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Pulmonary disease (PD) caused by Mycobacterium avium complex (MAC) is increasing worldwide. We conducted a systematic review of studies that include microbiologic outcomes to evaluate current macrolide-based treatment regimens. ⋯ To date, randomized studies on treatment outcome in patients with MAC PD are scarce. Long-term treatments with ATS-recommended regimens for patients who are macrolide susceptible are superior to other macrolide-based therapies. A standardized definition of treatment success and genotypic distinction between reinfection and relapse by means of pretreatment and posttreatment identification of MAC species in cases of microbiologic recurrences may help to optimize evaluation of treatment regimens in the future.