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1. Updating the approaches to define susceptibility and resistance to anti-tuberculosis agents: implications for diagnosis and treatment

Author

Georghiou, Sophia B, Rodwell, Timothy C, Korobitsyn, Alexei, Abbadi, Said H, Ajbani, Kanchan, Alffenaar, Jan-Willem, Alland, David, Alvarez, Nataly, Andres, Sönke, Ardizzoni, Elisa, Aubry, Alexandra, Baldan, Rossella, Ballif, Marie, Barilar, Ivan, Böttger, Erik C, Chakravorty, Soumitesh, Claxton, Pauline M, Cirillo, Daniela M, Comas, Iñaki, Coulter, Chris, Denkinger, Claudia M, Derendinger, Brigitta, Desmond, Edward P, de Steenwinkel, Jurriaan EM, Dheda, Keertan, Diacon, Andreas H, Dolinger, David L, Dooley, Kelly E, Egger, Matthias, Ehsani, Soudeh, Farhat, Maha R, Fattorini, Lanfranco, Finci, Iris, Le Ray, Laure Fournier, Furió, Victoria, Groenheit, Ramona, Gumbo, Tawanda, Heysell, Scott K, Hillemann, Doris, Hoffmann, Harald, Hsueh, Po-Ren, Hu, Yi, Huang, Hairong, Hussain, Alamdar, Ismail, Farzana, Izumi, Kiyohiko, Jagielski, Tomasz, Johnson, John L, Kambli, Priti, Kaniga, Koné, Karunaratne, GHR Eranga, Sharma, Meenu Kaushal, Keller, Peter M, Kelly, Ellis C, Kholina, Margarita, Kohli, Mikashmi, Kranzer, Katharina, Laurenson, Ian F, Limberis, Jason, Lin, S-Y Grace, Liu, Yongge, López-Gavín, Alexandre, Lyander, Anna, Machado, Diana, Martinez, Elena, Masood, Faisal, Mitarai, Satoshi, Mvelase, Nomonde R, Niemann, Stefan, Nikolayevskyy, Vladyslav, Maurer, Florian P, Merker, Matthias, Miotto, Paolo, Omar, Shaheed V, Otto-Knapp, Ralf, Palaci, Moisés, Gutiérrez, Juan José Palacios, Peacock, Sharon J, Peloquin, Charles A, Perera, Jennifer, Pierre-Audigier, Catherine, Pholwat, Suporn, Posey, James E, Prammananan, Therdsak, Rigouts, Leen, Robledo, Jaime, Rockwood, Neesha, Rodrigues, Camilla, Salfinger, Max, Schechter, Marcos C, Seifert, Marva, Sengstake, Sarah, Shinnick, Thomas, Shubladze, Natalia, Sintchenko, Vitali, Sirgel, Frederick, Somasundaram, Sulochana, Sterling, Timothy R, Spitaleri, Andrea, and Streicher, Elizabeth

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Clinical Sciences, Infectious Diseases, Biodefense, Antimicrobial Resistance, Prevention, Rare Diseases, Emerging Infectious Diseases, Tuberculosis, Clinical Research, Vaccine Related, Orphan Drug, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Infection, Good Health and Well Being, Antitubercular Agents, Drug Resistance, Bacterial, Drug Resistance, Multiple, Bacterial, Humans, Microbial Sensitivity Tests, Mycobacterium tuberculosis, Tuberculosis, Multidrug-Resistant, Antimycobacterial Susceptibility Testing Group, Medical and Health Sciences, Respiratory System, Cardiovascular medicine and haematology
Abstract

Inappropriately high breakpoints have resulted in systematic false-susceptible AST results to anti-TB drugs. MIC, PK/PD and clinical outcome data should be combined when setting breakpoints to minimise the emergence and spread of antimicrobial resistance. https://bit.ly/3i43wb6

Published
2022

2. The Global Consortium for Drug-resistant Tuberculosis Diagnostics (GCDD): design of a multi-site, head-to-head study of three rapid tests to detect extensively drug-resistant tuberculosis

