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MODS-Wayne, a Colorimetric Adaptation of the Microscopic-Observation Drug Susceptibility (MODS) Assay for Detection of Mycobacterium tuberculosis Pyrazinamide Resistance from Sputum Samples.

Alcántara, R; Fuentes, P; Antiparra, R; Santos, M; Gilman, RH; Kirwan, DE; Zimic, M; Sheen, P (2019) MODS-Wayne, a Colorimetric Adaptation of the Microscopic-Observation Drug Susceptibility (MODS) Assay for Detection of Mycobacterium tuberculosis Pyrazinamide Resistance from Sputum Samples. J Clin Microbiol, 57 (2). ISSN 1098-660X https://doi.org/10.1128/JCM.01162-18
SGUL Authors: Kirwan, Daniela Elisa

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Abstract

Although pyrazinamide (PZA) is a key component of first- and second-line tuberculosis treatment regimens, there is no gold standard to determine PZA resistance. Approximately 50% of multidrug-resistant tuberculosis (MDR-TB) and over 90% of extensively drug-resistant tuberculosis (XDR-TB) strains are also PZA resistant. pncA sequencing is the endorsed test to evaluate PZA susceptibility. However, molecular methods have limitations for their wide application. In this study, we standardized and evaluated a new method, MODS-Wayne, to determine PZA resistance. MODS-Wayne is based on the detection of pyrazinoic acid, the hydrolysis product of PZA, directly in the supernatant of sputum cultures by detecting a color change following the addition of 10% ferrous ammonium sulfate. Using a PZA concentration of 800 µg/ml, sensitivity and specificity were evaluated at three different periods of incubation (reading 1, reading 2, and reading 3) using a composite reference standard (MGIT-PZA, pncA sequencing, and the classic Wayne test). MODS-Wayne was able to detect PZA resistance, with a sensitivity and specificity of 92.7% and 99.3%, respectively, at reading 3. MODS-Wayne had an agreement of 93.8% and a kappa index of 0.79 compared to the classic Wayne test, an agreement of 95.3% and kappa index of 0.86 compared to MGIT-PZA, and an agreement of 96.9% and kappa index of 0.90 compared to pncA sequencing. In conclusion, MODS-Wayne is a simple, fast, accurate, and inexpensive approach to detect PZA resistance, making this an attractive assay especially for low-resource countries, where TB is a major public health problem.

Item Type: Article
Additional Information: Copyright © 2019 Alcántara et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/).
Keywords: MODS, pyrazinamide, pyrazinoic acid, sputum, tuberculosis, 06 Biological Sciences, 07 Agricultural And Veterinary Sciences, 11 Medical And Health Sciences, Microbiology
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: J Clin Microbiol
ISSN: 1098-660X
Language: eng
Dates:
DateEvent
February 2019Published
30 January 2019Published Online
27 October 2018Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
099805/Z/12/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
0687-01-10Grand Challenge CanadaUNSPECIFIED
037-2014FONDECyT-PeruUNSPECIFIED
PubMed ID: 30429257
Go to PubMed abstract
URI: http://sgultest.da.ulcc.ac.uk/id/eprint/110748
Publisher's version: https://doi.org/10.1128/JCM.01162-18

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