Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Mar 29;4(2):dlac029.
doi: 10.1093/jacamr/dlac029. eCollection 2022 Apr.

Acquired bedaquiline resistance during the treatment of drug-resistant tuberculosis: a systematic review

Jahan Saeed Mallick  1 , Parvati Nair  1 , Elizabeth Tabitha Abbew  1   2 , Armand Van Deun  3 , Tom Decroo  1
Affiliations
Review

Acquired bedaquiline resistance during the treatment of drug-resistant tuberculosis: a systematic review

Jahan Saeed Mallick et al. JAC Antimicrob Resist. .

Abstract

Background: Drug-resistant tuberculosis (DR-TB) is considered to be a public health threat and is difficult to cure, requiring a lengthy treatment with potent, potentially toxic drugs. The novel antimicrobial agent bedaquiline has shown promising results for patients with DR-TB, improving the rate of culture conversion and reducing TB-related mortality. However, increasing numbers of cases with acquired bedaquiline resistance (ABR) have been reported in recent years.

Methods: This systematic review aimed to assess the frequency of ABR and characteristics of patients acquiring it. Studies showing data on sequential bedaquiline drug-susceptibility testing in patients treated with a bedaquiline-containing regimen were included. The databases CENTRAL, PubMed and Embase were manually searched, and 866 unique records identified, eventually leading to the inclusion of 13 studies. Phenotypic ABR was assessed based on predefined MIC thresholds and genotypic ABR based on the emergence of resistance-associated variants.

Results: The median (IQR) frequency of phenotypic ABR was 2.2% (1.1%-4.6%) and 4.4% (1.8%-5.8%) for genotypic ABR. Among the studies reporting individual data of patients with ABR, the median number of likely effective drugs in a treatment regimen was five, in accordance with WHO recommendations. In regard to the utilization of important companion drugs with high and early bactericidal activity, linezolid was included in the regimen of most ABR patients, whereas the usage of other group A (fluoroquinolones) and former group B drugs (second-line injectable drugs) was rare.

Conclusions: Our findings suggest a relevant frequency of ABR, urging for a better protection against it. Therefore, treatment regimens should include drugs with high resistance-preventing capacity through high and early bactericidal activity.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
PRISMA flow chart. Chart showing the number of studies included for assessing the frequency of ABR. BDQ, bedaquiline.
See this image and copyright information in PMC

References

    1. WHO . Global Tuberculosis Report 2021. 2021. https://www.who.int/publications/i/item/9789240037021.
    1. WHO . Global Tuberculosis Report 2020. 2020. https://www.who.int/publications/i/item/9789240013131.
    1. Andrei S, Droc G, Stefan G. FDA approved antibacterial drugs: 2018-2019. Discoveries (Craiova) 2019; 7: e102. - PMC - PubMed
    1. Li Y, Sun F, Zhang W. Bedaquiline and delamanid in the treatment of multidrug-resistant tuberculosis: promising but challenging. Drug Dev Res 2019; 80: 98–105. - PMC - PubMed
    1. Nahid P, Mase SR, Migliori GBet al. Treatment of drug-resistant tuberculosis. an official ATS/CDC/ERS/IDSA clinical practice guideline. Am J Respir Crit Care Med 2019; 200: e93–142. - PMC - PubMed

LinkOut - more resources