Background: Mycobacterium avium complex (MAC) infection, requiring prolonged treatment with an antibiotic combination, is an emerging public health concern.
Methods: This meta-analysis compared the efficacy of 2-drug regimens with that of 3-drug regimens in bacteriological responses, acquired macrolide resistance (AMR), and mortality among adult patients with disseminated MAC infection (DMAC) and MAC pulmonary disease (MAC-PD).
Results: Seven randomized controlled trials (RCTs) and 3 non-RCT studies, encompassing 1369 patients, were included. Treating DMAC with 2-drug regimens was associated with comparable bacteriological responses (odds ratio (OR) = 0.76, 95 % confidence interval (CI) = 0.48-1.18, P = .22) and mortality (OR = 1.29, 95 % CI = 0.59-2.83, P = .52), but had a higher risk of AMR (OR = 2.99, 95 % CI = 1.10-8.13, P = .03). For MAC-PD, 2-drug regimens were noninferior to 3-drug regimens in bacteriological responses (OR = 0.82, 95 % CI = 0.53-1.25, P = .35) and AMR (risk differences (RD) = 0.01, -0.02 to 0.05, P = .39), with no observed mortalities. Although not statistically significant compared to the 3-drug regimen, the macrolide-rifamycin regimen resulted in attenuated bacteriological responses (OR = 0.51, 95 % CI = 0.14-1.90, P = .32). However, the proportion of patients with bacteriological response (OR = 1.54, 95 % CI = 0.78-2.93, P = .23) and AMR risk (RD = 0.01, -0.02 to 0.04, P = .50) was not different between those under the macrolide-ethambutol regimen and those under 3-drug regimens.
Conclusions: The macrolide-ethambutol 2-drug regimen may be a viable alternative option for treating MAC-PD, whereas DMAC can be preferably managed with a 3-drug regimen.
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From Médecins Sans Frontières (L.G., F.V.), Sorbonne Université, INSERM Unité 1135, Centre d'Immunologie et des Maladies Infectieuses (L.G.), Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Universitaire Sorbonne Université, Hôpital Pitié-Salpêtrière, Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux (L.G.), and Epicentre (M.G., E. Baudin), Paris, and Translational Research on HIV and Endemic and Emerging Infectious Diseases, Montpellier Université de Montpellier, Montpellier, Institut de Recherche pour le Développement, Montpellier, INSERM, Montpellier (M.B.) - all in France; Interactive Development and Research, Singapore (U.K.); McGill University, Epidemiology, Biostatistics, and Occupational Health, Montreal (U.K.); UCSF Center for Tuberculosis (G.E.V., P.N., P.P.J.P.) and the Division of HIV, Infectious Diseases, and Global Medicine (G.E.V.), University of California at San Francisco, San Francisco; the National Scientific Center of Phthisiopulmonology (A.A., E. Berikova) and the Center of Phthisiopulmonology of Almaty Health Department (A.K.), Almaty, and the City Center of Phthisiopulmonology, Astana (Z.D.) - all in Kazakhstan; Médecins Sans Frontières (C.B., I.M.), the Medical Research Council Clinical Trials Unit at University College London (I.M.), and St. George's University of London Institute for Infection and Immunity (S.W.) - all in London; MedStar Health Research Institute, Washington, DC (M.C.); Médecins Sans Frontières, Mumbai (V. Chavan), the Indian Council of Medical Research Headquarters-New Delhi, New Delhi (S. Panda), and the Indian Council of Medical Research-National AIDS Research Institute, Pune (S. Patil) - all in India; the Centre for Infectious Disease Epidemiology and Research (V. Cox) and the Department of Medicine (H. McIlleron), University of Cape Town, and the Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine (S.W.) - both in Cape Town, South Africa; the Institute of Tropical Medicine, Antwerp, Belgium (B. C. J.); Médecins Sans Frontières, Geneva (G.F., N.L.); Médecins Sans Frontières, Yerevan, Armenia (O.K.); the National Center for Tuberculosis and Lung Diseases, Tbilisi, Georgia (N.K.); Partners In Health (M.K.) and Jhpiego Lesotho (L.O.) - both in Maseru; Socios En Salud Sucursal Peru (L.L., S.M.-T., J.R., E.S.-G., D.E.V.-V.), Hospital Nacional Sergio E. Bernales, Centro de Investigacion en Enfermedades Neumologicas (E.S.-G.), Hospital Nacional Dos de Mayo (E.T.), Universidad Nacional Mayor de San Marcos (E.T.), and Hospital Nacional Hipólito Unanue (D.E.V.-V.) - all in Lima; Global Health and Social Medicine, Harvard Medical School (L.L., K.J.S., M.L.R., C.D.M.), Partners In Health (L.L., K.J.S., M.L.R., C.D.M.), the Division of Global Health Equity, Brigham and Women's Hospital (K.J.S., M.L.R., C.D.M.), the Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, (L.T.), and Harvard T.H. Chan School of Public Health (L.T.) - all in Boston; and the Indus Hospital and Health Network, Karachi, Pakistan (H. Mushtaque, N.S.).
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