Abstract
DisseminatedMycobacterium avium complex (MAC) is one of the most common opportunistic infections in AIDS patients and is increasingly recognized as a significant pathogen in chronic pulmonary disease in nonimmunocompromised patients. Important progress in therapy has occurred over the last several years. In AIDS patients, multidrug therapy has been shown to be beneficial in terms of reducing circulating bacteremia and improving clinical symptoms. Clarithromycin and azithromycin, two broad-spectrum antimicrobials with minimal activity againstMycobacterium tuberculosis, have emerged as potent, well tolerated agents pivotal to treatment regimens. In AIDS patients, rifabutin prophylaxis reduced the frequency of MAC bacteremia by 50 % in two placebo controlled trials. Despite these advances, there remains a need for determining the optimal combination regimens for therapy, and more effective drugs for prophylaxis which are beneficial both in terms of survival and functional capacity of patients.
Similar content being viewed by others
References
Wolinsky E Nontuberculous mycobacteria and associated diseases. American Review of Respiratory Diseases 1979, 119: 107–159.
Inderlied CB, Kemper CA, Bermudez LEM TheMycobacterium avium complex. Clinical Microbiology Reviews 1993, 6: 266–310.
Horsburgh CRJ Mycobacterium avium complex infection in the acquired immunodeficiency syndrome. New England Journal of Medicine 1991, 324: 1332–1338.
Prince DS, Peterson DD, Steiner RM, Gottlieb JE, Scott R, Israel HL, Figueroa WG, Fish JE Infection withMycobacterium avium complex in patients without predisposing conditions. New England Journal of Medicine 1989, 321: 863–868.
Denner JC, Tsang AY, Chatterjee D, Brennan PJ Comprehensive approach to identification of serovars ofMycobacterium avium complex. Journal of Clinical Microbiology 1992, 30: 473–478.
Saito H, Tomioka H, Sato H, Tasaka H, Dawson DJ Identification of various serovar strains ofMycobacterium avium complex by using DNA probes specific forMycobacterium avium andMycobacterium intracellulare. Journal of Clinical Microbiology 1990, 28: 1694–1697.
Corpe RF Clinical aspects, medical and surgical, in the management of Battey-type pulmonary disease. Diseases of the Chest 1964, 45: 380–382.
Guthertz LS, Damsker B, Bottone EJ, Ford EG, Midura TF, Janda JM Mycobacterium avium andMycobacterium intracellulare infections in patients with and without AIDS. Journal of Infectious Diseases 1989, 160: 1037–1041.
Kiehn TE, Edwards FF, Brannon P, Tsang AY, Maio M, Gold JW, Whimbey E, Wong B, McClatchy JK, Armstrong D Infections caused byMycobacterium avium complex in immunocompromised patients: diagnosis by blood culture and fecal examination, antimicrobial susceptibility tests, and morphological and seroagglutination characteristics. Journal of Clinical Microbiology 1985, 21: 168–173.
McNeil MR, Brennan PJ Structure, function and biogenesis of the cell envelope of mycobacteria in relation to bacterial physiology, pathogenesis and drug resistance; some thoughts and possibilities arising from recent structural information. Research in Microbiology 1991, 142: 451–463.
Rastogi N, Frehel C, Ryter A, Ohayon H, Lesourd M, David HL Multiple drug resistance inMycobacterium avium: is the wall architecture responsible for exclusion of antimicrobial agents? Antimicrobial Agents and Chemotherapy 1981, 20: 666–677.
Schaefer WB, Davis CL, Cohn ML Pathogenicity of transparent, opaque, and rough variants ofMycobacterium avium in chickens and mice. American Review of Respiratory Diseases 1970, 102: 499–506.
Meylan PR, Richman DD, Kornbluth RS Characterization and growth in human macrophages ofMycobacterium avium complex strains isolated from the blood of patients with acquired immunodeficiency syndrome. Infection and Immunology 1990, 58: 2564–2568.
McCarthy C, Ashbaugh P Factors that affect the cell cycle ofMycobacterium avium. Reviews in Infectious Diseases 1981, 3: 914–925.
Shiratsuchi H, Johnson JL, Ellner JJ Bidirectional effects of cytokines on the growth ofMycobacterium avium within human monocytes. Journal of Immunology 1991, 146: 3165–3170.
Bermudez LE, Young LS, Enkel H Interaction ofMycobacterium avium complex with human macrophages: roles of membrane receptors and serum proteins. Infection and Immunology 1991, 59: 1697–1702.
