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dc.contributor.authorMetcalfe, John
dc.contributor.authorBacchetti, Peter
dc.contributor.authorEsmail, Ali
dc.contributor.authorReckers, Andrew
dc.contributor.authorAguilar, David
dc.contributor.authorWen, Anita
dc.contributor.authorHuo, Shu
dc.contributor.authorMuyindike, Winnie R.
dc.contributor.authorHahn, Judith A.
dc.contributor.authorDheda, Keertan
dc.contributor.authorGandhi, Monica
dc.contributor.authorGerona, Roy
dc.date.accessioned2023-02-13T08:47:25Z
dc.date.available2023-02-13T08:47:25Z
dc.date.issued2021
dc.identifier.citationMetcalfe, J., Bacchetti, P., Esmail, A., Reckers, A., Aguilar, D., Wen, A., ... & Gerona, R. (2021). Diagnostic accuracy of a liquid chromatography-tandem mass spectrometry assay in small hair samples for rifampin-resistant tuberculosis drug concentrations in a routine care setting. BMC infectious diseases, 21, 1-6.en_US
dc.identifier.urihttp://ir.must.ac.ug/xmlui/handle/123456789/2767
dc.description.abstractBackground: Treatment monitoring of drug-resistant tuberculosis (DR-TB) in resource-limited settings is challenging. We developed a multi-analyte assay for eleven anti-TB drugs in small hair samples as an objective metric of drug exposure. Methods: Small hair samples were collected from participants at various timepoints during directly observed RR-TB treatment at an inpatient tertiary referral facility in South Africa (DR-TB cohort). We assessed qualitative determination (i.e., detection above limit of detection) of bedaquiline, linezolid, clofazimine, pretomanid, levofloxacin, moxifloxacin, pyrazinamide, isoniazid, ethambutol, ethionamide, and prothionamide in an LC-MS/MS index panel assay against a reference standard of inpatient treatment records. Because treatment regimens prior to hospitalization was not available, we also analyzed specificity (for all drugs except isoniazid) using an external cohort of HIV-positive patients treated for latent TB infection with daily isoniazid (HIV/LTBI cohort) in Uganda. Results: Among the 57 DR-TB patients (58% with pre-XDR/XDR-TB; 70% HIV-positive) contributing analyzable hair samples, the sensitivity of the investigational assay was 94% or higher for all drugs except ethionamide (58.5, 95% confidence interval [CI], 40.7–99.9). Assay specificity was low across all tested analytes within the DR-TB cohort; conversely, assay specificity was 100% for all drugs in the HIV/LTBI cohort. Conclusions: Hair drug concentrations reflect long-term exposure, and multiple successive regimens commonly employed in DR-TB treatment may result in apparent false-positive qualitative and falsely elevated quantitative hair drug levels when prior treatment histories within the hair growth window are not knownen_US
dc.description.sponsorshipNIH/NIAID R01 AI123024 (P.I. Metcalfe, Gandhi) and NIH/NIAAA U01020776 (P.I. Hahn).en_US
dc.language.isoen_USen_US
dc.publisherBMC infectious diseasesen_US
dc.subjectLC-MS/MSen_US
dc.subjectHairen_US
dc.subjectMultidrug-resistant tuberculosisen_US
dc.titleDiagnostic accuracy of a liquid chromatography-tandem mass spectrometry assay in small hair samples for rifampin-resistant tuberculosis drug concentrations in a routine care settingen_US
dc.typeArticleen_US


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