Combined prolonged treatment is required to treat Mycobacterium avium complex (MAC) infections. However, whether the 2-drug regimen is inferior to the 3-drug regimen is still being determined.

A systematic review and meta-analysis were conducted to compare the efficacy of the two treatments regarding bacteriology responses, mortality, and acquired macrolide resistance. Randomized controlled trials (RCT), which compared two-drug and three-drug regimens published in English before December 2022, were eligible.

Six electronic databases were searched: PubMed, Cochrane Library, EMBASE, Scopus, Google Scholar, and Global Health Library. We identified 2253 studies, but only seven RCTs encompassing 724 patients were eligible for inclusion in this meta-analysis.No significant differences between the two treatments were detected when all 7 RCT studies reported bacteriologic responses were pooled (724 patients, OR=0.83, 95%CI:0.51-1.35). Regarding macrolide resistance, six studies, including 671 patients (329 with the 2-drug regimen, 342 with the 3-drug regimen), showed no significant differences between the two treatments (RD=0.06, 95%CI: -0.01 ? 0.13). Five RCTs studies reported mortality, including 553 patients (301 with the 2-drug regimen, 252 with the 3-drug regimen). One of them had no events in both arms. Four remaining studies showed no significant differences between the 2-drug and 3-drug regimens (OR=1.06, 95%CI: 0.45 ? 2.52, p=0.89).

The findings suggest that when choosing an initial regimen for MAC infection treatment, a 2-drug regimen may be appropriate. Further RCT might be needed to confirm this result.