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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

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dc.contributor.author Alcántara, Roberto
dc.contributor.author Fuentes, Patricia
dc.contributor.author Antiparra, Ricardo
dc.contributor.author Santos, Marco
dc.contributor.author Gilman, Robert H.
dc.contributor.author Kirwan, Daniela E.
dc.contributor.author Zimic, Mirko
dc.contributor.author Sheen, Patricia
dc.date.accessioned 2018-11-30T17:17:15Z
dc.date.available 2018-11-30T17:17:15Z
dc.date.issued 2018
dc.identifier.uri https://hdl.handle.net/20.500.12866/4120
dc.description.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 to determine PZA resistance: MODS-Wayne. 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 addition of 10% ferrous ammonium sulfate. Using a PZA concentration of 800 µg/mL, sensitivity and specificity were evaluated at three time different periods of incubation (Reading 1, reading 2, reading 3)) using a composite 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, agreement of 95.3% and kappa index of 0.86 compared to MGIT-PZA, and 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. en_US
dc.language.iso eng
dc.publisher American Society for Microbiology
dc.relation.ispartof urn:issn:1098-660X
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject ammonium sulfate en_US
dc.subject antibiotic resistance en_US
dc.subject antibiotic sensitivity en_US
dc.subject Article en_US
dc.subject colorimetry en_US
dc.subject concentration (parameter) en_US
dc.subject controlled study en_US
dc.subject drug hydrolysis en_US
dc.subject incubation time en_US
dc.subject intermethod comparison en_US
dc.subject isoniazid en_US
dc.subject microscopy en_US
dc.subject MODS en_US
dc.subject Mycobacterium tuberculosis en_US
dc.subject nonhuman en_US
dc.subject priority journal en_US
dc.subject pyrazinamide en_US
dc.subject Pyrazinamide en_US
dc.subject pyrazinoic acid en_US
dc.subject Pyrazinoic acid en_US
dc.subject rifampicin en_US
dc.subject sensitivity and specificity en_US
dc.subject sequence analysis en_US
dc.subject Sputum en_US
dc.subject sputum analysis en_US
dc.subject sputum culture en_US
dc.subject standard en_US
dc.subject supernatant en_US
dc.subject Tuberculosis en_US
dc.title MODS-Wayne, a colorimetric adaptation of the Microscopic-Observation Drug Susceptibility (MODS) assay for detection of mycobacterium tuberculosis pyrazinamide resistance from sputum samples en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1128/JCM.01162-18
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.02.00 es_PE
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#1.06.01


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