Accès ouvert déclaré 2022 article

Investigating resistance in clinical Mycobacterium tuberculosis complex isolates with genomic and phenotypic antimicrobial susceptibility testing: a multicentre observational study

Iris Finci, Audrey Albertini, Matthias Merker, Sönke Andres, Nino Bablishvili, Ivan Barilar, Tatiana Cáceres, Valeriu Crudu, Eduardo Gotuzzo, Nchimunya Hapeela, Harald Hoffmann, Christine Hoogland, Thomas Andreas Kohl, Katharina Kranzer, Anna Mantsoki, Florian P. Maurer, Mark Patrick Nicol, Ecaterina Noroc, Sara Plesnik, Timothy C. Rodwell, Morten Rühwald, Theresa Savidge, Max Salfinger, Elizabeth Maria Streicher, Nestani Tukvadze, Robin M. Warren, Widaad Zemanay, Anna K. Zurek, Stefan Niemann, Claudia Maria Denkinger

51Citations signalées, ce qui n’est pas une note de qualité

27Institutions déclarées

12Pays d’affiliation déclarés

Rattachement africain : de, ch, ge, pe, py, md, Afrique du Sud, cz, gb, Zimbabwe, au, us. Niveau de preuve : code pays fourni par la source.

Le résumé fourni par la source

BACKGROUND: Whole-genome sequencing (WGS) of Mycobacterium tuberculosis complex has become an important tool in diagnosis and management of drug-resistant tuberculosis. However, data correlating resistance genotype with quantitative phenotypic antimicrobial susceptibility testing (AST) are scarce. METHODS: In a prospective multicentre observational study, 900 clinical M tuberculosis complex isolates were collected from adults with drug-resistant tuberculosis in five high-endemic tuberculosis settings around the world (Georgia, Moldova, Peru, South Africa, and Viet Nam) between Dec 5, 2014, and Dec 12, 2017. Minimum inhibitory concentrations (MICs) and resulting binary phenotypic AST results for up to nine antituberculosis drugs were determined and correlated with resistance-conferring mutations identified by WGS. FINDINGS: Considering WHO-endorsed critical concentrations as reference, WGS had high accuracy for prediction of resistance to isoniazid (sensitivity 98·8% [95% CI 98·5-99·0]; specificity 96·6% [95% CI 95·2-97·9]), levofloxacin (sensitivity 94·8% [93·3-97·6]; specificity 97·1% [96·7-97·6]), kanamycin (sensitivity 96·1% [95·4-96·8]; specificity 95·0% [94·4-95·7]), amikacin (sensitivity 97·2% [96·4-98·1]; specificity 98·6% [98·3-98·9]), and capreomycin (sensitivity 93·1% [90·0-96·3]; specificity 98·3% [98·0-98·7]). For rifampicin, pyrazinamide, and ethambutol, the specificity of resistance prediction was suboptimal (64·0% [61·0-67·1], 83·8% [81·0-86·5], and 40·1% [37·4-42·9], respectively). Specificity for rifampicin increased to 83·9% when borderline mutations with MICs overlapping with the critical concentration were excluded. Consequently, we highlighted mutations in M tuberculosis complex isolates that are often falsely identified as susceptible by phenotypic AST, and we identified potential novel resistance-conferring mutations. INTERPRETATION: The combined analysis of mutations and quantitative phenotypes shows the potential of WGS to produce a refined interpretation of resistance, which is needed for individualised therapy, and eventually could allow differential drug dosing. However, variability of MIC data for some M tuberculosis complex isolates carrying identical mutations also reveals limitations of our understanding of the genotype and phenotype relationships (eg, including epistasis and strain genetic background). FUNDING: Bill & Melinda Gates Foundation, German Centre for Infection Research, German Research Foundation, Excellence Cluster Precision Medicine of Inflammation (EXC 2167), and Leibniz ScienceCampus EvoLUNG.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.

Le contrôle bibliographique ouvert

DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.

Titre Crossref: Investigating resistance in clinical Mycobacterium tuberculosis complex isolates with genomic and phenotypic antimicrobial susceptibility testing: a multicentre observational study
Date Crossref: 01/09/2022
Éditeur: Elsevier BV
Type: journal-article

Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.

Où se fait cette recherche

Research Center Borstel - Leibniz Lung Center Molecular and Experimental Mycobacteriology pays non établi dans la notice
Structure de recherche
FIND pays non établi dans la notice
Organisation à but non lucratif
National Center for Tuberculosis and Lung Disease pays non établi dans la notice
Organisation à but non lucratif
Universidad Peruana Cayetano Heredia pays non établi dans la notice
Université ou école supérieure
Instituto de Medicina Tropical pays non établi dans la notice
Établissement de santé
Instituto de Medicina Tropical Alexander von Humboldt pays non établi dans la notice
Structure de recherche
Phthisiopneumology Institute "Chiril Draganiuc" pays non établi dans la notice
Établissement de santé
University of Cape Town Institute of Infectious Disease and Molecular Medicine University of Cape Town, Afrique du Sud (code pays fourni par la source)
Université ou école supérieure
Institute of Infectious Disease and Molecular Medicine Afrique du Sud (code pays fourni par la source)
Université ou école supérieure
Synlab Czech (Czechia) pays non établi dans la notice
Entreprise
Synlab (Germany) pays non établi dans la notice
Entreprise
London School of Hygiene & Tropical Medicine Research Center Borstel Harare, Zimbabwe (pays nommé en fin d’affiliation)
Université ou école supérieure

Molecular and Experimental Mycobacteriology — Research Center Borstel - Leibniz Lung Center, FIND et National Center for Tuberculosis and Lung Disease, avec 9 autres affiliations. Pays d’affiliation : Afrique du Sud, Zimbabwe.

Une affiliation ne permet pas de déduire la nationalité d’un auteur.

Les sujets associés

Tuberculosis Research and EpidemiologyMycobacterium research and diagnosisInfectious Diseases and Tuberculosis

Lire en accès ouvert Consulter la publication primaire Ouvrir le DOI