{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T11:35:40Z","timestamp":1778412940072,"version":"3.51.4"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T00:00:00Z","timestamp":1722988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009139","name":"German Center for Infection Research","doi-asserted-by":"publisher","award":["TTU 02.710"],"award-info":[{"award-number":["TTU 02.710"]}],"id":[{"id":"10.13039\/100009139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009139","name":"German Center for Infection Research","doi-asserted-by":"publisher","award":["02.814"],"award-info":[{"award-number":["02.814"]}],"id":[{"id":"10.13039\/100009139","id-type":"DOI","asserted-by":"publisher"}]},{"name":"PanACEA 2"},{"name":"German Ministry for Education and Research"},{"name":"Swiss State Secretariat for Education, Research, and Innovation"},{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>New and shorter regimens against multi-drug resistant tuberculosis (TB) remain urgently needed. To inform treatment duration in clinical trials, this study aimed to identify human pharmacokinetic equivalent doses, antimycobacterial and sterilizing activity of a novel regimen, containing bedaquiline, delamanid, moxifloxacin and sutezolid (BDMU), in the standard mouse model (BALB\/c) of Mycobacterium tuberculosis (Mtb) infection.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Treatment of mice with B25D0.6M200U200, B25D0.6M200, B25D0.6M200(U2003) or H10R10Z150E100 (isoniazid, rifampicin, pyrazinamide, ethambutol, HRZE), started 3 weeks after Mtb infection. Bactericidal activity was assessed after 1, 2, 3 and 4 months of treatment and relapse rates were assessed 3 months after completing treatment durations of 2, 3 and 4 months.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>B25D0.6M200U200 generated human equivalent exposures in uninfected BALB\/c mice. After 1 month of treatment, a higher bactericidal activity was observed for the B25D0.6M200U200 and the B25D0.6M200 regimen compared to the standard H10R10Z150E100 regimen. Furthermore, 3 months of therapy with both BDM-based regimens resulted in negative lung cultures, whereas all H10R10Z150E100 treated mice were still culture positive. After 3 months of therapy 7% and 13% of mice relapsed receiving B25D0.6M200U200 and B25D0.6M200, respectively, compared to 40% for H10R10Z150E100 treatment showing an increased sterilizing activity of both BDM-based regimens.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>BDM-based regimens, with and without sutezolid, have a higher efficacy than the HRZE regimen in the BALB\/c model of TB, with some improvement by adding sutezolid. By translating these results to TB patients, this novel BDMU regimen should be able to reduce treatment duration by 25% compared to HRZE therapy.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkae266","type":"journal-article","created":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T23:55:15Z","timestamp":1723074915000},"page":"2607-2610","source":"Crossref","is-referenced-by-count":3,"title":["Investigating the treatment shortening potential of a combination of bedaquiline, delamanid and moxifloxacin with and without sutezolid, in a murine tuberculosis model with confirmed drug exposures"],"prefix":"10.1093","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7883-4433","authenticated-orcid":false,"given":"Kerstin","family":"Walter","sequence":"first","affiliation":[{"name":"Division of Infection Immunology, Research Center Borstel, Leibniz Lung Center , Borstel ,","place":["Germany"]},{"name":"German Center for Infection Research, Partner Site Hamburg-L\u00fcbeck-Borstel-Riems , Borstel ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lindsey H M","family":"te Brake","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Radboud Institute of Health Sciences, Radboud University Medical Center , Nijmegen ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann-Kathrin","family":"Lemm","sequence":"additional","affiliation":[{"name":"Division of Infection Immunology, Research Center Borstel, Leibniz Lung Center , Borstel ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Hoelscher","sequence":"additional","affiliation":[{"name":"Institute of Infectious Diseases and Tropical Medicine, University Hospital, LMU Munich , Munich ,","place":["Germany"]},{"name":"German Center for Infection Research, Partner Site Munich , Munich ,","place":["Germany"]},{"name":"Fraunhofer Institute 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,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9252-7106","authenticated-orcid":false,"given":"Norbert","family":"Heinrich","sequence":"additional","affiliation":[{"name":"Institute of Infectious Diseases and Tropical Medicine, University Hospital, LMU Munich , Munich ,","place":["Germany"]},{"name":"German Center for Infection Research, Partner Site Munich , Munich ,","place":["Germany"]},{"name":"Fraunhofer Institute ITMP, Immunology, Infection and Pandemic Research , Munich ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,8,7]]},"reference":[{"key":"2024093023514049600_dkae266-B1","article-title":"Global tuberculosis report 2022","author":"WHO"},{"key":"2024093023514049600_dkae266-B2","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1016\/S2468-2667(16)30035-4","article-title":"Emergence of drug resistance in patients 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