Universidad Peruana Cayetano Heredia

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

Mostrar el registro sencillo del ítem

dc.contributor.author Finci, Iris
dc.contributor.author Albertini, Audrey
dc.contributor.author Merker, Matthias
dc.contributor.author Andres, Sonke
dc.contributor.author Bablishvili, Nino
dc.contributor.author Barilar, Ivan
dc.contributor.author Cáceres Nakiche, Tatiana
dc.contributor.author Crudu, Valeriu
dc.contributor.author Gotuzzo Herencia, José Eduardo
dc.contributor.author Hapeela, Nchimunya
dc.contributor.author Hoffmann, Harald
dc.contributor.author Hoogland, Christine
dc.contributor.author Kohl, Thomas A.
dc.contributor.author Kranzer, Katharina
dc.contributor.author Mantsoki, Anna
dc.contributor.author Maurer, Florian P.
dc.contributor.author Nicol, Mark P.
dc.contributor.author Noroc, Ecaterina
dc.contributor.author Plesnik, Sara
dc.contributor.author Rodwell, Timothy
dc.contributor.author Ruhwald, Morten
dc.contributor.author Savidge, Theresa
dc.contributor.author Salfinger, Max
dc.contributor.author Streicher, Elizabeth
dc.contributor.author Tukvadze, Nestani
dc.contributor.author Warren, Robin
dc.contributor.author Zemanay, Widaad
dc.contributor.author Zurek, Anna
dc.contributor.author Niemann, Stefan
dc.contributor.author Denkinger, Claudia M.
dc.date.accessioned 2022-09-09T18:52:23Z
dc.date.available 2022-09-09T18:52:23Z
dc.date.issued 2022
dc.identifier.uri https://hdl.handle.net/20.500.12866/12158
dc.description.abstract 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). en_US
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartofseries Lancet. Microbe
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Mycobacterium tuberculosis en_US
dc.subject antimicrobial susceptibility testing en_US
dc.subject multicentre observational study en_US
dc.title Investigating resistance in clinical Mycobacterium tuberculosis complex isolates with genomic and phenotypic antimicrobial susceptibility testing: a multicentre observational study en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1016/S2666-5247(22)00116-1
dc.relation.issn 2666-5247


Ficheros en el ítem

Ficheros Tamaño Formato Ver

No hay ficheros asociados a este ítem.

Este ítem aparece en la(s) siguiente(s) colección(ones)

Mostrar el registro sencillo del ítem

info:eu-repo/semantics/restrictedAccess Excepto si se señala otra cosa, la licencia del ítem se describe como info:eu-repo/semantics/restrictedAccess

Buscar en el Repositorio


Listar

Panel de Control

Estadísticas