Author

Hillery, Naomi, Groessl, Erik J, Trollip, Andre, Catanzaro, Donald, Jackson, Lynn, Rodwell, Timothy C, Garfein, Richard S, Lin, S-Y Grace, Eisenach, Kathleen, Ganiats, Theodore G, Park, Daniel, Valafar, Faramarz, Rodrigues, Camilla, Crudu, Valeriu, Victor, Thomas C, and Catanzaro, Antonino

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Lung, Prevention, Antimicrobial Resistance, Infectious Diseases, Clinical Trials and Supportive Activities, Clinical Research, Tuberculosis, Emerging Infectious Diseases, HIV/AIDS, Rare Diseases, 4.2 Evaluation of markers and technologies, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Infection, Good Health and Well Being, Clinical Protocols, Cost-Benefit Analysis, DNA, Bacterial, Drug Resistance, Multiple, Bacterial, Extensively Drug-Resistant Tuberculosis, Genotype, Health Care Costs, Humans, India, Microbial Sensitivity Tests, Moldova, Molecular Diagnostic Techniques, Mycobacterium tuberculosis, Phenotype, Predictive Value of Tests, Prospective Studies, Reproducibility of Results, Research Design, South Africa, Sputum, Time Factors, Time-to-Treatment, Tuberculosis, Pulmonary, drug resistance, international, multi-site, rapid diagnostic tools, tuberculosis, XDR-TB, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, General & Internal Medicine, Clinical sciences, Epidemiology, Health services and systems
Abstract

BackgroundDrug-resistant tuberculosis (DR-TB) remains a threat to global public health, owing to the complexity and delay of diagnosis and treatment. The Global Consortium for Drug-resistant Tuberculosis Diagnostics (GCDD) was formed to develop and evaluate assays designed to rapidly detect DR-TB, so that appropriate treatment might begin more quickly. This paper describes the methodology employed in a prospective cohort study for head-to-head assessment of three different rapid diagnostic tools.MethodsSubjects at risk of DR-TB were enrolled from three countries. Data were gathered from a combination of patient interviews, chart reviews, and laboratory testing from each site's reference laboratory. The primary outcome of interest was reduction in time from specimen arrival in the laboratory to results of rapid drug susceptibility tests, as compared with current standard mycobacterial growth indicator tube (MGIT) drug susceptibility tests.ResultsSuccessful implementation of the trial in diverse multinational populations is explained, in addition to challenges encountered and recommendations for future studies with similar aims or populations.ConclusionsThe GCDD study was a head-to-head study of multiple rapid diagnostic assays aimed at improving accuracy and precision of diagnostics and reducing overall time to detection of DR-TB. By conducting a large prospective study, which captured epidemiological, clinical, and biological data, we have produced a high-quality unique dataset, which will be beneficial for analyzing study aims as well as answering future DR-TB research questions. Reduction in detection time for XDR-TB would be a major public health success as it would allow for improved treatment and more successful patient outcomes. Executing successful trials is critical in assessment of these reductions in highly variable populations.Trial registrationClinicalTrials.gov NCT02170441.

Published
2014

3. Determinants of Multidrug-Resistant Tuberculosis Clusters, California, USA, 2004–2007 - Volume 16, Number 9—September 2010 - Emerging Infectious Diseases journal - CDC

Author

Metcalfe, John Z, Kim, Elizabeth Y, Lin, S-Y Grace, Cattamanchi, Adithya, Oh, Peter, Flood, Jennifer, Hopewell, Philip C, and Kato-Maeda, Midori

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Clinical Sciences, Rare Diseases, Biodefense, Clinical Research, Vaccine Related, Emerging Infectious Diseases, Prevention, Tuberculosis, Infectious Diseases, Antimicrobial Resistance, Infection, Good Health and Well Being, Adolescent, Adult, Antitubercular Agents, Bacterial Proteins, California, Catalase, Cluster Analysis, Drug Resistance, Multiple, Bacterial, Female, Genes, Bacterial, Genotype, Humans, Isoniazid, Male, Middle Aged, Molecular Epidemiology, Multivariate Analysis, Mycobacterium tuberculosis, Point Mutation, Rifampin, Tuberculosis, Multidrug-Resistant, Young Adult, Public Health and Health Services, Microbiology, Clinical sciences, Epidemiology, Health services and systems
Abstract

