Affiliation:
1. Center for Infectious Diseases Research and Experimental Therapeutics (CIDRET), Baylor Research Institute, Dallas, Texas, USA
2. Department of Public Health and Community Medicine, Universidad ICESI, Cali, Colombia
3. Department of Medicine, University of Cape Town, Observatory, Cape Town, South Africa
Abstract
ABSTRACT
In 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.
Funder
Baylor Research Institute
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
98 articles.
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