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Second-line anti-tuberculosis drug concentrations for susceptibility testing in the MODS assay

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dc.contributor.author Fitzwater, Sean Patrick
dc.contributor.author Sechler, G. Andrew
dc.contributor.author Jave, Oswaldo
dc.contributor.author Coronel, Jorge
dc.contributor.author Mendoza, Alberto
dc.contributor.author Gilman, Robert Hugh
dc.contributor.author Friedland, Jon S.
dc.contributor.author Moore, David Alexander James
dc.date.accessioned 2022-01-04T20:29:57Z
dc.date.available 2022-01-04T20:29:57Z
dc.date.issued 2013
dc.identifier.uri https://hdl.handle.net/20.500.12866/10455
dc.description.abstract Multidrug-resistant tuberculosis (TB) threatens TB control worldwide. The microscopic observation drug susceptibility (MODS) assay is a low-cost, high-performance TB diagnostic tool for rapid liquid culture and direct isoniazid and rifampicin drug susceptibility testing (DST). The Objetive: of this study was to explore the potential for extending the MODS assay to rapid second-line DST and to identify critical concentrations of candidate drugs for prospective testing. Sputum samples from 94 TB culture-positive patients receiving second-line TB agents were cultured following standardised MODS protocols, with a range of titrations of antimicrobial drugs added. Critical concentrations were determined using a modified Kaplan–Meier survival curve analysis. Candidate critical concentrations were determined for capreomycin (10 μg·mL−1), ciprofloxacin (1.25 μg·mL−1), cycloserine (40 μg·mL−1), ethambutol (10 μg·mL−1), ethionamide (5 μg·mL−1), kanamycin (5 μg·mL−1), para-aminosalicylic acid (10 μg·mL−1) and streptomycin (10 μg·mL−1). No cut-off point was identified for the other second-line drugs or for pyrazinamide. At particular concentrations of some second-line TB drugs this novel Kaplan–Meier analysis clearly differentiated populations that were susceptible or resistant. These candidate critical concentrations should now be tested in a range of epidemiological settings to define the performance of direct, second-line TB DST with MODS, offering potential low-cost second-line TB DST capacity. en_US
dc.language.iso eng
dc.publisher European Respiratory Society
dc.relation.ispartofseries European Respiratory Journal
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Humans en_US
dc.subject Peru en_US
dc.subject tuberculosis en_US
dc.subject Phenotype en_US
dc.subject Drug Resistance, Multiple, Bacterial en_US
dc.subject multidrug resistance en_US
dc.subject Dose-Response Relationship, Drug en_US
dc.subject ROC Curve en_US
dc.subject Diagnostics en_US
dc.subject extensively drug-resistant tuberculosis en_US
dc.subject second-line drug susceptibility testing en_US
dc.subject Antitubercular Agents en_US
dc.subject Sputum en_US
dc.subject Microbial Sensitivity Tests en_US
dc.subject Tuberculosis en_US
dc.subject Multidrug-Resistant en_US
dc.title Second-line anti-tuberculosis drug concentrations for susceptibility testing in the MODS assay en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1183/09031936.00059812
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.02.07
dc.relation.issn 1399-3003


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