Laboratory and epidemiologic evidence suggests that pathogen-specific factors may affect multidrug-resistant (MDR) tuberculosis (TB) transmission and pathogenesis. To identify demographic and clinical characteristics of MDR TB case clustering and to estimate the effect of specific isoniazid resistance-conferring mutations and strain lineage on genotypic clustering, we conducted a population-based cohort study of all MDR TB cases reported in California from January 1, 2004, through December 31, 2007. Of 8,899 incident culture-positive cases for which drug susceptibility information was available, 141 (2%) were MDR. Of 123 (87%) strains with genotype data, 25 (20%) were aggregated in 8 clusters; 113 (92%) of all MDR TB cases and 21 (84%) of clustered MDR TB cases occurred among foreign-born patients. In multivariate analysis, the katG S315T mutation (odds ratio 11.2, 95% confidence interval 2.2-Yen; p = 0.004), but not strain lineage, was independently associated with case clustering.

Published
2010

4. Updating the approaches to define susceptibility and resistance to anti-tuberculosis agents: implications for diagnosis and treatment

Author

Ministerio de Ciencia e Innovación (España), European Research Council, Comas, Iñaki [0000-0001-5504-9408], Antimycobacterial Susceptibility Testing Group, Georghiou, Sophia B., Rodwell, Timothy C., Korobitsyn, Alexei, Abbadi, Said H., Ajbani, Kanchan, Alffenaar, Jan-Willem, Alland, David, Alvarez, Nataly, Andres, Sönke, Ardizzoni, Elisa, Aubry, Alexandra, Baldan, Rossella, Ballif, Marie, Barilar, Ivan, Böttger, Erik C., Chakravorty, Soumitesh, Claxton, Pauline M., Cirillo, Daniela M., Comas, Iñaki, Coulter, Chris, Denkinger, Claudia M., Derendinger, Brigitta, Desmond, Edward P., Steenwinkel, Jurriaan E. M. de, Dheda, Keertan, Diacon, Andreas H., Dolinger, David L., Dooley, Kelly E., Egger, Matthias, Ehsani, Soudeh, Farhat, Maha R., Fattorini, Lanfranco, Finci, Iris, Fournier Le Ray, Laure, Furió, Victoria, Groenheit, Ramona, Gumbo, Tawanda, Heysell, Scott K., Hillemann, Doris, Hoffmann, Harald, Hsueh, Po-Ren, Hu, Yi, Huang, Hairong, Hussain, Alamdar, Ismail, Farzana, Izumi, Kiyohiko, Jagielski, Tomasz, Johnson, John L., Kambli, Priti, Kaniga, Koné, Karunaratne, G. H. R. Eranga, Sharma, Meenu Kaushal, Keller, Peter M., Kelly, Ellis C., Kholina, Margarita, Kohli, Mikashmi, Kranzer, Katharina, Laurenson, Ian F., Limberis, Jason, Lin, S-Y. Grace, Liu, Yongge, López-Gavín, Alexandre, Lyander, Anna, Machado, Diana, Martínez, Elena, Masood, Faisal, Mitarai, Satoshi, Mvelase, Nomonde R., Niemann, Stefan, Nikolayevskyy, Vladyslav, Maurer, Florian P., Merker, Matthias, Miotto, Paolo, Omar, Shaheed V., Otto-Knapp, Ralf, Palaci, Moisés, Palacios Gutiérrez, Juan José, Peacock, Sharon J., Peloquin, Charles A., Perera, Jennifer, Pierre-Audigier, Catherine, Pholwat, Suporn, Posey, James E., Prammananan, Therdsak, Rigouts, Leen, Robledo, Jaime, Rockwood, Neesha, Rodrigues, Camilla, Salfinger, Max, Schechter, Marcos C., Seifert, Marva, Sengstake, Sarah, Shinnick, Thomas, Shubladze, Natalia, Sintchenko, Vitali, Sirgel, Frederick, Somasundaram, Sulochana, Sterling, Timothy