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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Epidemiological cutoff values for a 96-well broth microdilution plate for high-throughput research antibiotic susceptibility testing of M. tuberculosis
European Respiratory Journal, Volume 60, No. 4, Year 2022
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Description
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. Copyright ©The authors 2022.
Authors & Co-Authors
Fowler, Philip William
United Kingdom, Oxford
University of Oxford
Barilar, Ivan
Germany, Borstel
Forschungszentrum Borstel - Zentrum Für Medizin Und Biowissenschaften
Battaglia, Simone
Italy, Milan
Irccs Ospedale San Raffaele
Borroni, Emanuele
Italy, Milan
Irccs Ospedale San Raffaele
Brandão, Angela Pires
Brazil, Rio de Janeiro
Fundacao Oswaldo Cruz
Brazil, Cerqueira Cesar
Instituto Adolfo Lutz
Brankin, Alice E.
United Kingdom, Oxford
University of Oxford
Cabibbe, Andrea Maurizio
Italy, Milan
Irccs Ospedale San Raffaele
Carter, Joshua James
United States, Stanford
Stanford University School of Medicine
Cirillo, D. M.
Italy, Milan
Irccs Ospedale San Raffaele
Claxton, Pauline M.
Unknown Affiliation
Clifton, David Andrew
United Kingdom, Oxford
University of Oxford
Cohen, Ted
United States, New Haven
Yale University
Coronel, Jorge E.
Peru, Lima
Universidad Peruana Cayetano Heredia
Crook, Derrick W.
United Kingdom, Oxford
University of Oxford
Dreyer, Viola
Germany, Borstel
Forschungszentrum Borstel - Zentrum Für Medizin Und Biowissenschaften
Earle, Sarah G.
United Kingdom, Oxford
University of Oxford
Escuyer, Vincent E.
United States, Albany
New York State Department of Health
Ferrazoli, Lucilaine
Brazil, Cerqueira Cesar
Instituto Adolfo Lutz
Gao, George Fu
China, Beijing
Chinese Center for Disease Control and Prevention
Gardy, Jennifer L.
Unknown Affiliation
Gharbia, Saheer E.
United Kingdom, London
Uk Health Security Agency
Ghisi, Kelen Teixeira
Brazil, Cerqueira Cesar
Instituto Adolfo Lutz
Ghodousi, Arash
Italy, Milan
Irccs Ospedale San Raffaele
Italy, Milan
Università Vita-salute San Raffaele
Cruz, Ana Lúıza Gibertoni
United Kingdom, Oxford
University of Oxford
Grandjean, Louis
United Kingdom, London
University College London
Grazian, Clara
Australia, Sydney
Unsw Sydney
Groenheit, Ramona
Sweden, Solna
Public Health Agency of Sweden
Guthrie, Jennifer L.
Canada, Vancouver
The University of British Columbia
Canada, Toronto
Public Health Ontario
He, Wencong
China, Beijing
Chinese Center for Disease Control and Prevention
Hoffmann, Harald
Unknown Affiliation
Hoosdally, Sarah Jayne
United Kingdom, Oxford
University of Oxford
Hunt, Martin
United Kingdom, Oxford
University of Oxford
United Kingdom, Hinxton
Embl’s European Bioinformatics Institute
Iqbal, Zamin
United Kingdom, Hinxton
Embl’s European Bioinformatics Institute
Ismail, Nazir Ahmed
South Africa, Johannesburg
National Institute for Communicable Diseases
Jarrett, Lisa
United Kingdom, London
Public Health England
Joseph, Lavania
South Africa, Johannesburg
National Institute for Communicable Diseases
Jou, Ruwen
Taiwan, Taipei
Taiwan Centers for Disease Control
Kambli, Priti
India, Mumbai
P.d. Hinduja National Hospital and Medical Research Centre
Khot, Rukhsar
India, Mumbai
P.d. Hinduja National Hospital and Medical Research Centre
Knaggs, Jeff
United Kingdom, Oxford
University of Oxford
United Kingdom, Hinxton
Embl’s European Bioinformatics Institute
Koch, Anastasia Sideris
South Africa, Cape Town
University of Cape Town
Kohlerschmidt, Donna J.
United States, Albany
New York State Department of Health
Kouchaki, Samaneh
United Kingdom, Oxford
University of Oxford
United Kingdom, Guildford
University of Surrey
Lachapelle, Alexander S.
United Kingdom, Oxford
University of Oxford
Lalvani, Ajit
United Kingdom, London
Imperial College London
Grandjean-Lapierre, Simon
Canada, Montreal
University of Montreal
Laurenson, Ian F.
Unknown Affiliation
Letcher, Brice
United Kingdom, Hinxton
Embl’s European Bioinformatics Institute
Lin, Wanhsuan
Taiwan, Taipei
Taiwan Centers for Disease Control
Liu, Chunfa
China, Beijing
Chinese Center for Disease Control and Prevention
Liu, Dongxin
China, Beijing
Chinese Center for Disease Control and Prevention
Malone, Kerri Marie
United Kingdom, Hinxton
Embl’s European Bioinformatics Institute
Mandal, Ayan
India, Mumbai
The Foundation for Medical Research India
Mansjö, Mikael
Sweden, Solna
Public Health Agency of Sweden
Matias, Daniela
United Kingdom, London
Public Health England
Meintjes, Graeme Ayton
South Africa, Cape Town
University of Cape Town
de Freitas Mendes, Flávia
Brazil, Cerqueira Cesar
Instituto Adolfo Lutz
Merker, Matthias
Germany, Borstel
Forschungszentrum Borstel - Zentrum Für Medizin Und Biowissenschaften
Mihalic, Marina
Unknown Affiliation
Millard, James Daniel
South Africa, Durban
Africa Health Research Institute
Miotto, Paolo
Italy, Milan
Irccs Ospedale San Raffaele
Mistry, Nerges Furdoon
India, Mumbai
The Foundation for Medical Research India
Moore, David A.J.
