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. 2022 Mar 16;60(3):e0236221.
doi: 10.1128/jcm.02362-21. Epub 2022 Mar 16.

Whole-Genome Sequencing Has the Potential To Improve Treatment for Rifampicin-Resistant Tuberculosis in High-Burden Settings: a Retrospective Cohort Study

Helen Cox  1   2 , Galo A Goig  3   4 , Zubeida Salaam-Dreyer  1 , Anzaan Dippenaar  5 , Anja Reuter  6 , Erika Mohr-Holland  6 , Johnny Daniels  6 , Patrick G T Cudahy  7 , Mark P Nicol  8 , Sonia Borrell  3   4 , Miriam Reinhard  3   4 , Anna Doetsch  3   4 , Christian Beisel  4   9 , Sebastien Gagneux  3   4 , Robin M Warren  10 , Jennifer Furin  11
Affiliations

Whole-Genome Sequencing Has the Potential To Improve Treatment for Rifampicin-Resistant Tuberculosis in High-Burden Settings: a Retrospective Cohort Study

Helen Cox et al. J Clin Microbiol. .

Abstract

Treatment of multidrug-resistant or rifampicin-resistant tuberculosis (MDR/RR-TB), although improved in recent years with shorter, more tolerable regimens, remains largely standardized and based on limited drug susceptibility testing (DST). More individualized treatment with expanded DST access is likely to improve patient outcomes. To assess the potential of TB drug resistance prediction based on whole-genome sequencing (WGS) to provide more effective treatment regimens, we applied current South African treatment recommendations to a retrospective cohort of MDR/RR-TB patients from Khayelitsha, Cape Town. Routine DST and clinical data were used to retrospectively categorize patients into a recommended regimen, either a standardized short regimen or a longer individualized regimen. Potential regimen changes were then described with the addition of WGS-derived DST. WGS data were available for 1274 MDR/RR-TB patient treatment episodes across 2008 to 2017. Among 834 patients initially eligible for the shorter regimen, 385 (46%) may have benefited from reduced drug dosage or removing ineffective drugs when WGS data were considered. A further 187 (22%) patients may have benefited from more effective adjusted regimens. Among 440 patients initially eligible for a longer individualized regimen, 153 (35%) could have been switched to the short regimen. Overall, 305 (24%) patients had MDR/RR-TB with second-line TB drug resistance, where the availability of WGS-derived DST would have allowed more effective treatment individualization. These data suggest considerable benefits could accrue from routine access to WGS-derived resistance prediction. Advances in culture-free sequencing and expansion of the reference resistance mutation catalogue will increase the utility of WGS resistance prediction.

Keywords: Mycobacterium tuberculosis; drug resistance; treatment; tuberculosis; whole-genome sequencing.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

FIG 1
FIG 1
Changes to treatment based on drug resistance profile (combined routine and WGS DST data) for patients who would have been started on the standardized short regimen.
FIG 2
FIG 2
Changes to treatment based on drug resistance profile (combined routine and WGS DST data) for patients who would have been treated with a longer individualized regimen.
See this image and copyright information in PMC

References

    1. Furin J, Cox H, Pai M. 2019. Tuberculosis. Lancet 393:1642–1656. doi: 10.1016/S0140-6736(19)30308-3. - DOI - PubMed
    1. Zumla AI, Gillespie SH, Hoelscher M, Philips PP, Cole ST, Abubakar I, McHugh TD, Schito M, Maeurer M, Nunn AJ. 2014. New antituberculosis drugs, regimens, and adjunct therapies: needs, advances, and future prospects. Lancet Infect Dis 14:327–340. doi: 10.1016/S1473-3099(13)70328-1. - DOI - PubMed
    1. World Health Organization. 2020. WHO consolidated guidelines on tuberculosis—module 4: treatment/drug-resistant tuberculosis treatment. World Health Organization, Geneva, Switzerland. - PubMed
    1. DR-TB STAT Task Force. 2021. DR-TB Stat: global snapshot. https://drtb-stat.org/global-snapshot/. Accessed 21 August 2021.
    1. Medecins Sans Frontieres and Stop TB Partnership. 2020. Step up for TB 2020: tuberculosis policies in 37 countries.

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