R., Spitaleri, Andrea, Streicher, Elizabeth, Supply, Philip, Svensson, Erik, Tagliani, Elisa, Tahseen, Sabira, Takaki, Akiko, Theron, Grant, Torrea, Gabriela, Van Deun, Armand, van Ingen, Jakko, Van Rie, Annelies, van Soolingen, Dick, Vargas Jr, Roger, Venter, Amour, Veziris, Nicolas, Villellas, Cristina, Viveiros, Miguel, Warren, Robin, Wen, Shu'an, Werngren, Jim, Wilkinson, Robert J., Yang, Caie, Yılmaz, F. Ferda, Zhang, Tingting, Zimenkov, Danila, Ismail, Nazir, Köser, Claudio U., Schön, Thomas, Ministerio de Ciencia e Innovación (España), European Research Council, Comas, Iñaki [0000-0001-5504-9408], Antimycobacterial Susceptibility Testing Group, Georghiou, Sophia B., Rodwell, Timothy C., Korobitsyn, Alexei, Abbadi, Said H., Ajbani, Kanchan, Alffenaar, Jan-Willem, Alland, David, Alvarez, Nataly, Andres, Sönke, Ardizzoni, Elisa, Aubry, Alexandra, Baldan, Rossella, Ballif, Marie, Barilar, Ivan, Böttger, Erik C., Chakravorty, Soumitesh, Claxton, Pauline M., Cirillo, Daniela M., Comas, Iñaki, Coulter, Chris, Denkinger, Claudia M., Derendinger, Brigitta, Desmond, Edward P., Steenwinkel, Jurriaan E. M. de, Dheda, Keertan, Diacon, Andreas H., Dolinger, David L., Dooley, Kelly E., Egger, Matthias, Ehsani, Soudeh, Farhat, Maha R., Fattorini, Lanfranco, Finci, Iris, Fournier Le Ray, Laure, Furió, Victoria, Groenheit, Ramona, Gumbo, Tawanda, Heysell, Scott K., Hillemann, Doris, Hoffmann, Harald, Hsueh, Po-Ren, Hu, Yi, Huang, Hairong, Hussain, Alamdar, Ismail, Farzana, Izumi, Kiyohiko, Jagielski, Tomasz, Johnson, John L., Kambli, Priti, Kaniga, Koné, Karunaratne, G. H. R. Eranga, Sharma, Meenu Kaushal, Keller, Peter M., Kelly, Ellis C., Kholina, Margarita, Kohli, Mikashmi, Kranzer, Katharina, Laurenson, Ian F., Limberis, Jason, Lin, S-Y. Grace, Liu, Yongge, López-Gavín, Alexandre, Lyander, Anna, Machado, Diana, Martínez, Elena, Masood, Faisal, Mitarai, Satoshi, Mvelase, Nomonde R., Niemann, Stefan, Nikolayevskyy, Vladyslav, Maurer, Florian P., Merker, Matthias, Miotto, Paolo, Omar, Shaheed V., Otto-Knapp, Ralf, Palaci, Moisés, Palacios Gutiérrez, Juan José, Peacock, Sharon J., Peloquin, Charles A., Perera, Jennifer, Pierre-Audigier, Catherine, Pholwat, Suporn, Posey, James E., Prammananan, Therdsak, Rigouts, Leen, Robledo, Jaime, Rockwood, Neesha, Rodrigues, Camilla, Salfinger, Max, Schechter, Marcos C., Seifert, Marva, Sengstake, Sarah, Shinnick, Thomas, Shubladze, Natalia, Sintchenko, Vitali, Sirgel, Frederick, Somasundaram, Sulochana, Sterling, Timothy R., Spitaleri, Andrea, Streicher, Elizabeth, Supply, Philip, Svensson, Erik, Tagliani, Elisa, Tahseen, Sabira, Takaki, Akiko, Theron, Grant, Torrea, Gabriela, Van Deun, Armand, van Ingen, Jakko, Van Rie, Annelies, van Soolingen, Dick, Vargas Jr, Roger, Venter, Amour, Veziris, Nicolas, Villellas, Cristina, Viveiros, Miguel, Warren, Robin, Wen, Shu'an, Werngren, Jim, Wilkinson, Robert J., Yang, Caie, Yılmaz, F. Ferda, Zhang, Tingting, Zimenkov, Danila, Ismail, Nazir, Köser, Claudio U., and Schön, Thomas

Abstract

Inappropriately high breakpoints have resulted in systematic false-susceptible AST results to anti-TB drugs. MIC, PK/PD and clinical outcome data should be combined when setting breakpoints to minimise the emergence and spread of antimicrobial resistance.

