dc.contributor.author | Metcalfe, John | |
dc.contributor.author | Bacchetti, Peter | |
dc.contributor.author | Esmail, Ali | |
dc.contributor.author | Reckers, Andrew | |
dc.contributor.author | Aguilar, David | |
dc.contributor.author | Wen, Anita | |
dc.contributor.author | Huo, Shu | |
dc.contributor.author | Muyindike, Winnie R. | |
dc.contributor.author | Hahn, Judith A. | |
dc.contributor.author | Dheda, Keertan | |
dc.contributor.author | Gandhi, Monica | |
dc.contributor.author | Gerona, Roy | |
dc.date.accessioned | 2023-02-13T08:36:46Z | |
dc.date.available | 2023-02-13T08:36:46Z | |
dc.date.issued | 2021 | |
dc.identifier.citation | Metcalfe, J., Bacchetti, P., Esmail, A., Reckers, A., Aguilar, D., Wen, A., ... & Gerona, R. (2021). Diagnostic Accuracy of a Liquid Chromatography-Tandem Mass Spectrometry Assay for Rifampin-resistant Tuberculosis Drug Concentrations in a Routine Care Setting. | en_US |
dc.identifier.uri | http://ir.must.ac.ug/xmlui/handle/123456789/2766 | |
dc.description.abstract | Background: 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 were 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 known. | en_US |
dc.description.sponsorship | NIH/NIAID R01 AI123024 (P.I. Metcalfe, Gandhi) and NIH/NIAAA U01020776
(P.I. Hahn). | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | Research square | en_US |
dc.subject | LC-MS/MS | en_US |
dc.subject | Hair | en_US |
dc.subject | Multidrug-resistant tuberculosis | en_US |
dc.title | Diagnostic Accuracy of a Liquid Chromatography-Tandem Mass Spectrometry Assay for Rifampin-resistant Tuberculosis Drug Concentrations in a Routine Care Setting | en_US |
dc.type | Article | en_US |