Blanchard DK, Michelini-Norris MB, Pearson CA, McMillen S, Djeu JY Production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by monocytes and large granular lymphocytes stimulated withMycobacterium avium — M. intracellulare: activation of bactericidal activity by GM-CSF. Infection and Immunology 1991, 59: 2396–2402.
Bermudez LE Production of transforming growth factor-beta byMycobacterium avium-infected human macrophages is associated with unresponsiveness to IFN-gamma. Journal of Immunology 1993, 150: 1838–1845.
Katz P, Yeager H, Whalen G, Evans M, Swartz RP, Roecklein J Natural killer cell-mediated lysis ofMycobacterium-avium complex-infected monocytes. Journal of Clinical Immunology 1990, 10: 71–77.
Harshan KV, Gangadharam PR In vivo depletion of natural killer cell activity leads to enhanced multiplication ofMycobacterium avium complex in mice. Infection and Immunology 1991, 59: 2818–2821.
Crowle AJ, Cohn DL, Poche P Defects in sera from acquired immunodeficiency syndrome (AIDS) patients and from non-AIDS patients withMycobacterium avium infection which decrease macrophage resistance toM. avium. Infection and Immunology 1989, 57: 1445–1451.
Iseman MD Mycobacterium avium complex and the normal host: the other side of the coin. New England Journal of Medicine 1989, 321: 896–898.
Chin DP, Hopewell PC, Yajko DM, Vittinghoff E, Horsburgh CR, Hadley WK, Stone EN, Nassos PS, Ostroff SM, Jacobson MA, et al Mycobacterium avium complex in the respiratory or gastrointestinal tract and the risk ofM avium complex bacteremia in patients with human immunodeficiency virus infection. Journal of Infectious Diseases 1994, 169: 289–295.
Gillin JS, Urmacher C, West R, Shike M DisseminatedMycobacterium avium-intracellulare infection in acquired immunodeficiency syndrome mimicking Whipple's disease. Gastroenterology 1983, 85: 1187–1191.
Bermudez LE, Petrofsky M, Kolonoski P, Young LS An animal model ofMycobacterium avium complex disseminated infection after colonization of the intestinal tract. Journal of Infectious Diseases 1992, 165: 75–79.
Contreras MA, Cheung OT, Sanders DE, Goldstein RS Pulmonary infection with nontuberculous mycobacteria. American Review of Respiratory Diseases 1988, 137: 149–152.
Christensen EE, Dietz GW, Ahn CH, Chapman JS, Murry RC, Anderson J, Hurst GA Initial roentgenographic manifestations of pulmonaryMycobacterium tuberculosis, M kansasii, andM. intracellularis infections. Chest 1981, 80: 132–136.
Teirstein AS, Damsker B, Kirschner PA, Krellenstein DJ, Robinson B, Chuang MT Pulmonary infection withMycobacterium avium-intracellulare: diagnosis, clinical patterns, treatment. Mount Sinai Journal of Medicine 1990, 57: 209–215.
Wallace RJ, O'Brien R, Glassroth J, Raleigh J, Dutt A Diagnosis and treatment of disease caused by non-tuberculous mycobacteria. American Review of Respiratory Diseases 1990, 142: 940–953.
Lai KK, Stottmeier KD, Sherman IH, McCabe WR Mycobacterial cervical lymphadenopathy. Relation of etiologic agents to age. Journal of the American Medical Association 1984, 251: 1286–1288.
Horsburgh CRJ, Mason UG, Farhi DC, Iseman MD Disseminated infection withMycobacterium avium-intracellulare. A report of 13 cases and a review of the literature. Medicine 1985, 64: 36–48.
Stone AB, Schelonka RL, Drehner DM, McMahon DP, Ascher DP DisseminatedMycobacterium avium complex in non-human immunodeficiency virus-infected pediatric patients. Pediatric Infectious Disease Journal 1992, 11: 960–964.
Nightingale SD, Byrd LT, Southern PM, Jockusch JD, Cal SX, Wynne BA Incidence ofMycobacterium avium-intracellulare complex bacteremia in human immunodeficiency virus-positive patients. Journal of Infectious Diseases 1992, 165: 1082–1085.
Wong B, Edwards FF, Kiehn TE, Whimbey E, Donnelly H, Bernard EM, Gold JW, Armstrong D Continuous high-gradeMycobacterium avium-intracellulare bacteremia in patients with the acquired immune deficiency syndrome. American Journal of Medicine 1985, 78: 35–40.
