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Drug susceptibility testing and mortality in patients treated for tuberculosis in high-burden countries: a multicentre cohort study

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dc.contributor.author Zürcher, K.
dc.contributor.author Ballif, M.
dc.contributor.author Fenner, L.
dc.contributor.author Borrell, S.
dc.contributor.author Keller, P.M.
dc.contributor.author Gnokoro, J.
dc.contributor.author Marcy, O.
dc.contributor.author Yotebieng, M.
dc.contributor.author Diero, L.
dc.contributor.author Carter, E.J.
dc.contributor.author Rockwood, N.
dc.contributor.author Wilkinson, R.J.
dc.contributor.author Cox, H.
dc.contributor.author Ezati, N.
dc.contributor.author Abimiku, A.G.
dc.contributor.author Collantes, J.
dc.contributor.author Avihingsanon, A.
dc.contributor.author Kawkitinarong, K.
dc.contributor.author Reinhard, M.
dc.contributor.author Hömke, R.
dc.contributor.author Huebner, R.
dc.contributor.author Gagneux, S.
dc.contributor.author Böttger, E.C.
dc.contributor.author Egger, M.
dc.contributor.author Chammartin, F.
dc.contributor.author Boettger, E.C.
dc.contributor.author Keller, P.
dc.contributor.author Abimiku, A.
dc.contributor.author Wenzi, L.
dc.contributor.author Tabala, M.
dc.contributor.author Warren, R.
dc.contributor.author Streicher, E.
dc.contributor.author Wilkinson, R.J.
dc.contributor.author Carter, E.J.
dc.contributor.author Zamudio Fuertes, Carlos Eduardo
dc.contributor.author Sohn, A.
dc.contributor.author Petersen, T.
dc.contributor.author Kasipong, N.
dc.contributor.author N'Guessan, K.
dc.contributor.author International epidemiology Databases to Evaluate AIDS
dc.date.accessioned 2019-07-04T16:59:29Z
dc.date.available 2019-07-04T16:59:29Z
dc.date.issued 2019
dc.identifier.uri https://hdl.handle.net/20.500.12866/6771
dc.description.abstract Background: Drug resistance is a challenge for the global control of tuberculosis. We examined mortality in patients with tuberculosis from high-burden countries, according to concordance or discordance of results from drug susceptibility testing done locally and in a reference laboratory. Methods: This multicentre cohort study was done in Côte d'Ivoire, Democratic Republic of the Congo, Kenya, Nigeria, South Africa, Peru, and Thailand. We collected Mycobacterium tuberculosis isolates and clinical data from adult patients aged 16 years or older. Patients were stratified by HIV status and tuberculosis drug resistance. Molecular or phenotypic drug susceptibility testing was done locally and at the Swiss National Center for Mycobacteria, Zurich, Switzerland. We examined mortality during treatment according to drug susceptibility test results and treatment adequacy in multivariable logistic regression models adjusting for sex, age, sputum microscopy, and HIV status. Findings: We obtained M tuberculosis isolates from 871 patients diagnosed between 2013 and 2016. After exclusion of 237 patients, 634 patients with tuberculosis were included in this analysis; the median age was 33·2 years (IQR 26·9–42·5), 239 (38%) were women, 272 (43%) were HIV-positive, and 69 (11%) patients died. Based on the reference laboratory drug susceptibility test, 394 (62%) strains were pan-susceptible, 45 (7%) monoresistant, 163 (26%) multidrug-resistant (MDR), and 30 (5%) had pre-extensively or extensively drug resistant (pre-XDR or XDR) tuberculosis. Results of reference and local laboratories were concordant for 513 (81%) of 634 patients and discordant for 121 (19%) of 634. Overall, sensitivity to detect any resistance was 90·8% (95% CI 86·5–94·2) and specificity 84·3% (80·3–87·7). Mortality ranged from 6% (20 of 336) in patients with pan-susceptible tuberculosis treated according to WHO guidelines to 57% (eight of 14) in patients with resistant strains who were under-treated. In logistic regression models, compared with concordant drug susceptibility test results, the adjusted odds ratio of death was 7·33 (95% CI 2·70–19·95) for patients with discordant results potentially leading to under-treatment. Interpretation: Inaccurate drug susceptibility testing by comparison with a reference standard leads to under-treatment of drug-resistant tuberculosis and increased mortality. Rapid molecular drug susceptibility test of first-line and second-line drugs at diagnosis is required to improve outcomes in patients with MDR tuberculosis and pre-XDR or XDR tuberculosis. en_US
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartofseries Lancet. Infectious Diseases
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject adult en_US
dc.subject amikacin en_US
dc.subject antibiotic agent en_US
dc.subject antibiotic resistance en_US
dc.subject antibiotic sensitivity en_US
dc.subject Article en_US
dc.subject bacterial strain en_US
dc.subject bacterium isolate en_US
dc.subject capreomycin en_US
dc.subject cohort analysis en_US
dc.subject controlled study en_US
dc.subject Democratic Republic Congo en_US
dc.subject ethambutol en_US
dc.subject female en_US
dc.subject human en_US
dc.subject isoniazid en_US
dc.subject kanamycin en_US
dc.subject Kenya en_US
dc.subject major clinical study en_US
dc.subject male en_US
dc.subject mortality en_US
dc.subject moxifloxacin en_US
dc.subject Mycobacterium tuberculosis en_US
dc.subject Nigeria en_US
dc.subject nonhuman en_US
dc.subject Peru en_US
dc.subject priority journal en_US
dc.subject pyrazinamide en_US
dc.subject rifampicin en_US
dc.subject South Africa en_US
dc.subject sputum cytodiagnosis en_US
dc.subject streptomycin en_US
dc.subject Thailand en_US
dc.subject tuberculosis en_US
dc.title Drug susceptibility testing and mortality in patients treated for tuberculosis in high-burden countries: a multicentre cohort study en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1016/S1473-3099(18)30673-X
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.03.08
dc.relation.issn 1474-4457

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