Published
2022

5. Updating the approaches to define susceptibility and resistance to anti-tuberculosis agents: implications for diagnosis and treatment

Author

Antimycobacterial Susceptibility Testing Group, Georghiou, Sophia B., Rodwell, Timothy C., Korobitsyn, Alexei, Abbadi, Said H., Ajbani, Kanchan, Alffenaar, Jan-Willem, Alland, David, Alvarez, Nataly, Andres, Sönke, Ardizzoni, Elisa, Aubry, Alexandra, Baldan, Rossella, Ballif, Marie, Barilar, Ivan, Böttger, Erik C., Chakravorty, Soumitesh, Claxton, Pauline M., Cirillo, Daniela M., Comas, Iñaki, Coulter, Chris, Denkinger, Claudia M., Derendinger, Brigitta, Desmond, Edward P., Steenwinkel, Jurriaan E. M. de, Dheda, Keertan, Diacon, Andreas H., Dolinger, David L., Dooley, Kelly E., Egger, Matthias, Ehsani, Soudeh, Farhat, Maha R., Fattorini, Lanfranco, Finci, Iris, Fournier Le Ray, Laure, Furió, Victoria, Groenheit, Ramona, Gumbo, Tawanda, Heysell, Scott K., Hillemann, Doris, Hoffmann, Harald, Hsueh, Po-Ren, Hu, Yi, Huang, Hairong, Hussain, Alamdar, Ismail, Farzana, Izumi, Kiyohiko, Jagielski, Tomasz, Johnson, John L., Kambli, Priti, Kaniga, Koné, Karunaratne, G. H. R. Eranga, Sharma, Meenu Kaushal, Keller, Peter M., Kelly, Ellis C., Kholina, Margarita, Kohli, Mikashmi, Kranzer, Katharina, Laurenson, Ian F., Limberis, Jason, Lin, S-Y. Grace, Liu, Yongge, López-Gavín, Alexandre, Lyander, Anna, Machado, Diana, Martínez, Elena, Masood, Faisal, Mitarai, Satoshi, Mvelase, Nomonde R., Niemann, Stefan, Nikolayevskyy, Vladyslav, Maurer, Florian P., Merker, Matthias, Miotto, Paolo, Omar, Shaheed V., Otto-Knapp, Ralf, Palaci, Moisés, Palacios Gutiérrez, Juan José, Peacock, Sharon J., Peloquin, Charles A., Perera, Jennifer, Pierre-Audigier, Catherine, Pholwat, Suporn, Posey, James E., Prammananan, Therdsak, Rigouts, Leen, Robledo, Jaime, Rockwood, Neesha, Rodrigues, Camilla, Salfinger, Max, Schechter, Marcos C., Seifert, Marva, Sengstake, Sarah, Shinnick, Thomas, Shubladze, Natalia, Sintchenko, Vitali, Sirgel, Frederick, Somasundaram, Sulochana, Sterling, Timothy R., Spitaleri, Andrea, Streicher, Elizabeth, Supply, Philip, Svensson, Erik, Tagliani, Elisa, Tahseen, Sabira, Takaki, Akiko, Theron, Grant, Torrea, Gabriela, Van Deun, Armand, van Ingen, Jakko, Van Rie, Annelies, van Soolingen, Dick, Vargas Jr, Roger, Venter, Amour, Veziris, Nicolas, Villellas, Cristina, Viveiros, Miguel, Warren, Robin, Wen, Shu'an, Werngren, Jim, Wilkinson, Robert J., Yang, Caie, Yılmaz, F. Ferda, Zhang, Tingting, Zimenkov, Danila, Ismail, Nazir, Köser, Claudio U., Schön, Thomas, University of Zurich, Antimycobacterial Susceptibility Testing Group, Department of Genetics [Cambridge], University of Cambridge [UK] (CAM), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Médical de l'Institut Pasteur (CMIP), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Institut de médecine et d'épidémiologie appliquée [AP-HP Hôpital Bichat-Claude Bernard] (IMEA), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), As current or former employees or consultants for FIND, the work of R.B. Baldan, I. Comas, C.M. Denkinger, D.L. Dolinger, S.B. Georghiou, C.U. Köser and T.C. Rodwell on the systematic reviews, including this viewpoint, was supported by Unitaid (grant 2019-32-FIND MDR), BMGF (grant OPP1105925), the German Federal Ministry of Education and Research through KfW, the Dutch Ministry of Foreign Affairs, the Australian Department of Foreign Affairs and Trade, and UK aid from the British people. N. Alvarez and J. Robledo are funded by MinCiencias, Colombia (number 221389666216 CT-783-2018). A. Aubry and N. Veziris work at the Centre National de Reference des Mycobactéries, which receives an annual grant from Santé Publique France and have received research grants from Janssen for studies on bedaquiline. P. Claxton and I.F. Laurenson are funded through National Services Scotland. I. Comas was supported by PID2019-104477RB-I00 from the Spanish Science Ministry and by ERC (CoG 101001038). M. Egger is supported by the Swiss National Science Foundation (grant number 320030_153442 and 189498) and the US National Institutes of Health, National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Cancer Institute, the National Institute of Mental Health, the National Institute on Drug Abuse, the National Heart, Lung, and Blood Institute, the National Institute on Alcohol Abuse and Alcoholism, the National Institute of Diabetes and Digestive and Kidney Diseases, the Fogarty International Center, and the National Library of Medicine: Asia-Pacific, U01AI069907, CCASAnet, U01AI069923, Central Africa, U01AI096299, East Africa, U01AI069911, NA-ACCORD, U01AI069918, Southern Africa, U01AI069924, West Africa, U01AI069919. M.R. Farhat is supported by NIH NIAID R01AI155765. S.K. Heysell was funded by NIH NIAID grants R01 AI137080 and U01 AI150508. T. Jagielski was supported by a DAINA grant (number 2017/27/L/NZ6/03279) from the National Science Centre, Poland. J.L. Johnson was supported by contracts NO1-AI95383 and NO1-AI-70022 of the US National Institutes of Health. P.M. Keller was supported by Innosuisse 36198.1 IP-LS. C.U. Köser is a research associate at Wolfson College and visiting scientist at the Department of Genetics, University of Cambridge. The Federal Government of Germany supported C.U. Köser as part of his work for the European Laboratory Initiative, WHO Regional Office for Europe. C.U. Köser was further supported by the Royal Society of Tropical Medicine and Hygiene and the National Institute for Health Research Cambridge Biomedical Research Centre and received an observership by the European Society of Clinical Microbiology and Infectious Diseases to the EUCAST Development Laboratory for Bacteria (Växjö, Sweden), hosted by Gunnar Kahlmeter and Erika Matuschek. D. Machado and M. Viveiros are funded in part by Fundação para a Ciência e a Tecnologia, Portugal (PTDC/BIA-MIC/30692/2017, UID/Multi/04413/2020 and DL57/ CEECIND/0256/2017). S. Niemann is supported by the German Center for Infection Research, Excellenz Cluster Precision Medicine in Chronic Inflammation EXC 2167, Leibniz Science Campus Evolutionary Medicine of the LUNG (EvoLUNG). S.V. Omar has received funding to prepare and provide training for Janssen Pharmaceutica activities. L. Rigouts is supported by the Belgian Directorate General for Development. T.C. Rodwell was additionally funded in part by FIND and NIH NIAD, grants: P30 AI036214 and R21 AI135756. T. Schön is funded by the Swedish Heart and Lung Foundation and the Swedish Research Council. T.R. Sterling has received funding from the US National Institutes of Health and the Centers for Disease Control and Prevention. G. Theron and R. Warren are supported by baseline funding from the South African Medical Research Council. R.J. Wilkinson receives funding from the Wellcome Trust (203135) and from the Francis Crick Institute, which is supported by Cancer Research UK (FC0010218), UKRI (FC0010218) and the Wellcome Trust (FC0010218), Ministerio de Ciencia e Innovación (España), European Research Council, Comas, Iñaki, Comas, Iñaki [0000-0001-5504-9408], Antimycobacterial Susceptibility T, and Wellcome Trust