Heifets LB Dilemmas and realities in drug susceptibility testing ofM. avium-M, intracellulare and other slowly growing nontuberculous mycobacteria. In: Heifets LB (ed): Drug susceptibility in the chemotherapy of mycobacterial infections. CRC Press, Boca Raton, 1991, p. 124–146.
Heifets LB, Iseman MD Choice of antimicrobial agents forM. avium disease based on quantitative tests of drug susceptibility. New England Journal of Medicine 1990, 323: 419–420.
Heifets LB MIC as a quantitative measurement of the susceptibility ofMycobacterium avium strains to seven antituberculosis drugs. Antimicrobial Agents and Chemotherapy 1988, 32: 1131–1136.
Heifets LB, Lindholm-Levy PJ, Comstock RD Clarithromycin minimal inhibitory and bactericidal concentrations againstMycobacterium avium. American Review of Respiratory Diseases 1992, 145: 856–858.
Horsburgh CRJ, Mason UG, Heifets LB, Southwick K, Labrecque J, Iseman MD Response to therapy of pulmonaryMycobacterium avium-intracellulare infection correlates with results of in vitro susceptibility testing. American Review of Respiratory Diseases 1987, 135: 418–421.
Gordon SM, Horsburgh CR Jr, Peloquin CA, Havlik JA, Metchock B, Heifets LB, McGowan JE, Thompson SE Low serum levels of oral antimycobacterial agents in patients with disseminatedMycobacterium avium complex disease. Journal of Infectious Diseases 1993, 168: 1559–1562.
Yajko DM, Nassos PS, Sanders CA, Gonzalez PC, Hadley WK Comparison of the intracellular activities of clarithromycin and erythromycin againstMycobacterium avium complex strains in J774 cells and in alveolar macrophages from human immunodeficiency virus type 1-infected individuals. Antimicrobial Agents and Chemotherapy 1992, 36: 1163–1165.
Gangadharam PR, Edwards CK, Murthy PS, Pratt PF An acute infection model forMycobacterium intracellulare disease using beige mice: preliminary results. American Review of Respiratory Diseases 1983, 127: 648–649.
Brown ST, Edwards FF, Bernard EM, Niki Y, Armstrong D Progressive disseminated infection withMycobacterium avium complex after intravenous and oral challenge in cyclosporine-treated rats. Journal of Infectious Diseases 1991, 164: 922–977.
Ellner JJ, Goldberger MJ, Parenti DM Mycobacterium avium infection and AIDS: a therapeutic dilemma in rapid evolution. Journal of Infectious Diseases 1991, 163: 1326–1335.
Bermudez LE, Young LS Activities of amikacin, roxithromycin, and azithromycin alone or in combination with tumor necrosis factor againstMycobacterium avium complex. Antimicrobial Agents and Chemotherapy 1988, 32: 1149–1153.
Perronne C, Gikas A, Truffot-Pernot C, Grosset J, Vilde JL, Pocidalo JJ Activities of sparfloxacin, azithromycin, temafloxacin, and rifapentine compared with that of clarithromycin against multiplication ofMycobacterium avium complex within human macrophages. Antimicrobial Agents and Chemotherapy 1991, 35: 1356–1359.
Cynamon MH, Klemens SP Activity of azithromycin againstMycobacterium avium infection in beige mice. Antimicrobial Agents and Chemotherapy 1992, 36: 1611–1613.
Fernandes PB, Hardy DJ, McDaniel D, Hanson CW, Swanson RN In vitro and in vivo activities of clarithromycin againstMycobacterium avium. Antimicrobial Agents and Chemotherapy 1989, 33: 1531–1534.
Ji B, Lounis N, Truffot-Pernot C, Grosset J Selection of resistant mutants ofMycobacterium avium in beige mice by clarithromycin monotherapy. Antimicrobial Agents and Chemotherapy 1992, 36: 2839–2840.
O'Brien RJ, Lyle MA, Snider DEJ Rifabutin (ansamycin LM 427): a new rifamycin-S derivative for the treatment of mycobacterial diseases. Reviews in Infectious Diseases 1987, 9: 519–530.
Nightingale SD, Cameron DW, Gordin FM, Sullam PM, Cohn DL, Chaisson RE, Eron LJ, Sparti PD, Bihari B, Kaufman DL, et al Two controlled trials of rifabutin prophylaxis againstMycobacterium avium complex infection in AIDS. New England Journal of Medicine 1993, 329 (12): 828–833.
Leysen DC, Haemers A, Pattyn SR Mycobacteria and the new quinolones. Antimicrobial Agents and Chemotherapy 1989, 33: 1–5.
