{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T23:37:57Z","timestamp":1779233877725,"version":"3.51.4"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1010823","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T00:00:00Z","timestamp":1687910400000}}],"reference-count":88,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2023,6,15]],"date-time":"2023-06-15T00:00:00Z","timestamp":1686787200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["R01AI50684"],"award-info":[{"award-number":["R01AI50684"]}]},{"name":"National Institute of Health","award":["U01HL131072"],"award-info":[{"award-number":["U01HL131072"]}]},{"name":"National Institute of Health","award":["S10OD023524"],"award-info":[{"award-number":["S10OD023524"]}]},{"name":"Wellcome Leap \u0394Tissue Program"},{"DOI":"10.13039\/100000865","name":"Bill & Melinda Gates Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>\n                    Tuberculosis (TB) continues to be one of the deadliest infectious diseases in the world, causing ~1.5 million deaths every year. The World Health Organization initiated an\n                    <jats:italic>End TB Strategy<\/jats:italic>\n                    that aims to reduce TB-related deaths in 2035 by 95%. Recent research goals have focused on discovering more effective and more patient-friendly antibiotic drug regimens to increase patient compliance and decrease emergence of resistant TB. Moxifloxacin is one promising antibiotic that may improve the current standard regimen by shortening treatment time. Clinical trials and\n                    <jats:italic>in vivo<\/jats:italic>\n                    mouse studies suggest that regimens containing moxifloxacin have better bactericidal activity. However, testing every possible combination regimen with moxifloxacin either\n                    <jats:italic>in vivo<\/jats:italic>\n                    or clinically is not feasible due to experimental and clinical limitations. To identify better regimens more systematically, we simulated pharmacokinetics\/pharmacodynamics of various regimens (with and without moxifloxacin) to evaluate efficacies, and then compared our predictions to both clinical trials and nonhuman primate studies performed herein. We used\n                    <jats:italic>GranSim<\/jats:italic>\n                    , our well-established hybrid agent-based model that simulates granuloma formation and antibiotic treatment, for this task. In addition, we established a multiple-objective optimization pipeline using\n                    <jats:italic>GranSim<\/jats:italic>\n                    to discover optimized regimens based on treatment objectives of interest, i.e., minimizing total drug dosage and lowering time needed to sterilize granulomas. Our approach can efficiently test many regimens and successfully identify optimal regimens to inform pre-clinical studies or clinical trials and ultimately accelerate the TB regimen discovery process.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1010823","type":"journal-article","created":{"date-parts":[[2023,6,15]],"date-time":"2023-06-15T14:18:25Z","timestamp":1686838705000},"page":"e1010823","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":20,"title":["Optimizing tuberculosis treatment efficacy: Comparing the standard regimen with Moxifloxacin-containing regimens"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7934-4230","authenticated-orcid":true,"given":"Maral","family":"Budak","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph M.","family":"Cicchese","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pauline","family":"Maiello","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. Jacob","family":"Borish","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander G.","family":"White","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harris B.","family":"Chishti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaime","family":"Tomko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L. 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J.","family":"Linderman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7874-8981","authenticated-orcid":true,"given":"JoAnne L.","family":"Flynn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1053-2591","authenticated-orcid":true,"given":"Denise E.","family":"Kirschner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,6,15]]},"reference":[{"key":"pcbi.1010823.ref001","volume-title":"Global tuberculosis report 2022","author":"World Health Organization","year":"2022"},{"issue":"1","key":"pcbi.1010823.ref002","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1002\/med.21602","article-title":"An overview of new antitubercular drugs, drug candidates, and their targets.","volume":"40","author":"A 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