{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T21:28:32Z","timestamp":1784755712906,"version":"3.55.0"},"reference-count":15,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T00:00:00Z","timestamp":1740700800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T00:00:00Z","timestamp":1740700800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-18-CE17-0020"],"award-info":[{"award-number":["ANR-18-CE17-0020"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ann Clin Microbiol Antimicrob"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Objectives<\/jats:title>\n            <jats:p>Rifamycin agents (rifampicin (RIF), rifapentine (RFP), rifabutin (RFB)) are the cornerstone of tuberculosis (TB) therapy. Rifamycins are metabolized into 25-deacetyl-metabolites, which have been described has active and may contribute to <jats:italic>in vivo<\/jats:italic> drug effect. However, little is known about the combined effect of rifamycins and their metabolites across different <jats:italic>Mycobacterium tuberculosis<\/jats:italic> complex (MTBC) lineages.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>This study included 14 MTBC strains representing the main lineages. Minimum inhibitory concentrations (MICs) were determined using microdilution assays for the three rifamycins and their metabolites. A checkerboard assay was used to assess drug interactions, with the fractional inhibitory concentration (FIC) index calculated for synergy or antagonism.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>MICs varied across rifamycins, RIF and its metabolite showed the highest MICs, followed by RFP and RFB and their respective metabolites. FIC indices for rifamycin-metabolite combinations indicated additive effects (FIC between 0.5 and 1.25), with no antagonism observed, even at clinically relevant metabolite-to-parent drug ratios, and without impact of MTBC lineage.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Rifamycin metabolites exhibit additive effects with parent drugs, potentially enhancing bactericidal activity. This highlights that rifamycin susceptibility testing should account for both parent drugs and their metabolites, as these metabolites also exhibit antimicrobial activity. Additionally, these findings support further pharmacokinetic\/pharmacodynamic studies to optimize TB treatment regimens, particularly in relation to metabolite-to-parent drug ratios in patients.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s12941-025-00784-w","type":"journal-article","created":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T18:31:13Z","timestamp":1740767473000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["In vitro activity of rifampicin, rifapentine and rifabutin in combination with their 25-deacetyl-metabolites against various Mycobacterium tuberculosis lineages"],"prefix":"10.1186","volume":"24","author":[{"given":"Charlotte","family":"Genestet","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chlo\u00e9","family":"Bourg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Hodille","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Bahuaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Ader","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvain","family":"Goutelle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oana","family":"Dumitrescu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"On behalf of the Lyon TB study group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,28]]},"reference":[{"key":"784_CR1","unstructured":"WHO G. Global tuberculosis report 2023 [Internet]. 2023 [cited 2024 Oct 21]. Available from: https:\/\/www.who.int\/publications\/i\/item\/9789240083851"},{"key":"784_CR2","doi-asserted-by":"publisher","first-page":"1455","DOI":"10.1002\/cpt.2261","volume":"110","author":"CA Peloquin","year":"2021","unstructured":"Peloquin CA, Davies GR. The treatment of tuberculosis. Clin Pharmacol Ther. 2021;110:1455\u201366.","journal-title":"Clin Pharmacol Ther"},{"key":"784_CR3","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1093\/cid\/ciab097","volume":"73","author":"MA Kendall","year":"2021","unstructured":"Kendall MA, Lalloo U, Fletcher CV, Wu X, Podany AT, Cardoso SW, et al. Safety and Pharmacokinetics of double-dose Lopinavir\/Ritonavir\u2009+\u2009Rifampin Versus Lopinavir\/Ritonavir\u2009+\u2009Daily Rifabutin for Treatment of Human Immunodeficiency Virus-Tuberculosis Coinfection. Clin Infect Dis off Publ Infect Dis Soc Am. 2021;73:706\u201315.","journal-title":"Clin Infect Dis off Publ Infect Dis Soc Am"},{"key":"784_CR4","doi-asserted-by":"publisher","first-page":"eaai7786","DOI":"10.1126\/scitranslmed.aai7786","volume":"10","author":"D Rifat","year":"2018","unstructured":"Rifat D, Prideaux B, Savic RM, Urbanowski ME, Parsons TL, Luna B, et al. Pharmacokinetics of rifapentine and rifampin in a rabbit model of tuberculosis and correlation with clinical trial data. Sci Transl Med. 2018;10:eaai7786.","journal-title":"Sci Transl Med"},{"key":"784_CR5","doi-asserted-by":"publisher","first-page":"1705","DOI":"10.1056\/NEJMoa2033400","volume":"384","author":"SE Dorman","year":"2021","unstructured":"Dorman SE, Nahid P, Kurbatova EV, Phillips PPJ, Bryant K, Dooley KE, et al. Four-Month Rifapentine regimens with or without Moxifloxacin for Tuberculosis. 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Antibiotics. 2022;11:1785.","journal-title":"Antibiotics"},{"key":"784_CR13","doi-asserted-by":"publisher","first-page":"3132","DOI":"10.1111\/bcp.15298","volume":"88","author":"MR Muda","year":"2022","unstructured":"Muda MR, Harun SN, Syed Sulaiman SA, Sheikh Ghadzi SM. Population pharmacokinetics analyses of rifampicin in adult and children populations: a systematic review. Br J Clin Pharmacol. 2022;88:3132\u201352.","journal-title":"Br J Clin Pharmacol"},{"key":"784_CR14","doi-asserted-by":"publisher","first-page":"2200239","DOI":"10.1183\/13993003.00239-2022","volume":"60","author":"Consortium TCr","year":"2022","unstructured":"Consortium TCr. Epidemiological cut-off values for a 96-well broth microdilution plate for high-throughput research antibiotic susceptibility testing of M. Tuberculosis. Eur Respir J. 2022;60:2200239.","journal-title":"Eur Respir J"},{"key":"784_CR15","doi-asserted-by":"publisher","unstructured":"Stanley S, Liu Q, Fortune SM. Mycobacterium tuberculosis functional genetic diversity, altered drug sensitivity, and precision medicine. Front Cell Infect Microbiol [Internet]. 2022 [cited 2024 Dec 27];12. 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