Subjects
[SDV]Life Sciences [q-bio], Respiratory System, Drug Resistance, Antitubercular Agents, Infektionsmedicin, Medical and Health Sciences, Drug Resistance, Multiple, Bacterial, Tuberculosis, Multidrug-Resistant, 11 Medical and Health Sciences, Human Biology & Physiology, MESH: Microbial Sensitivity Tests, 10179 Institute of Medical Microbiology, Bacterial, Multidrug-Resistant, Infectious Diseases, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Infection, Life Sciences & Biomedicine, Multiple, Model organisms, Pulmonary and Respiratory Medicine, Infectious Medicine, Immunology, Infectious Disease, 610 Medicine & health, Microbial Sensitivity Tests, Vaccine Related, Rare Diseases, Clinical Research, Biodefense, MESH: Drug Resistance, Bacterial, Drug Resistance, Bacterial, Tuberculosis, Humans, Science & Technology, MESH: Humans, Antimycobacterial Susceptibility Testing Group, FOS: Clinical medicine, Prevention, MESH: Drug Resistance, Multiple, Bacterial, Mycobacterium tuberculosis, Eucast, MESH: Antitubercular Agents, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Orphan Drug, Emerging Infectious Diseases, Good Health and Well Being, 2740 Pulmonary and Respiratory Medicine, 570 Life sciences, biology, Human medicine, Antimicrobial Resistance, Model
Abstract

