Abstract
ABSTRACTIn pharmacokinetic/pharmacodynamic models of pulmonary Mycobacterium abscessus complex, the recommended macrolide-containing combination therapy has poor kill rates. However, clinical outcomes are unknown. We searched the literature for studies published between 1990 and 2017 that reported microbial outcomes in patients treated for pulmonary M. abscessus disease. A 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 ratios (OR) and 95% confidence intervals (CI) were computed. Sensitivity analyses and metaregression were used to assess the robustness of findings. In 19 studies of 1,533 patients, combination therapy was administered to 508 patients with M. abscessus subsp. abscessus, 204 with M. abscessus subsp. massiliense, and 301 with M. abscessus with no subspecies specified. Macrolide-containing regimens achieved SSCC in only 77/233 (34%) new M. abscessus subsp. abscessus patients versus 117/141 (54%) M. abscessus subsp. massiliense patients (OR, 0.108 [95% CI, 0.066 to 0.181]). In refractory disease, SSCC was achieved in 20% (95% CI, 7 to 36%) of patients, which was not significantly different across subspecies. The estimated recurrent rates per month were 1.835% (range, 1.667 to 3.196%) for M. abscessus subsp. abscessus versus 0.683% (range, 0.229 to 1.136%) for M. abscessus subsp. massiliense (OR, 6.189 [95% CI, 2.896 to 13.650]). The proportion of patients with good outcomes was 52/223 (23%) with M. abscessus subsp. abscessus versus 118/141 (84%) with M. abscessus subsp. massiliense disease (OR, 0.059 [95% CI, 0.034 to 0.101]). M. abscessus subsp. abscessus pulmonary disease outcomes with the currently recommended regimens are atrocious, with outcomes similar to those for extensively drug-resistant tuberculosis. Therapeutically, the concept of nontuberculous mycobacteria is misguided. There is an urgent need to craft entirely new treatment regimens.
Highlights
Mycobacterium abscessus complex members are rapidly growing mycobacteria associated with a wide spectrum of disease in humans, of which pulmonary disease is the most recalcitrant (1)
Of the 1,166 unique citations identified through systematic search, 27 were eligible for full review, and 19 of these were included in our analyses (Fig. 1) (4, 6, 7, 11, 12, 14–16, 19–36)
We show that outcomes in patients with presumed drug-susceptible M. abscessus subsp. abscessus are dramatically worse than those for patients with multidrug-resistant TB (MDR-TB) and similar to those for patients with XDR-TB
Summary
Mycobacterium abscessus complex members are rapidly growing mycobacteria associated with a wide spectrum of disease in humans, of which pulmonary disease is the most recalcitrant (1). Complex: nonsmoking women of European descent who are Ͼ60 years old and have no history of lung disease and younger men Ͻ40 years old with prior lung disease, such as ␣-1 antitrypsin deficiency and cystic fibrosis (6) In the latter group of patients, M. abscessus complex can be a coinfection with other mycobacteria, leading to a high rate of disease recurrence (7). Abscessus disease identified a biphasic response that was universally terminated by emergence of ADR, even at optimized doses not tolerable in patients (9, 13, 16–18) This led us to ask what the real response rates of the recommended regimen in the clinic are. We systematically reviewed the literature, rated risk of bias, and determined the proportion of patients attaining sustained sputum culture conversion (SSCC) and disease recurrence in clinical studies that examined different therapy regimens for pulmonary M. abscessus complex
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
