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Quantitative (1)H Nuclear Magnetic Resonance Assay for the Rapid Detection of Pyrazinamide Resistance in Mycobacterium tuberculosis from Sputum Samples.

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dc.contributor.author Lopez, Juan M.
dc.contributor.author Zimic-Peralta, Mirko Juan
dc.contributor.author Vallejos, Katherine
dc.contributor.author Sevilla, Diego
dc.contributor.author Quispe-Carbajal, Mariella
dc.contributor.author Roncal Ríos, Elisa del Rocío
dc.contributor.author Rodríguez Puma, Joseline
dc.contributor.author Rodríguez Quero, Jhojailith Yetzibith
dc.contributor.author Antiparra Villa, Ricardo Alfonso
dc.contributor.author Arteaga Pillaca, Héctor Jesús
dc.contributor.author Gilman, Robert H.
dc.contributor.author Maruenda, Helena
dc.contributor.author Sheen Cortavarria, Patricia
dc.coverage.spatial Hospital Nacional Hipólito Unánue, Lima, Perú
dc.coverage.spatial Laboratorio de Referencia Regional de Tuberculosis, Callao, Perú
dc.date.accessioned 2023-05-19T14:08:33Z
dc.date.available 2023-05-19T14:08:33Z
dc.date.issued 2023
dc.identifier.uri https://hdl.handle.net/20.500.12866/13521
dc.description.abstract Tuberculosis (TB), caused by Mycobacterium tuberculosis, is one of the 10 leading killer diseases in the world. At least one-quarter of the population has been infected, and there are 1.3 million deaths annually. The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains challenges TB treatments. One of the drugs widely used in first- and second-line regimens is pyrazinamide (PZA). Statistically, 50% of MDR and 90% of XDR clinical strains are resistant to PZA, and recent studies have shown that its use in patients with PZA-resistant strains is associated with higher mortality rates. Therefore, the is an urgent need for the development of an accurate and efficient PZA susceptibility assay. PZA crosses the M. tuberculosis membrane and is hydrolyzed to its active form, pyrazinoic acid (POA), by a nicotinamidase encoded by the pncA gene. Up to 99% of clinical PZA-resistant strains have mutations in this gene, suggesting that this is the most likely mechanism of resistance. However, not all pncA mutations confer PZA resistance, only the ones that lead to limited POA production. Therefore, susceptibility to PZA may be addressed simply by its ability to form, or not, POA. Here, we present a nuclear magnetic resonance method to accurately quantify POA directly in the supernatant of sputum cultures collected from TB patients. The ability of the clinical sputum culture to hydrolyze PZA was determined, and the results were correlated with the results of other biochemical and molecular PZA drug susceptibility assays. The excellent sensitivity and specificity values attained suggest that this method could become the new gold standard for the determination of PZA susceptibility. en_US
dc.language.iso eng
dc.publisher American Society for Microbiology
dc.relation.ispartofseries Journal of Clinical Microbiology
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject tuberculosis en_US
dc.subject pyrazinamide en_US
dc.subject drug susceptibility test en_US
dc.subject clinical trial en_US
dc.subject nuclear magnetic resonance en_US
dc.subject Mycobacterium tuberculosis en_US
dc.subject antibiotic resistance en_US
dc.subject.mesh Tuberculosis
dc.subject.mesh Pirazinamida
dc.subject.mesh Pruebas de Sensibilidad Microbiana
dc.subject.mesh Ensayo Clínico
dc.subject.mesh Espectroscopía de Resonancia Magnética
dc.subject.mesh Mycobacterium tuberculosis
dc.subject.mesh Farmacorresistencia Microbiana
dc.title Quantitative (1)H Nuclear Magnetic Resonance Assay for the Rapid Detection of Pyrazinamide Resistance in Mycobacterium tuberculosis from Sputum Samples. en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1128/jcm.01522-22
dc.relation.issn 1098-660X


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