Systematic review and meta-analyses of the effect of chemotherapy on pulmonary Mycobacterium abscessus outcomes and disease recurrence [PublishAheadOfPrint]

Background. In pharmacokinetic/pharmacodynamics models of pulmonary Mycobacterium abscessus complex, the recommended macrolide-containing combination therapy has poor kill rates. However, clinical outcomes are unknown.

Methods. We searched the literature for studies published between 1990-2017 that reported microbial outcomes in patients treated for pulmonary M. abscessus disease. Good outcome was defined as sustained sputum culture conversion (SSCC) without relapse. Random effects models were used to pool studies and estimate proportions of patients with good outcomes. Odds ratio (OR) and 95% confidence intervals [CI] were computed. Sensitivity analyses and meta-regression were used to assess robustness of findings.

Results. In 19 studies of 1533 patients, combination therapy was administered to 508 patients with M. abscessus subspecies abscessus (Maa), 204 with M. abscessus subspecies massiliense (Mam), and 301 with M. abscessus with no species specified. Macrolide-containing regimens achieved SSCC in only 77/233 (34%) new Maa patients versus 117/141 (54%) in Mam patients (OR=0.108 [95% CI, 0.066-0.181]). In refractory disease, SSCC was achieved in 20% (95% CI, 7-36), which was not significantly different across subspecies. The estimated recurrent rates per month were 1.835% (range 1.667%-3.196%) for Maa versus 0.683% (range 0.229%-1.136%) for Mam (OR=6.189 [95%CI, 2.896-13.650]). The proportion of patients with good outcome was 52/223 (23%) with Maa versus 118/141 (84%) with Mam disease (OR=0.059 (95% 0.034-0.101).

Conclusions. Maa pulmonary disease outcomes with the currently recommended regimens are atrocious, with outcomes similar to extensively drug-resistant tuberculosis. Therapeutically, the concept of "nontuberculous mycobacteria" is misguided. There is an urgent need to craft entirely new treatment regimens.

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