11 páginas, 2 figuras, 1 tabla, Inappropriately high breakpoints have resulted in systematic false-susceptible AST results to anti-TB drugs. MIC, PK/PD and clinical outcome data should be combined when setting breakpoints to minimise the emergence and spread of antimicrobial resistance., I. Comas was supported by PID2019-104477RB-I00 from the Spanish Science Ministry and by ERC (CoG 101001038)

Published
2022

7. Determinants of multidrug-resistant tuberculosis clusters, California, USA, 2004-2007.

Author

Metcalfe, John Z, Metcalfe, John Z, Kim, Elizabeth Y, Lin, S-Y Grace, Cattamanchi, Adithya, Oh, Peter, Flood, Jennifer, Hopewell, Philip C, Kato-Maeda, Midori, Metcalfe, John Z, Metcalfe, John Z, Kim, Elizabeth Y, Lin, S-Y Grace, Cattamanchi, Adithya, Oh, Peter, Flood, Jennifer, Hopewell, Philip C, and Kato-Maeda, Midori

Abstract

Laboratory and epidemiologic evidence suggests that pathogen-specific factors may affect multidrug-resistant (MDR) tuberculosis (TB) transmission and pathogenesis. To identify demographic and clinical characteristics of MDR TB case clustering and to estimate the effect of specific isoniazid resistance-conferring mutations and strain lineage on genotypic clustering, we conducted a population-based cohort study of all MDR TB cases reported in California from January 1, 2004, through December 31, 2007. Of 8,899 incident culture-positive cases for which drug susceptibility information was available, 141 (2%) were MDR. Of 123 (87%) strains with genotype data, 25 (20%) were aggregated in 8 clusters; 113 (92%) of all MDR TB cases and 21 (84%) of clustered MDR TB cases occurred among foreign-born patients. In multivariate analysis, the katG S315T mutation (odds ratio 11.2, 95% confidence interval 2.2-Yen; p = 0.004), but not strain lineage, was independently associated with case clustering.

Published
2010

10. Rapid Drug Susceptibility Testing with a Molecular Beacon Assay Is Associated with Earlier Diagnosis and Treatment of Multidrug-Resistant Tuberculosis in California

Author

Banerjee, Ritu, primary, Allen, Jennifer, additional, Lin, S.-Y. Grace, additional, Westenhouse, Janice, additional, Desmond, Ed, additional, Schecter, Gisela F., additional, Scott, Cheryl, additional, Raftery, Ann, additional, Mase, Sundari, additional, Watt, James P., additional, and Flood, Jennifer, additional

Published
2010
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14. Pyrosequencing for Rapid Detection of Extensively Drug-Resistant Mycobacterium tuberculosisin Clinical Isolates and Clinical Specimens

Author

Lin, S.-Y. Grace, Rodwell, Timothy C., Victor, Thomas C., Rider, Errin C., Pham, Lucy, Catanzaro, Antonino, and Desmond, Edward P.

