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
. 2018 Oct 18;14(10):e1007297.
doi: 10.1371/journal.ppat.1007297. eCollection 2018 Oct.

Pathogen-based precision medicine for drug-resistant tuberculosis

Matthias I Gröschel  1   2 , Timothy M Walker  3 , Tjip S van der Werf  2 , Christoph Lange  4   5   6   7 , Stefan Niemann  1   7 , Matthias Merker  1
Affiliations

Pathogen-based precision medicine for drug-resistant tuberculosis

Matthias I Gröschel et al. PLoS Pathog. .
No abstract available

PubMed Disclaimer

Conflict of interest statement

Dr. Lange reports personal fees from Chiesi, Gilead, Becton Dickinson, Janssen, Lucane, Novartis, and Thermofisher, outside the submitted work.

Figures

Fig 1
Fig 1. Principle of pathogen-tailored individualized treatment design.
(A) Mutations are obtained from a whole-genome sequencing reference mapping approach that can be also transferred into a cgMLST for molecular outbreak surveillance. (B) Individual mutations are further interpreted towards their biological phenotype employing a validated consensus mutation catalogue. (C) When canonical and/or high-level resistance-conferring mutations are present, this drug should not be used. However, mutations associated with a moderate or intermediate resistance level may allow the use of drugs at increased doses. Moreover, mutations can be used to predict different treatment outcomes. Thus, by also considering phylogenetic benign mutations that do not confer resistance, a comprehensive molecular drug susceptibility profile could be inferred for a pathogen-tailored individualized treatment regimen in the future. cgMLST,core genome multilocus sequencing type; TB, tuberculosis.
See this image and copyright information in PMC

References

    1. Rigouts L, Coeck N, Gumusboga M, de Rijk WB, Aung KJ, Hossain MA, et al. Specific gyrA gene mutations predict poor treatment outcome in MDR-TB. J Antimicrob Chemother. 2016;71: 314–323. 10.1093/jac/dkv360 - DOI - PMC - PubMed
    1. Farhat MR, Jacobson KR, Franke MF, Kaur D, Murray M, Mitnick CD. Fluoroquinolone Resistance Mutation Detection Is Equivalent to Culture-Based Drug Sensitivity Testing for Predicting Multidrug-Resistant Tuberculosis Treatment Outcome: A Retrospective Cohort Study. Clin Infect Dis. 2017;65: 1364–1370. 10.1093/cid/cix556 - DOI - PMC - PubMed
    1. Hu Y, Zheng X, Ning Z, Li Q, Zhang Z, Hoffner S. Impact of genotypic and phenotypic resistance to second-line anti-tuberculosis drugs on treatment outcomes in multidrug-resistant tuberculosis in China. Int J Mycobacteriol. 2016;5 Suppl 1: S34–S35. 10.1016/j.ijmyco.2016.11.007 - DOI - PubMed
    1. Huyen MN, Cobelens FG, Buu TN, Lan NT, Dung NH, Kremer K, et al. Epidemiology of isoniazid resistance mutations and their effect on tuberculosis treatment outcomes. Antimicrob Agents Chemother. 2013;57: 3620–3627. 10.1128/AAC.00077-13 - DOI - PMC - PubMed
    1. National Research Council. Toward precision medicine: building a knowledge network for biomedical research and a new taxonomy of disease. Washington, D.C.: National Academies Press; 2011. - PubMed

Publication types

MeSH terms

Substances