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

Philip W. Fowler; Ivan Barilar; Simone Battaglia; Emanuele Borroni; Angela Pires Brandao; Alice Brankin; Andrea Maurizio Cabibbe; Joshua James 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 Fú Gāo; Saheer Gharbia; Jennifer Gardy; Kelen Teixeira Ghisi; Arash Ghodousi; Ana Gibertoni Cruz; Louis Grandjean; Clara Grazian; Ramona Groenheit; Jennifer Guthrie; Wencong He; Harald Hoffmann; Sarah J Hoosdally; Martin Hunt; Zamin Iqbal; Nazir Ismail; Lisa Jarrett; Lavania Joseph; Ruwen Jou; Priti Kambli; Rukhsar Khot; Jeff Knaggs; Anastasia Koch; Donna Kohlerschmidt; Samaneh Kouchaki; Alexander Lachapelle; A Lalvani; Simon Grandjean Lapierre; Ian Laurenson; Brice Letcher; Wan-Hsuan Lin; Chunfa Liu; Dongxin Liu; Kerri Marie Malone; Ayan Mandal; Mikael Mansjö; Daniela Matias; Graeme Meintjes; Flavia 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 V. Omar; Nicholas Paton; Timothy E A Peto; Juliana Maira Watanabe Pinhata; Sara Plesnik; Zully Puyen; Marie Rabodoarivelo; Niaina Rakotosamimanana; Paola M. 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; 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; Zhao Yanlin; Shen-Yuan Yao; Baoli Zhu

doi:10.1183/13993003.00239-2022

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

Philip W. Fowler, Ivan Barilar, Simone Battaglia, Emanuele Borroni, Angela Pires Brandao, Alice Brankin, Andrea Maurizio Cabibbe, Joshua James Carter, Daniela Maria Cirillo, Pauline Claxton, …

The European respiratory journal, Vol.60(4), 2200239

01/10/2022

DOI: https://doi.org/10.1183/13993003.00239-2022

PMID: 35301246

Abstract

Life Sciences & Biomedicine

Science & Technology

Respiratory System

Drug susceptibility testing of M. tuberculosis is rooted in a binary susceptible/resistant paradigm. While 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 cut-off values (ECOFF/ECVs) to permit comparison with qualitative data. Here we present ECOFF/ECVs for 13 anti-tuberculosis 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/ECVs were then validated by comparing with the MIC distributions of high-confidence genetic variants that confer resistance and with qualitative drug susceptibility tests obtained via the Mycobacterial Growth Indicator Tube (MGIT) system or Microscopic-Observation Drug Susceptibility (MODS) assay. These ECOFF/ECVs 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.

