Bedaquiline for treatment of non-tuberculous mycobacteria (NTM): a systematic review and meta-analysis

Abstract

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.

Therapy of Mycobacterium abscessus Infections in Solid Organ Transplant Patients

“…Bedaquiline is a diarylquinolone antibiotic that inhibits mycobacterial ATP synthase and is better known for its use in multidrug-resistant Mycobacterium tuberculosis infections as recommended by the World Health Organization [ 40 , 41 ]. A systematic review and meta-analysis revealed that bedaquiline-containing regimens were effective in treating NTM extrapulmonary infection but not pulmonary infection [ 42 ]. Another report revealed potential clinical and microbiologic activity of bedaquiline in patients with MABC lung disease [ 43 ].…”

“…Bedaquiline was successfully used as part of a combination therapy in two HIV patients with disseminated NTM [ 45 ]. Note that resistance to bedaquiline has been noted [ 42 ]. Bedaquiline was largely well tolerated, and the most common adverse effects were nausea and QTc prolongation [ 42 ].…”

“…Note that resistance to bedaquiline has been noted [ 42 ]. Bedaquiline was largely well tolerated, and the most common adverse effects were nausea and QTc prolongation [ 42 ].…”

Growing from common ground: nontuberculous mycobacteria and bronchiectasis

“…Many other antimicrobial strategies remain to be further evaluated for NTM-PD (reviewed in [ 144 – 146 ]), including new formulations of existing drugs such as inhaled clofazimine [ 147 ], repurposed drugs licensed to treat multidrug-resistant tuberculosis such as bedaquiline [ 148 ], novel molecules within existing antibiotic classes such as omadacycline [ 149 ] and the newer oxazolidinone tedizolid [ 150 ], and bacteriophage therapy, which has been explored primarily in M. abscessus infections up to date [ 151 ].…”