Epidemiological cut-off values for a 96-well broth microdilution plate for high-throughput research antibiotic susceptibility testing of M. tuberculosis
Year: 2022
Type: article
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 n ecessary 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 99 th 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.
Source: European Respiratory Journal
Authors: Philip W Fowler, Ivan Barilar, Simone Battaglia, Emanuele Borroni, Angela Pires Brandao, Alice Brankin, Andrea Maurizio Cabibbe, Joshua Carter, Daniela Maria Cirillo, Pauline Claxton, David A Clifton, Ted Cohen, Jorge Coronel, Derrick W Crook, Viola Dreyer, Sarah G Earle, Vincent Escuyer, Lucilaine Ferrazoli, George Fu Gao, Jennifer Gardy, Saheer Gharbia, Kelen Teixeira Ghisi, Arash Ghodousi, Ana Luíza Gibertoni Cruz, Louis Grandjean, Clara Grazian, Ramona Groenheit, Jennifer L Guthrie, Wencong He, Harald Hoffmann, Sarah J Hoosdally, Martin Hunt, Zamin Iqbal, Nazir Ahmed Ismail, Lisa Jarrett, Lavania Joseph, Ruwen Jou, Priti Kambli, Rukhsar Khot, Jeff Knaggs, Anastasia Koch, Donna Kohlerschmidt, Samaneh Kouchaki, Alexander S Lachapelle, Ajit Lalvani, Simon Grandjean Lapierre, Ian F Laurenson, Brice Letcher, Wan-Hsuan Lin, Chunfa Liu, Dongxin Liu, Kerri M Malone, Ayan Mandal, Mikael Mansjö, Daniela Matias, Graeme Meintjes, Flávia de Freitas Mendes, Matthias Merker, Marina Mihalic, James Millard, Paolo Miotto, Nerges Mistry, David Moore, Kimberlee A Musser, Dumisani Ngcamu, Hoang Ngoc Nhung, Stefan Niemann, Kayzad Soli Nilgiriwala, Camus Nimmo, Nana Okozi, Rosangela Siqueira Oliveira, Shaheed Vally Omar, Nicholas Paton, Timothy EA Peto, Juliana Maira Watanabe Pinhata, Sara Plesnik, Zully M Puyen, Marie Sylvianne Rabodoarivelo, Niaina Rakotosamimanana, Paola MV Rancoita, Priti Rathod, Esther Robinson, Gillian Rodger, Camilla Rodrigues, Timothy C Rodwell, Aysha Roohi, David Santos-Lazaro, Sanchi Shah, Thomas Andreas Kohl, Grace Smith, Walter Solano, Andrea Spitaleri, Philip Supply, Utkarsha Surve, Sabira Tahseen, Nguyen Thuy Thuong Thuong, Guy Thwaites, Katharina Todt, Alberto Trovato, Christian Utpatel, Annelies Van Rie, Srinivasan Vijay, Timothy M Walker, A Sarah Walker, Robin Warren, Jim Werngren, Maria Wijkander, Robert J Wilkinson, Daniel J Wilson, Penelope Wintringer, Yu-Xin Xiao, Yang Yang, Zhao Yanlin, Shen-Yuan Yao, Baoli Zhu
Institutions: University of Oxford, Research Center Borstel - Leibniz Lung Center, Instituto Adolfo Lutz, Fundação Oswaldo Cruz, Stanford Medicine, Stanford University, Yale University, Universidad Peruana Cayetano Heredia, New York State Department of Health, Wadsworth Center, Chinese Center For Disease Control and Prevention, Gates Foundation, UK Health Security Agency, Vita-Salute San Raffaele University, University College London, UNSW Sydney, Public Health Agency of Sweden, University of British Columbia, Public Health Ontario, European Bioinformatics Institute, National Institute for Communicable Diseases, Public Health England, Taiwan Centers for Disease Control, P. D. Hinduja Hospital and Medical Research Centre, University of Cape Town, University of Surrey, Imperial College London, Université de Montréal, Foundation for Medical Research, Africa Health Research Institute, London School of Hygiene & Tropical Medicine, National University of Singapore, Instituto Nacional de Salud, Institut Pasteur de Madagascar, FIND, University of California San Diego, Centre National de la Recherche Scientifique, Inserm, Université de Lille, Institut Pasteur de Lille, Centre Hospitalier Universitaire de Lille, Center for Infection and Immunity of Lille, Oxford University Clinical Research Unit, University of Antwerp, University of Edinburgh, Stellenbosch University, Wellcome Centre for Infectious Diseases Research in Africa
