review · Journal of Antimicrobial Chemotherapy
Non-tuberculous mycobacteria infections are rising in incidence and associated mortality, presenting significant therapeutic challenges because of natural antibiotic resistance. A systematic assessment of fifty studies evaluated the performance of bedaquiline against these pathogens across laboratory experiments, animal models, and human patients. In animal studies, bedaquiline treatment reduced bacterial loads by 1.86 times compared to no treatment within thirty days. Clinical evidence indicates that regimens containing bedaquiline successfully treated extrapulmonary non-tuberculous mycobacterial infections in humans, although they proved ineffective for pulmonary infections. An epidemiological cut-off value of 0.5 milligrams per millilitre was established solely for Mycobacterium abscessus due to limited available data. Although bedaquiline demonstrates potent antibacterial action against multiple species, evidence on genetic mutations linked to resistance remains scarce, highlighting the necessity for additional research to guide clinical regimens.
Non-tuberculous mycobacteria naturally resist many common antibiotics, leading to rising infection rates and increased mortality. Evaluating existing drugs like bedaquiline provides critical insight into alternative therapies. Demonstrating efficacy in extrapulmonary infections gives clinicians clearer guidance on when the drug may succeed, while identifying where it fails helps avoid ineffective treatments and directs future clinical investigations.
The evidence supports repositioning bedaquiline, an existing antimicrobial, specifically for treating extrapulmonary non-tuberculous mycobacteria infections. Target users include clinicians, hospital infectious disease departments, and treatment guideline developers. In terms of readiness, the therapy is already tested in humans for certain presentations, but further clinical studies and resistance profiling are required before expanded, standardised clinical use can occur.
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BACKGROUND: Non-tuberculous mycobacteria (NTM) infections are increasing in incidence and associated mortality. NTM are naturally resistant to a variety of antibiotics, complicating treatment. We conducted a literature assessment on the efficacy of bedaquiline in treating NTM species in vitro and in vivo (animal models and humans); meta-analyses were performed where possible. METHOD: Four databases were searched using specific terms. Publications were included according to predefined criteria. Bedaquiline's impact on NTM in vitro, MICs and epidemiological cut-off (ECOFF) values were evaluated. A meta-analysis of bedaquiline efficacy against NTM infections in animal models was performed. Culture conversion, cure and/or relapse-free cure were used to evaluate the efficacy of bedaquiline in treating NTM infection in humans. RESULTS: Fifty studies met the inclusion criteria: 33 assessed bedaquiline's impact on NTM in vitro, 9 in animal models and 8 in humans. Three studies assessed bedaquiline's efficacy both in vitro and in vivo. Due to data paucity, an ECOFF value of 0.5 mg/mL was estimated for Mycobacterium abscessus only. Meta-analysis of animal studies showed a 1.86× reduction in bacterial load in bedaquiline-treated versus no treatment within 30 days. In humans, bedaquiline-including regimens were effective in treating NTM extrapulmonary infection but not pulmonary infection. CONCLUSIONS: Bedaquiline demonstrated strong antibacterial activity against various NTM species and is a promising drug to treat NTM infections. However, data on the genomic mutations associated with bedaquiline resistance were scarce, preventing statistical analyses for most mutations and NTM species. Further studies are urgently needed to better inform treatment strategies.
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DOI: 10.1093/jac/dkad372
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