United Kingdom, London
London School of Hygiene & Tropical Medicine
Musser, Kimberlee Aruda
United States, Albany
New York State Department of Health
Ngcamu, Dumisani
South Africa, Johannesburg
National Institute for Communicable Diseases
Nhung, Hoang Ngoc
Viet Nam, Ho Chi Minh City
Oxford University Clinical Research Unit
Niemann, Stefan
Germany, Borstel
Forschungszentrum Borstel - Zentrum Für Medizin Und Biowissenschaften
Germany, Hamburg
German Center for Infection Research Dzif
Germany, Borstel
German Center for Infection Research Dzif
Germany, Munich
German Center for Infection Research Dzif
Nilgiriwala, Kayzad Soli
India, Mumbai
The Foundation for Medical Research India
Nimmo, Camus
United Kingdom, London
University College London
Okozi, Nana
South Africa, Johannesburg
National Institute for Communicable Diseases
de Oliveira, Rosângela Siqueira
Brazil, Cerqueira Cesar
Instituto Adolfo Lutz
Omar, Shaheed Vally
South Africa, Johannesburg
National Institute for Communicable Diseases
Paton, Nicholas Iain
Singapore, Singapore City
National University of Singapore
Peto, Timothy E.A.
United Kingdom, Oxford
University of Oxford
Pinhata, Juliana Maira Watanabe
Brazil, Cerqueira Cesar
Instituto Adolfo Lutz
Plesnik, Sara
Unknown Affiliation
Puyén, Zully M.
Peru, Lima
Instituto Nacional de Salud, Lima
Rabodoarivelo, Marie Sylvianne
Madagascar, Antananarivo
Institut Pasteur de Madagascar
Rakotosamimanana, Niaina
Madagascar, Antananarivo
Institut Pasteur de Madagascar
Rancoita, Paola M.V.
Italy, Milan
Università Vita-salute San Raffaele
Rathod, Priti
United Kingdom, London
Public Health England
Robinson, Esther R.
United Kingdom, London
Public Health England
Rodger, Gillian
United Kingdom, Oxford
University of Oxford
Rodrigues, Camilla S.
India, Mumbai
P.d. Hinduja National Hospital and Medical Research Centre
Rodwell, Timothy C.
Switzerland, Geneva
Find
United States, La Jolla
University of California, San Diego
Roohi, Aysha
United Kingdom, Oxford
University of Oxford
Santos-Lázaro, David
Peru, Lima
Instituto Nacional de Salud, Lima
Shah, Sanchi
India, Mumbai
The Foundation for Medical Research India
Kohl, Thomas Andreas
Germany, Borstel
Forschungszentrum Borstel - Zentrum Für Medizin Und Biowissenschaften
Smith, Grace E.
United Kingdom, London
Uk Health Security Agency
United Kingdom, London
Public Health England
Solano, Walter
Peru, Lima
Universidad Peruana Cayetano Heredia
Spitaleri, Andrea
Italy, Milan
Irccs Ospedale San Raffaele
Italy, Milan
Università Vita-salute San Raffaele
Supply, Philip
France, Lille
Chu Lille
Surve, Utkarsha
India, Mumbai
P.d. Hinduja National Hospital and Medical Research Centre
Tahseen, Sabira
Unknown Affiliation
Thuong, Nguyen Thuy
Viet Nam, Ho Chi Minh City
Oxford University Clinical Research Unit
Thwaites, Guy E.
United Kingdom, Oxford
University of Oxford
Viet Nam, Ho Chi Minh City
Oxford University Clinical Research Unit
Todt, Katharina
Unknown Affiliation
Trovato, A.
Italy, Milan
Irccs Ospedale San Raffaele
Utpatel, Christian
Germany, Borstel
Forschungszentrum Borstel - Zentrum Für Medizin Und Biowissenschaften
van Rie, Annelies
Belgium, Antwerpen
Universiteit Antwerpen
Walker, Timothy M.
United Kingdom, Oxford
University of Oxford
Viet Nam, Ho Chi Minh City
Oxford University Clinical Research Unit
Walker, Anne Sarah
United Kingdom, Oxford
University of Oxford
Warren, Robin Mark
South Africa, Stellenbosch
Stellenbosch University
Werngren, Jim
Sweden, Solna
Public Health Agency of Sweden
Wijkander, Maria
Sweden, Solna
Public Health Agency of Sweden
Wilkinson, Robert John
United Kingdom, London
Imperial College London
South Africa, Cape Town
Wellcome Centre for Infectious Diseases Research in Africa
United Kingdom, London
The Francis Crick Institute
Wilson, Daniel J.
United Kingdom, Oxford
University of Oxford
Wintringer, Penelope
United Kingdom, Hinxton
Embl’s European Bioinformatics Institute
Yang, Yang
United Kingdom, Oxford
University of Oxford
Zhu, Baoli
China, Beijing
Chinese Academy of Sciences
Statistics
Citations: 38
Authors: 111
Affiliations: 45
Identifiers
Doi:
10.1183/13993003.00239-2022
ISSN:
09031936
Research Areas
Genetics And Genomics
Infectious Diseases
Study Design
Cross Sectional Study
Study Approach
Qualitative