Abstract

ABSTRACTTreating extensively drug-resistant (XDR) tuberculosis (TB) is a serious challenge. Culture-based drug susceptibility testing (DST) may take 4 weeks or longer from specimen collection to the availability of results. We developed a pyrosequencing (PSQ) assay including eight subassays for the rapid identification of Mycobacterium tuberculosiscomplex (MTBC) and concurrent detection of mutations associated with resistance to drugs defining XDR TB. The entire procedure, from DNA extraction to the availability of results, was accomplished within 6 h. The assay was validated for testing clinical isolates and clinical specimens, which improves the turnaround time for molecular DST and maximizes the benefit of using molecular testing. A total of 130 clinical isolates and 129 clinical specimens were studied. The correlations between the PSQ results and the phenotypic DST results were 94.3% for isoniazid, 98.7% for rifampin, 97.6% for quinolones (ofloxacin, levofloxacin, or moxifloxacin), 99.2% for amikacin, 99.2% for capreomycin, and 96.4% for kanamycin. For testing clinical specimens, the PSQ assay yielded a 98.4% sensitivity for detecting MTBC and a 95.8% sensitivity for generating complete sequencing results from all subassays. The PSQ assay was able to rapidly and accurately detect drug resistance mutations with the sequence information provided, which allows further study of the association of drug resistance or susceptibility with each mutation and the accumulation of such knowledge for future interpretation of results. Thus, reporting of false resistance for mutations known not to confer resistance can be prevented, which is a significant benefit of the assay over existing molecular diagnostic methods endorsed by the World Health Organization.

Published
2014
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15. Lipoprotein Processing Is Essential for Resistance of Mycobacterium tuberculosisto Malachite Green

Author

Banaei, Niaz, Kincaid, Eleanor Z., Lin, S.-Y. Grace, Desmond, Edward, Jacobs, William R., and Ernst, Joel D.

Abstract

ABSTRACTMalachite green, a synthetic antimicrobial dye, has been used for over 50 years in mycobacterial culture medium to inhibit the growth of contaminants. The molecular basis of mycobacterial resistance to malachite green is unknown, although the presence of malachite green-reducing enzymes in the cell envelope has been suggested. The objective of this study was to investigate the role of lipoproteins in resistance of Mycobacterium tuberculosisto malachite green. The replication of an M. tuberculosislipoprotein signal peptidase II (lspA) mutant (ΔlspA::lspAmut) on Middlebrook agar with and without 1 mg/liter malachite green was investigated. The lspAmutant was also compared with wild-type M. tuberculosisin the decolorization rate of malachite green and sensitivity to sodium dodecyl sulfate (SDS) detergent and first-line antituberculosis drugs. The lspAmutant has a 104-fold reduction in CFU-forming efficiency on Middlebrook agar with malachite green. Malachite green is decolorized faster in the presence of the lspAmutant than wild-type bacteria. The lspAmutant is hypersensitive to SDS detergent and shows increased sensitivity to first-line antituberculosis drugs. In summary, lipoprotein processing by LspA is essential for resistance of M. tuberculosisto malachite green. A cell wall permeability defect is likely responsible for the hypersensitivity of lspAmutant to malachite green.

Published
2009
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16. Rapid Detection of Isoniazid and Rifampin Resistance Mutations in Mycobacterium tuberculosisComplex from Cultures or Smear-Positive Sputa by Use of Molecular Beacons

Author

Lin, S.-Y. Grace, Probert, William, Lo, Melanie, and Desmond, Edward

Abstract

ABSTRACTThe slow-growing nature of Mycobacterium tuberculosiscomplex hinders the improvement of turnaround time for phenotypic drug susceptibility testing. We designed a set of molecular beacons for the detection of isoniazid and rifampin resistance mutations in M. tuberculosiscomplex organisms from cultures or from N-acetyl-l-cysteine-NaOH-treated, smear-positive specimens. The performance of the molecular beacons was characterized by studying a total of 196 clinical isolates (127 drug-resistant isolates and 69 drug-susceptible isolates). For detection of isoniazid resistance, the sensitivity and specificity of the assay were 82.7 and 100%, and the positive predictive value (PPV) and negative predictive value (NPV) at a resistance prevalence of 10% were 100 and 98.11%, respectively. For detection of rifampin resistance, the sensitivity and specificity of the assay were 97.5 and 100%, and the PPV and NPV at a resistance prevalence of 2.0% were 100 and 99.95%, respectively.

Published
2004
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