{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T20:09:50Z","timestamp":1792613390847,"version":"4.5.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100018693","name":"Horizon Europe Framework Programme","doi-asserted-by":"crossref","award":["HORIZON-MSCA-2021-PF-GF, number 101063247"],"award-info":[{"award-number":["HORIZON-MSCA-2021-PF-GF, number 101063247"]}],"id":[{"id":"10.13039\/100018693","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100018693","name":"Horizon Europe Framework Programme","doi-asserted-by":"crossref","award":["HORIZON-MSCA-2021-PF-GF, number 101063247"],"award-info":[{"award-number":["HORIZON-MSCA-2021-PF-GF, number 101063247"]}],"id":[{"id":"10.13039\/100018693","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Antibiotic-resistant mycobacterial infections are a major threat to health care. Telacebec is a novel, first-in-class agent targeting mycobacterial cellular energy production in a range of pathogenic mycobacteria, including Mycobacterium tuberculosis, M. leprae, and M. ulcerans.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To explore telacebec\u2019s early bactericidal activity, tolerability, safety, and pharmacokinetics in patients with pulmonary tuberculosis and to summarize its current state of development for other diseases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We randomly assigned 64 patients with smear-positive, drug-sensitive tuberculosis to daily telacebec 100, 200, or 300 mg, or standard four-drug treatment as control, for 14 days.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Sputum collected overnight was cultured in liquid and on solid media to determine the change of viable mycobacteria over time. Safety and tolerability were assessed daily. A full pharmacokinetic profile was obtained on Day 14. We found a dose-dependent reduction of the sputum mycobacterial load with a mean\u2009\u00b1\u2009SD daily change for telacebec 300 mg and control, respectively, of 0.097\u2009\u00b1\u20090.050 and 0.200\u2009\u00b1\u20090.073 log colony-forming units, and 3.738\u2009\u00b1\u20092.747 and 6.853\u2009\u00b1\u20091.194 hours to culture positivity over the first 14 days of treatment. Pharmacokinetics were dose proportional. Telacebec was well tolerated and safe, with low adverse event rates across all doses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results confirm telacebec\u2019s clinical activity against M. tuberculosis. Longer trials, in combination with other agents, are required to validate these results and to investigate telacebec\u2019s full potential. These results encourage the exploration of telacebec for more effective, shorter treatment regimens for leprosy and Buruli ulcer. A clinical trial for Buruli ulcer is under way.<\/jats:p>\n                    <jats:p>Clinical trial registered with URL (NCT 03563599).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202408-1632oc","type":"journal-article","created":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T11:06:42Z","timestamp":1742555202000},"page":"1504-1512","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":20,"title":["Telacebec, a Potent Agent in the Fight against Tuberculosis: Findings from a Randomized, Phase 2 Clinical Trial and Beyond"],"prefix":"10.1093","volume":"211","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0966-3233","authenticated-orcid":false,"given":"Saskia","family":"Janssen","sequence":"first","affiliation":[{"name":"TASK, Cape Town, South Africa"},{"name":"Microbiology Department, Radboud University Medical Center, Nijmegen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caryn","family":"Upton","sequence":"additional","affiliation":[{"name":"TASK, Cape Town, South Africa"},{"name":"Microbiology Department, Radboud University Medical Center, Nijmegen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronique R.","family":"de Jager","sequence":"additional","affiliation":[{"name":"TASK, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christo","family":"van Niekerk","sequence":"additional","affiliation":[{"name":"Qurient Co. 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