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funders: United States Agency for International Development, Bill and Melinda Gates Foundation, Association of Public Health Laboratories, Deutsches Zentrum für Infektionsforschung, Wellcome Trust, Francis Crick Institute, Newton Fund, Robertson Foundation, UK Research and Innovation, National Institute for Health Research Health Protection Research Unit, Cancer Research UK, National Institute for Health and Care Research, Department of Health and Social Care, Royal Society, Imperial College London, University of Oxford, European Commission, Great Ormond Street Hospital Charity, National Research Foundation, South African Medical Research Council, Public Health Agency, Fundação de Amparo à Pesquisa do Estado de São Paulo, National Natural Science Foundation of China, Public Health England, Chinese Academy of Sciences, Fonds Wetenschappelijk Onderzoek, Universiteit Stellenbosch, Universiteit Antwerpen, Folkhälsomyndigheten, Vlaamse regering, National Science and Technology Major Project, National Institutes of Health, Centers for Disease Control and Prevention, University of California, San Diego, Medical Research Council, Leibniz-Gemeinschaft, Institute of Microbiology, Chinese Academy of Sciences, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases
Awards: Performance of methods for diagnosis of multidrug-resistant tuberculosis and Extensively Resistant. Applicability in a Reference Laboratory, G1080657738, Linking human genotype and immunological phenotype to understand pathogenesis and improve treatment in tuberculosis, Human Genetics and Disease Biology: Core Renewal for the Wellcome Trust Centre for Human Genetics, G1188516431, G1288721568, G1433103571, G162807682, Use of whole genome sequencing for tuberculosis diagnostics, G1782819212, Marie Curie Training Network on Particle Detectors, G1937767665, Using the Mycobacterium tuberculosis Genome to Predict Tuberculosis Pathology, Drug Resistance Acquisition and Identify Community Transmission Sites, G2006052962, Health Priorities in Resource-Limited Settings, G2064496343, G2153320237, Understanding within-patient Mycobacterium tuberculosis genetic diversity to prevent drug-resistance, Evaluation of novel therapeutic strategies to accelerate bacterial clearance and host recovery in disseminated HIV-associated tuberculosis, G2542180245, Defining interventions to reduce mortality in severe HIV-associated tuberculosis., University of Oxford - to improve control of tuberculosis, and facilitate the WHO’s initiative to eliminate tuberculosis by 2050, by better, faster and more targeted trea..., G284475574, G2874879453, G3054123256, G3298528487, G3309060605, G339059223, G342153202, Health Priorities in Resource-Limited Settings, Host directed therapies against tuberculosis., G3873106536, G3960360271, G3964318989, Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Development of a Centre for Whole Genome Sequencing studies of Mycobacterium., G4040994733, G4170600162, LEVERAGING CESGA TO RESEARCH CENTER OF EXCELLENCE, G434337789, G4353802202, G4400603338, G4459750365, Characterization of mutations in clinical isolates of Mycobacterium tuberculosis resistant to 1st and 2nd line drugs and the relationship between mutations and phenotypic resistance levels to isoniazid., G4758841269, NIHR Senior Investigator Award, G5117283442, Understanding within-patient Mycobacterium tuberculosis genetic diversity to prevent drug-resistance, G5301648897, Linking human genotype and immunological phenotype to understand pathogenesis and improve treatment in tuberculosis, G5319874880, G5320943612, G5356295135, G5522199286, Centre for Infectious Diseases Research in Africa (CIDRI-Africa), G5547571862, G5631954005, How do people get multi-drug resistant tuberculosis?, G5728235598, Comprehensive Resistance Prediction for Tuberculosis: an International Consortium (CRyPTIC), Evaluation of novel therapeutic strategies to accelerate bacterial clearance and host recovery in disseminated HIV-associated tuberculosis, G6010844705, Medical Scientist Training Program, G6308935749, G677189189, Comprehensive Resistance Prediction for Tuberculosis: an International Consortium (CRyPTIC), G6868616705, G6987093609, G7065286958, G7079742530, G7106164421, G7196713885, How do people get multi-drug resistant tuberculosis?, G7322909815, Human Genetics and Disease Biology: Core Renewal for the Wellcome Trust Centre for Human Genetics, G7364435899, G790109484, G8005632289, G8061781955, G8140873135, G8216014321, G8289385587, G8290657359, APHL/CDC PARTNERSHIP: STRENGTHENING PUBLIC HEALTH LABORATORIES, G8391552583, Statistical Methods for Whole Genome Phenotype Mapping in Bacterial Populations., G9000151629, G9000203537, The Genomics of Multidrug-Resistant Tuberculosis Transmission, G9000226936, G906761509
OpenAlex ID: W4221007313