{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T07:57:05Z","timestamp":1774339025170,"version":"3.50.1"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2019,11,12]],"date-time":"2019-11-12T00:00:00Z","timestamp":1573516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Critical Path to TB Regimens"},{"name":"Critical Path Institute","award":["OPP1031105"],"award-info":[{"award-number":["OPP1031105"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Animal models have suggested that the combination of pretomanid with pyrazinamide and moxifloxacin (PaMZ) may shorten TB therapy duration to 3\u20134\u2009months. Here, we tested that in the hollow-fibre system model of TB (HFS-TB).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A series of HFS-TB experiments were performed to compare the kill rates of the PaMZ regimen with the standard three-drug combination therapy. HFS-TB experiments were performed with bacilli in log-phase growth treated for 28\u2009days, intracellular bacilli treated daily for 28\u2009days and semi-dormant Mycobacterium tuberculosis treated with daily therapy for 56\u2009days for sterilizing effect. Next, time-to-extinction equations were employed, followed by morphism transformation and Latin hypercube sampling, to determine the proportion of patients who achieved a time to extinction of 3, 4 or 6\u2009months with each regimen.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Using linear regression, the HFS-TB sterilizing effect rates of the PaMZ regimen versus the standard-therapy regimen during the 56\u2009days were 0.18 (95% credible interval=0.13\u20130.23) versus 0.15 (95% credible interval=0.08\u20130.21) log10\u2009cfu\/mL\/day, compared with 0.16 (95% credible interval=0.13\u20130.18) versus 0.11 (95% credible interval=0.09\u20130.13) log10\u2009cfu\/mL\/day in the Phase II clinical trial, respectively. Using time-to-extinction and Latin hypercube sampling modelling, the expected percentages of patients in which the PaMZ regimen would achieve sterilization were 40.37% (95% credible interval=39.1\u201341.34) and 72.30% (95% credible interval=71.41\u201373.17) at 3 and 4\u2009months duration of therapy, respectively, versus 93.67% (95% credible interval=93.18\u201394.13) at 6\u2009months for standard therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The kill rates of the PaMZ regimen were predicted to be insufficient to achieve cure in less than 6\u2009months in most patients.<\/jats:p><\/jats:sec>","DOI":"10.1093\/jac\/dkz460","type":"journal-article","created":{"date-parts":[[2019,11,7]],"date-time":"2019-11-07T04:27:44Z","timestamp":1573100864000},"page":"392-399","source":"Crossref","is-referenced-by-count":17,"title":["Duration of pretomanid\/moxifloxacin\/pyrazinamide therapy compared with standard therapy based on time-to-extinction mathematics"],"prefix":"10.1093","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8786-8851","authenticated-orcid":false,"given":"Shashikant","family":"Srivastava","sequence":"first","affiliation":[{"name":"Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Devyani","family":"Deshpande","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gesham","family":"Magombedze","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, TX, 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USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Berg","sequence":"additional","affiliation":[{"name":"Critical Path to TB Drug Regimens, Critical Path Institute, Tucson, AZ, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debra","family":"Hanna","sequence":"additional","affiliation":[{"name":"Critical Path to TB Drug Regimens, Critical Path Institute, Tucson, AZ, USA"},{"name":"Bill & Melinda Gates Foundation, Seattle, WA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus","family":"Romero","sequence":"additional","affiliation":[{"name":"Critical Path to TB Drug Regimens, Critical Path Institute, Tucson, AZ, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dave","family":"Hermann","sequence":"additional","affiliation":[{"name":"Bill & Melinda Gates Foundation, Seattle, WA, 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