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Title: Epidemiological cutoff values for a 96-well broth microdilution plate for high-throughput research antibiotic susceptibility testing of M. tuberculosis
Creators: Philip W. Fowler - Univ Oxford, Oxford, England
Ivan Barilar - Res Ctr Borstel, Borstel, Germany
Simone Battaglia - IRCCS San Raffaele Sci Inst, Milan, Italy
Emanuele Borroni - IRCCS San Raffaele Sci Inst, Milan, Italy
Angela Pires Brandao - Fundacao Oswaldo Cruz, Rio De Janeiro, Brazil
Alice Brankin - Univ Oxford, Oxford, England
Andrea Maurizio Cabibbe
Joshua James Carter - Stanford Univ, Sch Med, Stanford, CA 94305 USA
Daniela Maria Cirillo - IRCCS San Raffaele Sci Inst, Milan, Italy
Pauline Claxton - Scottish Mycobacteria Reference Lab, Edinburgh, Midlothian, Scotland
David A Clifton - Univ Oxford, Oxford, England
Ted Cohen - Yale Sch Publ Hlth, Yale, CT USA
Jorge Coronel - Univ Peruana Cayetano Heredia, Lima, Peru
Derrick W Crook - Univ Oxford, Oxford, England
Viola Dreyer
Sarah G. Earle - Univ Oxford, Oxford, England
Vincent Escuyer - New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA
Lucilaine Ferrazoli - Adolfo Lutz Inst, Sao Paulo, Brazil
George Fú Gāo - Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China
Saheer Gharbia - UK Hlth Secur Agcy, London, England
Jennifer Gardy - Bill & Melinda Gates Fdn, Seattle, WA USA
Kelen Teixeira Ghisi - Adolfo Lutz Inst, Sao Paulo, Brazil
Arash Ghodousi - IRCCS San Raffaele Sci Inst, Milan, Italy
Ana Gibertoni Cruz - Univ Oxford, Oxford, England
Louis Grandjean - UCL, London, England
Clara Grazian - Univ New South Wales, Sydney, NSW, Australia
Ramona Groenheit - Publ Hlth Agcy Sweden, Solna, Sweden
Jennifer Guthrie - Univ British Columbia, Vancouver, BC, Canada
Wencong He - Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China
Harald Hoffmann - SYNLAB Gauting, Munich, Germany
Sarah J Hoosdally - Univ Oxford, Oxford, England
Martin Hunt - Univ Oxford, Oxford, England
Zamin Iqbal - EMBL EBI, Hinxton, England
Nazir Ismail - Natl Inst Communicable Dis, Johannesburg, South Africa
Lisa Jarrett - Publ Hlth England, Birmingham, W Midlands, England
Lavania Joseph - Natl Inst Communicable Dis, Johannesburg, South Africa
Ruwen Jou - Taiwan Ctr Dis Control, Taipei, Taiwan
Priti Kambli - Hinduja Hosp, Mumbai, Maharashtra, India
Rukhsar Khot - Hinduja Hosp, Mumbai, Maharashtra, India
Jeff Knaggs - Univ Oxford, Oxford, England
Anastasia Koch - Univ Cape Town, Cape Town, South Africa
Donna Kohlerschmidt - New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA
Samaneh Kouchaki - University of Oxford
Alexander Lachapelle - Univ Oxford, Oxford, England
A Lalvani - Imperial Coll London, London, England
Simon Grandjean Lapierre - Univ Montreal, Montreal, PQ, Canada
Ian Laurenson - Scottish Mycobacteria Reference Lab, Edinburgh, Midlothian, Scotland
Brice Letcher - EMBL EBI, Hinxton, England
Wan-Hsuan Lin - Taiwan Ctr Dis Control, Taipei, Taiwan
Chunfa Liu - Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China
Dongxin Liu
Kerri Marie Malone - EMBL EBI, Hinxton, England
Ayan Mandal - Fdn Med Res, Mumbai, Maharashtra, India
Mikael Mansjö - Publ Hlth Agcy Sweden, Solna, Sweden
Daniela Matias - Publ Hlth England, Birmingham, W Midlands, England
Graeme Meintjes - Univ Cape Town, Cape Town, South Africa
Flavia de Freitas Mendes - Adolfo Lutz Inst, Sao Paulo, Brazil
Matthias Merker - Res Ctr Borstel, Borstel, Germany
Marina Mihalic - WHO SRL Gauting, IMLred, Inst Microbiol & Lab Med, Gauting, Germany
James Millard - Africa Hlth Res Inst, Durban, South Africa
Paolo Miotto - IRCCS San Raffaele Sci Inst, Milan, Italy
Nerges Mistry - Fdn Med Res, Mumbai, Maharashtra, India
