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 (I2 > 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 12 months 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 low-quality studies. Nevertheless, these studies showed poor sputum conversion rates in patients receiving recommended treatment regimens.
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 (I2 > 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 12 months 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 low-quality studies. Nevertheless, these studies showed poor sputum conversion rates in patients receiving recommended treatment regimens.
Authors: Charles L Daley; Jonathan M Iaccarino; Christoph Lange; Emmanuelle Cambau; Richard J Wallace; Claire Andrejak; Erik C Böttger; Jan Brozek; David E Griffith; Lorenzo Guglielmetti; Gwen A Huitt; Shandra L Knight; Philip Leitman; Theodore K Marras; Kenneth N Olivier; Miguel Santin; Jason E Stout; Enrico Tortoli; Jakko van Ingen; Dirk Wagner; Kevin L Winthrop Journal: Eur Respir J Date: 2020-07-07 Impact factor: 16.671
Authors: Charles L Daley; Jonathan M Iaccarino; Christoph Lange; Emmanuelle Cambau; Richard J Wallace; Claire Andrejak; Erik C Böttger; Jan Brozek; David E Griffith; Lorenzo Guglielmetti; Gwen A Huitt; Shandra L Knight; Philip Leitman; Theodore K Marras; Kenneth N Olivier; Miguel Santin; Jason E Stout; Enrico Tortoli; Jakko van Ingen; Dirk Wagner; Kevin L Winthrop Journal: Clin Infect Dis Date: 2020-08-14 Impact factor: 9.079