{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T06:07:33Z","timestamp":1774332453721,"version":"3.50.1"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,1,19]],"date-time":"2021-01-19T00:00:00Z","timestamp":1611014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["1R01HD099756-02"],"award-info":[{"award-number":["1R01HD099756-02"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold><jats:italic>Mycobacterium<\/jats:italic><jats:italic>tuberculosis<\/jats:italic> [<jats:italic>Mtb<\/jats:italic>] could be present in different metabolic population in the lung lesions, and nonreplicating persisters [NRP], associated with latent tuberculosis [TB], are the most difficult to kill.<\/jats:p><jats:p><jats:bold>Objective:<\/jats:bold> Test the combination of tedizolid, moxifloxacin, and faropenem for activity against NRP using <jats:italic>Mtb<\/jats:italic> SS18b in the hollow fiber model [HFS-TB].<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Tedizolid and moxifloxacin were tested as, first, two-drug combination against log-phase growth [LPG] and, second, slowly replicating bacilli [SRB] under acidic condition and with faropenem to create a three-drug combination regimen. Finally, standard regimen [isoniazid-rifampin-pyrazinamide] was used as comparator in the HFS-TB experiment with NRP <jats:italic>Mtb<\/jats:italic>. HFS-TB units were sampled for drug-concentration measurement as well as for estimation of bacterial burden using solid agar and mycobacterial growth indicator tube [MGIT] method. Linear regression was used to calculate the kill slopes with each treatment regimen and analysis of variance (ANOVA) to compare the regimen.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Tedizolid at standard dose in combination with high-dose moxifloxacin killed 3.05 log<jats:sub>10<\/jats:sub>\u00a0CFU\/ml LPG <jats:italic>Mtb<\/jats:italic> and 7.37 log<jats:sub>10<\/jats:sub>\u00a0CFU\/ml SRB in the bactericidal and sterilizing activity HFS-TB experiments, respectively. There was no statistical difference between tedizolid-moxifloxacin-faropenem combination and the standard regimen as both killed 7.35 log<jats:sub>10<\/jats:sub>\u00a0CFU\/ml NRP <jats:italic>Mtb<\/jats:italic> in 21\u00a0days. There was no emergence of resistance to any of the drugs studied in the three HFS-TB experiments.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> The experimental regimen of tedizolid, moxifloxacin, and faropenem could effectively kill NRP population of <jats:italic>Mtb<\/jats:italic>, and given the efficacy against different metabolic population of <jats:italic>Mtb<\/jats:italic> could serve as a pan-TB regimen. Clinical studies are warranted to validate the <jats:italic>in vitro<\/jats:italic> findings.<\/jats:p>","DOI":"10.3389\/fphar.2020.616294","type":"journal-article","created":{"date-parts":[[2021,1,19]],"date-time":"2021-01-19T05:05:05Z","timestamp":1611032705000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Tedizolid, Faropenem, and Moxifloxacin Combination With Potential Activity Against Nonreplicating Mycobacterium tuberculosis"],"prefix":"10.3389","volume":"11","author":[{"given":"Shashikant","family":"Srivastava","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kayle N.","family":"Cirrincione","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Devyani","family":"Deshpande","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tawanda","family":"Gumbo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,1,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1038\/nrmicro2236","article-title":"The spectrum of latent tuberculosis: rethinking the biology and intervention strategies","volume":"7","author":"Barry","year":"2009","journal-title":"Nat. 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