David Moore - Univ Peruana Cayetano Heredia, Lima, Peru
Kimberlee A. Musser - New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA
Dumisani Ngcamu - Natl Inst Communicable Dis, Johannesburg, South Africa
Hoang Ngoc Nhung - Univ Oxford, Clin Res Unit, Ho Chi Minh City, Vietnam
Stefan Niemann - Res Ctr Borstel, Borstel, Germany
Kayzad Soli Nilgiriwala - Fdn Med Res, Mumbai, Maharashtra, India
Camus Nimmo - UCL, London, England
Nana Okozi
Rosangela Siqueira Oliveira - Adolfo Lutz Inst, Sao Paulo, Brazil
Shaheed V. Omar - Natl Inst Communicable Dis, Johannesburg, South Africa
Nicholas Paton - Natl Univ Singapore, Singapore, Singapore
Timothy E A Peto - Univ Oxford, Oxford, England
Juliana Maira Watanabe Pinhata - Adolfo Lutz Inst, Sao Paulo, Brazil
Sara Plesnik - WHO SRL Gauting, IMLred, Inst Microbiol & Lab Med, Gauting, Germany
Zully Puyen - Inst Nacl Salud, Lima, Peru
Marie Rabodoarivelo - Inst Pasteur Madagascar, Antananarivo, Madagascar
Niaina Rakotosamimanana - Inst Pasteur Madagascar, Antananarivo, Madagascar
Paola M. Rancoita - Univ Vita Salute San Raffaele, Milan, Italy
Priti Rathod - Publ Hlth England, Birmingham, W Midlands, England
Esther Robinson - Publ Hlth England, Birmingham, W Midlands, England
Gillian Rodger - Univ Oxford, Oxford, England
Camilla Rodrigues - Hinduja Hosp, Mumbai, Maharashtra, India
Timothy C. Rodwell - FIND, Geneva, Switzerland
Aysha Roohi - Univ Oxford, Oxford, England
David Santos-Lazaro - Inst Nacl Salud, Lima, Peru
Sanchi Shah - Fdn Med Res, Mumbai, Maharashtra, India
Thomas Andreas Kohl - Res Ctr Borstel, Borstel, Germany
Grace Smith - UK Hlth Secur Agcy, London, England
Walter Solano - Univ Peruana Cayetano Heredia, Lima, Peru
Andrea Spitaleri - IRCCS San Raffaele Sci Inst, Milan, Italy
Philip Supply - Univ Lille, CNRS, INSERM,CIIL Ctr Infect & Immun Lille, CHU Lille,Inst Pasteur Lille,U1019,UMR 9017, Lille, France
Utkarsha Surve - Hinduja Hosp, Mumbai, Maharashtra, India
Sabira Tahseen - Natl TB Reference Lab, Natl TB Control Program, Islamabad, Pakistan
Nguyen Thuy Thuong - Univ Oxford, Clin Res Unit, Ho Chi Minh City, Vietnam
Guy Thwaites - Univ Oxford, Oxford, England
Katharina Todt - WHO SRL Gauting, IMLred, Inst Microbiol & Lab Med, Gauting, Germany
Alberto Trovato - IRCCS San Raffaele Sci Inst, Milan, Italy
Christian Utpatel - Res Ctr Borstel, Borstel, Germany
Annelies Van Rie - Univ Antwerp, Antwerp, Belgium
Srinivasan Vijay - Univ Edinburgh, Edinburgh, Midlothian, Scotland
Timothy M Walker - Univ Oxford, Oxford, England
A. Sarah Walker - Univ Oxford, Oxford, England
Robin Warren - Stellenbosch Univ, Cape Town, South Africa
Jim Werngren - Publ Hlth Agcy Sweden, Solna, Sweden
Maria Wijkander - Publ Hlth Agcy Sweden, Solna, Sweden
Robert J Wilkinson - Imperial Coll London, London, England
Daniel J. Wilson - Univ Oxford, Oxford, England
Penelope Wintringer - EMBL EBI, Hinxton, England
Yu-Xin Xiao - Taiwan Ctr Dis Control, Taipei, Taiwan
Yang - Univ Oxford, Oxford, England
Zhao Yanlin - Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China
Shen-Yuan Yao - Natl Inst Communicable Dis, Johannesburg, South Africa
Baoli Zhu - Chinese Acad Sci, Inst Microbiol, Beijing, Peoples R China
Publication Details: The European respiratory journal, Vol.60(4), 2200239
Publisher: European Respiratory Soc Journals Ltd
Date published: 01/10/2022
Date accepted: 22/02/2022
Grant note: Bill and Melinda Gates Foundation OPP1133541 Newton Fund 200205/Z/15/Z Wellcome 200205/Z/15/Z
Identifiers: 99777765902346
Academic Unit: School of Computer Science and Electronic Engineering
Language: English
Resource Type: Journal article
SDG (Scopus 2023): SDG 3

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

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