Baseline and treatment-emergent bedaquiline resistance in drug-resistant tuberculosis: A systematic review and meta-analysis
Abstract Rationale Bedaquiline 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.Methods We 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.Results Data 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).Discussion We 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..
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
bioRxiv.org - (2024) vom: 23. Apr. Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Perumal, Rubeshan [VerfasserIn] |
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| doi: |
10.1101/2023.08.07.23293687 |
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| PPN (Katalog-ID): |
XBI040448428 |
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| 520 | |a Abstract Rationale Bedaquiline 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.Methods We 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.Results Data 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).Discussion We 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. | ||
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| 700 | 1 | |a Bionghi, Neda |e verfasserin |4 aut | |
| 700 | 1 | |a Nimmo, Camus |e verfasserin |4 aut | |
| 700 | 1 | |a Letsoalo, Marothi |e verfasserin |4 aut | |
| 700 | 1 | |a Cummings, Matthew J. |e verfasserin |4 aut | |
| 700 | 1 | |a Hopson, Madeleine |e verfasserin |4 aut | |
| 700 | 1 | |a Wolf, Allison |e verfasserin |4 aut | |
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| 700 | 1 | |a Larsen, Michelle H. |e verfasserin |4 aut | |
| 700 | 1 | |a O’Donnell, Max |e verfasserin |4 aut | |
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