Systematic Review and Meta-analyses of the Effect of Chemotherapy on Pulmonary Mycobacterium abscessus Outcomes and Disease Recurrence

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.

Clinical Efficacy and Adverse Effects of Antibiotics Used to Treat Mycobacterium abscessus Pulmonary Disease

“…Two recent meta-analyses reported disappointing treatment outcomes for M. abscessus pulmonary disease; the therapeutic efficiency rates were 54% and 45.6% for all patients, and 35% and 33.0% for patients diagnosed with pulmonary, M. abscessus subsp. abscessus infections (9, 14). Similar rates of treatment success are reported here, i.e., 45.1% for all cases of M. abscessus pulmonary disease and 33.5% for cases involving M. abscessus subsp.…”

Cross-transmission is not the source of newMycobacterium abscessusinfections in a multi-centre cohort of cystic fibrosis patients

“…The clustering of globally spread sequence types was confirmed with whole genome sequencing (WGS) and has provided greater resolution in how the various lineages are related as well as predicting possible transmission routes [8,9]. A dominant method of transmission of M. abscessus remains contested [10,11], with evidence for and against patient-to-patient transmission being the common route [8,12–14]. M. abscessus is ubiquitous in the environment with its niche hypothesised to be free-living amoeba [15,16], but due to the difficulties in isolating the organism, little has been done to track environment-to-patient acquisition.…”

GenoType NTM-DR Performance Evaluation for Identification of Mycobacterium avium Complex and Mycobacterium abscessus and Determination of Clarithromycin and Amikacin Resistance

“…differential and accurate identification of NTM species, together with drug susceptibility testing (DST), is of great interest in the clinical setting. Specifically, precise Mycobacterium avium complex (MAC) species identification and Mycobacterium abscessus subspecies identification in clinical isolates are becoming increasingly important due to different treatment outcomes and epidemiological implications (4)(5)(6)(7). However, identification of these organisms is currently limited to specialized laboratories (8).…”