Meta-analyses and the evidence base for microbial outcomes in the treatment of pulmonary Mycobacterium avium-intracellulare complex disease

Objectives: To perform a systematic review and meta-analysis of the level of funding support and the sputum culture conversion rates in pulmonary Mycobacterium avium-intracellulare complex (P-MAC) disease in adult patients without cystic fibrosis or HIV infection, treated with recommended antibiotic regimens. Methods: We performed a literature search to identify clinical trials, prospective studies and registries that reported outcomes in P-MAC patients. Studies that reported P-MAC diagnosis and treatments based on established guidelines met the inclusion criteria and were examined for bias and quality. We modified existing quality scales and came up with a 10 star quality score. Outcomes meta-analysed were sputum conversion incidence ratios (IR) and their 95% CI, weighted for study quality. Results: Twenty-one studies that examined 28 regimens, including 2534 patients in intent-to-treat analyses and 1968 in per-protocol analyses, were identified. The study quality mean +/- SD scores were 5.4 +/- 2.2 out of 10 stars. Only two (9.5%) studies received public funding. There was significant heterogeneity of microbial effect among treatment regimens (I-2>40%; P>0.001). The pooled IR for sustained sputum conversion was 0.54 (95% CI 0.45-0.63) for macrolide-containing regimens versus 0.38 (0.25-0.52) with macrolide-free regimens. Prolonging therapy duration beyond 12months was associated with an average decline in sputum conversion to 22% (95% CI 1%-44%). Conclusions: Researchers working on P-MAC therapy have received very little public funding support. As a result, the evidence base for treatment guidelines is based on studies of relatively small numbers of patients in lowquality studies. Nevertheless, these studies showed poor sputum conversion rates in patients receiving recommended treatment regimens.