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Epidemiological cutoff values for a 96-well broth microdilution plate for high-throughput research antibiotic susceptibility testing of M. tuberculosis

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dc.contributor.author Fowler, P.W.
dc.contributor.author Barilar, I.
dc.contributor.author Battaglia, S.
dc.contributor.author Borroni, E.
dc.contributor.author Brandao, A.P.
dc.contributor.author Brankin, A.
dc.contributor.author Cabibbe, A.M.
dc.contributor.author Carter, J.
dc.contributor.author Cirillo, D.M.
dc.contributor.author Claxton, P.
dc.contributor.author Clifton, D.A.
dc.contributor.author Cohen, T.
dc.contributor.author Coronel, Jorge
dc.contributor.author Crook, D.W.
dc.contributor.author Dreyer, V.
dc.contributor.author Earle, S.G.
dc.contributor.author Escuyer, V.
dc.contributor.author Ferrazoli, L.
dc.contributor.author Gao, G.F.
dc.contributor.author Gardy, J.
dc.contributor.author Gharbia, S.
dc.contributor.author Ghisi, K.T.
dc.contributor.author Ghodousi, A.
dc.contributor.author Cruz, A.L.G.
dc.contributor.author Grandjean, Louis
dc.contributor.author Grazian, C.
dc.contributor.author Groenheit, R.
dc.contributor.author Guthrie, J.L.
dc.contributor.author He, W.
dc.contributor.author Hoffmann, H.
dc.contributor.author Hoosdally, S.J.
dc.contributor.author Hunt, M.
dc.contributor.author Iqbal, Z.
dc.contributor.author Ismail, N.A.
dc.contributor.author Jarrett, L.
dc.contributor.author Joseph, L.
dc.contributor.author Jou, R.
dc.contributor.author Kambli, P.
dc.contributor.author Khot, R.
dc.contributor.author Knaggs, J.
dc.contributor.author Koch, A.
dc.contributor.author Kohlerschmidt, D.
dc.contributor.author Kouchaki, S.
dc.contributor.author Lachapelle, A.S.
dc.contributor.author Lalvani, A.
dc.contributor.author Lapierre, S.G.
dc.contributor.author Laurenson, I.F.
dc.contributor.author Letcher, B.
dc.contributor.author Lin, W.-H.
dc.contributor.author Liu, C.
dc.contributor.author Liu, D.
dc.contributor.author Malone, K.M.
dc.contributor.author Mandal, A.
dc.contributor.author Mansjö, M.
dc.contributor.author Matias, D.
dc.contributor.author Meintjes, G.
dc.contributor.author de Freitas Mendes, F.
dc.contributor.author Merker, M.
dc.contributor.author Mihalic, M.
dc.contributor.author Millard, J.
dc.contributor.author Miotto, P.
dc.contributor.author Mistry, N.
dc.contributor.author Moore, David Alexander James
dc.contributor.author Musser, K.A.
dc.contributor.author Ngcamu, D.
dc.contributor.author Nhung, H.N.
dc.contributor.author Niemann, S.
dc.contributor.author Nilgiriwala, K.S.
dc.contributor.author Nimmo, C.
dc.contributor.author Okozi, N.
dc.contributor.author Oliveira, R.S.
dc.contributor.author Omar, S.V.
dc.contributor.author Paton, N.
dc.contributor.author Peto, T.E.A.
dc.contributor.author Pinhata, J.M.W.
dc.contributor.author Plesnik, S.
dc.contributor.author Puyen, Z.M.
dc.contributor.author Rabodoarivelo, M.S.
dc.contributor.author Rakotosamimanana, N.
dc.contributor.author Rancoita, P.M.V.
dc.contributor.author Rathod, P.
dc.contributor.author Robinson, E.
dc.contributor.author Rodger, G.
dc.contributor.author Rodrigues, C.
dc.contributor.author Rodwell, T.C.
dc.contributor.author Roohi, A.
dc.contributor.author Santos-Lazaro, D.
dc.contributor.author Shah, S.
dc.contributor.author Kohl, T.A.
dc.contributor.author Smith, G.
dc.contributor.author Solano, Walter
dc.contributor.author Spitaleri, A.
dc.contributor.author Supply, P.
dc.contributor.author Surve, U.
dc.contributor.author Tahseen, S.
dc.contributor.author Thuong, N.T.T.
dc.contributor.author Thwaites, G.
dc.contributor.author Todt, K.
dc.contributor.author Trovato, A.
dc.contributor.author Utpatel, C.
dc.contributor.author Van Rie, A.
dc.contributor.author Vijay, S.
dc.contributor.author Walker, T.M.
dc.contributor.author Walker, A.S.
dc.contributor.author Warren, R.
dc.contributor.author Werngren, J.
dc.contributor.author Wijkander, M.
dc.contributor.author Wilkinson, R.J.
dc.contributor.author Wilson, D.J.
dc.contributor.author Wintringer, P.
dc.contributor.author Xiao, Y.-X.
dc.contributor.author Yang, Y.
dc.contributor.author Yanlin, Z.
dc.contributor.author Yao, S.-Y.
dc.contributor.author Zhu, B.
dc.date.accessioned 2022-12-14T14:25:33Z
dc.date.available 2022-12-14T14:25:33Z
dc.date.issued 2022
dc.identifier.uri https://hdl.handle.net/20.500.12866/12878
dc.description.abstract Drug susceptibility testing of M. tuberculosis is rooted in a binary susceptible/resistant paradigm. Whilst there are considerable advantages in measuring the minimum inhibitory concentrations (MICs) of a panel of drugs for an isolate it is necessary to measure the epidemiological cutoff values (ECOFF/ECVs) to permit comparison with qualitative data. Here we present ECOFF/ECVs for 13 anti-TB compounds, including bedaquiline and delamanid, derived from 20,637 clinical isolates collected by 14 laboratories based in 11 countries on five continents. Each isolate was incubated for 14 days on a dry 96-well broth microdilution plate and then read. Resistance to most of the drugs due to prior exposure is expected and the MIC distributions for many of the compounds are complex and therefore a phenotypically wild-type population could not be defined. Since a majority of samples also underwent genetic sequencing, we defined a genotypically wild-type population and measured the MIC of the 99th percentile by direct measurement and via fitting a Gaussian using interval regression. The proposed ECOFF/ECV values were then validated by comparing to the MIC distributions of high-confidence genetic variants that confer resistance and to qualitative drug susceptibility tests obtained via Mycobacterial Growth Indicator Tube and the Microscopic-Observation Drug-Susceptibility assay. These ECOFF/ECV values will inform and encourage the more widespread adoption of broth microdilution – this is a cheap culture-based method that tests the susceptibility of 12-14 antibiotics on a single 96-well plate and so could help personalise the treatment of tuberculosis. 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 Respiratory en_US
dc.subject infections en_US
dc.subject tuberculosis en_US
dc.subject microdilution en_US
dc.subject M. tuberculosis en_US
dc.title Epidemiological cutoff values for a 96-well broth microdilution plate for high-throughput research antibiotic susceptibility testing of M. tuberculosis en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1183/13993003.00239-2022
dc.relation.issn 1399-3003


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