{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T19:30:42Z","timestamp":1782156642554,"version":"3.54.5"},"reference-count":50,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2017,2,23]],"date-time":"2017-02-23T00:00:00Z","timestamp":1487808000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,3,1]],"date-time":"2017-03-01T00:00:00Z","timestamp":1488326400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"B. Frank and Kathleen Polk Assistant Professorship in Epidemiology at Johns Hopkins Bloomberg School of Public Health"},{"name":"USAID\/International Union Against Tuberculosis and Lung Disease","award":["GHN-A-OO-08-00004-00"],"award-info":[{"award-number":["GHN-A-OO-08-00004-00"]}]},{"name":"Johns Hopkins University Medical Scientist Training Program","award":["NIH T32 GM007309"],"award-info":[{"award-number":["NIH T32 GM007309"]}]},{"DOI":"10.13039\/100006063","name":"Paul and Daisy Soros Fellowships for New Americans","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100006063","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1084276"],"award-info":[{"award-number":["OPP1084276"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"crossref","award":["Work Order 10"],"award-info":[{"award-number":["Work Order 10"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000265","name":"RCUK | Medical Research Council","doi-asserted-by":"publisher","award":["J005088\/1"],"award-info":[{"award-number":["J005088\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Several infectious diseases of global importance\u2014e.g., HIV infection and tuberculosis (TB)\u2014require prolonged treatment with combination antimicrobial regimens typically involving high-potency core agents coupled with additional companion drugs that protect against the\n            <jats:italic>de novo<\/jats:italic>\n            emergence of mutations conferring resistance to the core agents. Often, the most effective (or least toxic) companion agents are reused in sequential (first-line, second-line, etc.) regimens. We used a multistrain model of\n            <jats:named-content content-type=\"genus-species\">Mycobacterium tuberculosis<\/jats:named-content>\n            transmission in Southeast Asia to investigate how this practice might facilitate the emergence of extensive drug resistance, i.e., resistance to multiple core agents. We calibrated this model to regional TB and drug resistance data using an approximate Bayesian computational approach. We report the proportion of data-consistent simulations in which the prevalence of pre-extensively drug-resistant (pre-XDR) TB\u2014defined as resistance to both first-line and second-line core agents (rifampin and fluoroquinolones)\u2014exceeds predefined acceptability thresholds (1 to 2 cases per 100,000 population by 2035). The use of pyrazinamide (the most effective companion agent) in both first-line and second-line regimens increased the proportion of simulations in which the prevalence exceeded the pre-XDR acceptability threshold by 7-fold compared to a scenario in which patients with pyrazinamide-resistant TB received an alternative drug. Model parameters related to the emergence and transmission of pyrazinamide-resistant TB and resistance amplification were among those that were the most strongly correlated with the projected pre-XDR prevalence, indicating that pyrazinamide resistance acquired during first-line treatment subsequently promotes amplification to pre-XDR TB under pyrazinamide-containing second-line treatment. These findings suggest that the appropriate use of companion drugs may be critical to preventing the emergence of strains resistant to multiple core agents.\n          <\/jats:p>","DOI":"10.1128\/aac.00498-16","type":"journal-article","created":{"date-parts":[[2016,12,13]],"date-time":"2016-12-13T02:30:41Z","timestamp":1481596241000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":21,"title":["A Multistrain Mathematical Model To Investigate the Role of Pyrazinamide in the Emergence of Extensively Drug-Resistant Tuberculosis"],"prefix":"10.1128","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2874-471X","authenticated-orcid":false,"given":"Mariam O.","family":"Fofana","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sourya","family":"Shrestha","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwenan M.","family":"Knight","sequence":"additional","affiliation":[{"name":"TB Modelling Group, TB Centre, Centre for the Mathematical Modelling of Infectious Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ted","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Epidemiology of Microbial Diseases, School of Public Health, Yale University, New Haven, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard G.","family":"White","sequence":"additional","affiliation":[{"name":"TB Modelling Group, TB Centre, Centre for the Mathematical Modelling of Infectious Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Cobelens","sequence":"additional","affiliation":[{"name":"Amsterdam Institute for Global Health and Development, Academic Medical Center, Amsterdam, Netherlands"},{"name":"KNCV Tuberculosis Foundation, The Hague, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Dowdy","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA"},{"name":"Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","volume-title":"Antimicrobial resistance: global report on surveillance 2014","author":"World Health Organization","year":"2014","unstructured":"World Health Organization. 2014. 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