Heifets LB, Lindholm LP MICs and MBCs of Win 57273 againstMycobacterium avium andM. tuberculosis. Antimicrobial Agents and Chemotherapy 1990, 34: 770–774.
Cynamon MH, Swenson CE, Palmer GS, Ginsberg RS Liposome-encapsulated-amikacin therapy ofMycobacterium avium complex infection in beige mice. Antimicrobial Agents and Chemotherapy 1989, 33: 1179–1183.
Etzkorn ET, Aldarondo S, McAllister CK, Matthews J, Ognibene AJ Medical therapy ofMycobacterium avium-intracellulare pulmonary disease. American Review of Respiratory Diseases 1986, 134: 442–445.
Davidson PT, Khanijo V, Goble M, Moulding TS Treatment of disease due toMycobacterium intracellulare. Reviews in Infectious Diseases 1981, 3: 1052–1059.
Reich JM, Johnson RE Mycobacterium avium complex pulmonary disease. Incidence, presentation, and response to therapy in a community setting. American Review of Respiratory Diseases 1991, 143: 1381–1385.
Moran JF;Alexander LG, Staub EW, Young WGJ, Sealy WC Long-term results of pulmonary resection for atypical mycobacterial disease. Annals of Thoracic Surgery 1983, 35: 597–604.
Horsburgh CRJ, Havlik JA, Ellis DA, Kennedy E, Fann SA, Dubois RE, Thompson SE Survival of patients with acquired immune deficiency syndrome and disseminatedMycobacterium avium complex infection with and without antimycobacterial chemotherapy. American Review of Respiratory Diseases 1991, 144: 557–559.
Jacobson MA, Yajko D, Northfelt D, Charlebois E, Gary D, Brosgart C, Sanders CA, Hadley WK Randomized, placebo-controlled trial of rifampin, ethambutol, and ciprofloxacin for AIDS patients with disseminatedMycobacterium avium complex infections. Journal of Infectious Diseases 1993, 168: 112–119.
Hoy J, Mijch A, Sandland M, Grayson L, Lucas R, Dwyer B Quadruple-drug therapy forMycobacterium avium-intracellulare bacteremia in AIDS patients. Journal of Infectious Diseases 1990, 161: 801–805.
Chiu J, Nussbaum J, Bozzette S, Tilles JG, Young LS, Leedom J, Heseltine PN, McCutchan JA Treatment of disseminatedMycobacterium avium complex infection in AIDS with amikacin, ethambutol, rifampin, and ciprofloxacin. Annals of Internal Medicine 1990, 113: 358–361.
Kemper CA, Meng TC, Nussbaum J, Chiu J, Feigal DF, Bartok AE, Leedom JM, Tilles JG, Deresinski SC, McCutchan JA Treatment ofMycobacterium avium complex bacteremia in AIDS with a four-drug oral regimen. Rifampin, ethambutol, clofazimine, and ciprofloxacin. Annals of Internal Medicine 1992, 116: 466–472.
de Lalla F, Maserati R, Scarpellini P, Marone P, Nicolin R, Caccamo F, Rigoli R Clarithromycin-ciprofloxacinamikacin for therapy ofMycobacterium avium-Mycobacterium intracellulare bacteremia in patients with AIDS. Antimicrobial Agents and Chemotherapy 1992, 36: 1567–1569.
Young LS, Wiviott L, Wu M, Kolonoski P, Bolan R, Inderlied CB Azithromycin for treatment ofMycobacterium avium-intracellulare complex infection in patients with AIDS. Lancet 1991, 338: 1107–1109.
Dautzenberg B, Saint Marc T, Meyohas MC Clarithromycin and other antimicrobial agents in the treatment of disseminatedMycobacterium avium infections in patients with acquired immunodeficiency syndrome. Archives of Internal Medicine 1993, 153: 368–372.
Narang PK, Trapnell CB, Schoenfelder JR, Lavelle JP, Bianchine JR Fluconazole and enhanced effect of rifabutin prophylaxis. New England Journal of Medicine 1994, 330: 1316–1317.
Masur H Recommendations on prophylaxis and therapy for disseminatedMycobacterium avium complex disease in patients infected with the human immunodeficiency virus. New England Journal of Medicine 1993, 329: 898–904.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Havlir, D.V. Mycobacterium avium complex: Advances in therapy. Eur. J. Clin. Microbiol. Infect. Dis. 13, 915–924 (1994). https://doi.org/10.1007/BF02111492
Issue Date:
DOI: https://doi.org/10.1007/BF02111492