Google Scholar 

  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 160:866–872

    Article  CAS  PubMed  Google Scholar 

  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 31:1245–1252

    Article  CAS  PubMed  Google Scholar 

  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 30:288–292

    Article  CAS  PubMed  Google Scholar 

  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 37:1234–1243

    Article  CAS  Google Scholar 

  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 63:627–634

    Article  CAS  PubMed  Google Scholar 

  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 173:1283–1289

    Article  CAS  PubMed  Google Scholar 

  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 101:130–138

    Article  PubMed  Google Scholar 

  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 168:112–119

    Article  CAS  PubMed  Google Scholar 

  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 170:157–164

    Article  CAS  PubMed  Google Scholar 

  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 153:1766–1772

    Article  PubMed  Google Scholar 

  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 134:438–441

    CAS  PubMed  Google Scholar 

  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 116:466–472

    Article  CAS  PubMed  Google Scholar 

  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 40:1722–1725

    CAS  PubMed Central  PubMed  Google Scholar 

  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 22:705–708

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

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.

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Authors and Affiliations

  1. Department of Clinical Pharmacy, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, China

    H.-B. Xu & L. Li

  2. Department of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China

    R.-H. Jiang

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  1. H.-B. Xu
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Correspondence to H.-B. Xu.

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Hong-Bin Xu and Rui-Hua Jiang have equally contributed to this article.

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Xu, HB., Jiang, RH. & Li, L. Treatment outcomes for Mycobacterium avium complex: a systematic review and meta-analysis. Eur J Clin Microbiol Infect Dis 33, 347–358 (2014). https://doi.org/10.1007/s10096-013-1962-1

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