Author:
Perumal Rubeshan,Bionghi Neda,Nimmo Camus,Letsoalo Marothi,Cummings Matthew J.,Hopson Madeleine,Wolf Allison,Jubaer Shamim Al,Padayatchi Nesri,Naidoo Kogieleum,Larsen Michelle H.,O’Donnell Max
Abstract
AbstractRationaleBedaquiline is a novel antimycobacterial agent for drug-resistant tuberculosis (DR-TB) and is classified as a World Health Organization (WHO) Group A drug due to its excellent clinical efficacy, high bactericidal activity, and potent sterilizing effect. Baseline and treatment-emergent bedaquiline resistance have been described but prevalence and incidence have not been reported, leading to gaps in the knowledge required to design strategies to optimize MDR-TB clinical outcomes and prevent the amplification of bedaquiline resistance.MethodsWe performed a systematic review and meta-analysis to estimate the frequency of, and mutations associated with, baseline and acquired (treatment-emergent) bedaquiline resistance in clinicalMtbisolates. Pooled estimates of bedaquiline resistance were generated by proportional meta-analysis in R version 4.2.2 using dmetar, metafor and meta packages. Resistance associated variants associated with prevalent and incident bedaquiline resistance were identified.ResultsData from 14 studies were included; 14 and 9 studies reported on pre-treatment and acquired bedaquiline resistance, respectively. The pooled prevalence of pre-treatment bedaquiline resistance was 2.4% (95% CI 1.7 – 3.5), with significant heterogeneity across all studies (I266%, p<0.01). The pooled prevalence of treatment-emergent bedaquiline resistance was 2.1% (95% CI 1.4 - 3.0), with no significant heterogeneity across the included studies (I20%, p=0.97).DiscussionWe found a concerning frequency of bedaquiline resistance present at baseline and acquired during treatment. Urgent strategies are required to mitigate further resistance to this crucial drug.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
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