{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T03:44:14Z","timestamp":1764906254095,"version":"3.41.2"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T00:00:00Z","timestamp":1736467200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"European Union\u2019s Horizon 2020","award":["823890"],"award-info":[{"award-number":["823890"]}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/04750\/2020","LA\/P\/0064\/2020","2020.09390.BD"],"award-info":[{"award-number":["UIDB\/04750\/2020","LA\/P\/0064\/2020","2020.09390.BD"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004895","name":"FSE","doi-asserted-by":"publisher","award":["CM22\/00246"],"award-info":[{"award-number":["CM22\/00246"]}],"id":[{"id":"10.13039\/501100004895","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Instituto Carlos III"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Higher than standard doses of rifampicin could improve the treatment outcome of drug-susceptible tuberculosis (TB) without compromising the safety of patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We performed a systematic review of prospective clinical studies including adults with pulmonary and extrapulmonary TB receiving rifampicin doses above 10\u2005mg\/kg\/day. We extracted the data on overall adverse events (AE), hepatic AE, sputum culture conversion (SCC) at week 8, recurrence, mortality, and pharmacokinetics. We performed a Bayesian network meta-analysis (NMA) using a random-effects model.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In 19 studies, 2033 out of 3654 participants received rifampicin doses higher than 10\u2005mg\/kg\/day. The NMA showed an increased risk of overall and hepatic AE for the 40\u2005mg\/kg\/day dose (risk ratio [RR] 4.8, 95% credibility interval [CrI]: 1.1, 25, and 15.00; 95% CrI: 1.1, 58.0, respectively), but no other doses, including 50\u2005mg\/kg\/day showed such an increase. Increasing doses improved sputum culture conversion at week 8 (RR 1.3, 95% CrI: 1.1, 1.7 for SCC with 35\u2005mg\/kg\/day).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Optimal doses of rifampicin may be between 25 and 35\u2005mg\/kg\/day, but should be tailored at the individual or, at least, at the population level.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciaf003","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T13:25:32Z","timestamp":1736515532000},"page":"129-142","source":"Crossref","is-referenced-by-count":5,"title":["Safety, Efficacy, and Pharmacokinetics of Daily Optimized Doses of Rifampicin for the Treatment of Tuberculosis: A Systematic Review and Bayesian Network Meta-Analysis"],"prefix":"10.1093","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7238-8337","authenticated-orcid":false,"given":"Juan","family":"Espinosa-Pereiro","sequence":"first","affiliation":[{"name":"International Health Unit Vall d\u2019Hebron-Drassanes, Infectious Diseases Department, Vall d\u2019Hebron University Hospital, Department of Medicine Universitat Aut\u00f3noma de Barcelona, PROSICS Barcelona , Barcelona ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III , Madrid ,","place":["Spain"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6020-8087","authenticated-orcid":false,"given":"Ana","family":"Aguiar","sequence":"additional","affiliation":[{"name":"EPIUnit\u2014Instituto de Sa\u00fade P\u00fablica, Universidade do Porto , Porto ,","place":["Portugal"]},{"name":"Laborat\u00f3rio associado para a Investiga\u00e7\u00e3o Integrativa e Translacional em Sa\u00fade Populacional (ITR) , Porto ,","place":["Portugal"]},{"name":"Sa\u00fade das Popula\u00e7\u00f5es\u2014Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar da Universidade do Porto , Porto ,","place":["Portugal"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8575-325X","authenticated-orcid":false,"given":"Eva","family":"Nara","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biotechnology, Instituto de Investigaciones en Ciencias de la Salud , Asunci\u00f3n ,","place":["Paraguay"]}]},{"given":"Angelica","family":"Medina","sequence":"additional","affiliation":[{"name":"National Program for Tuberculosis, Ministry of Health , Asunci\u00f3n ,","place":["Paraguay"]}]},{"given":"Gladys","family":"Molinas","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Enfermedades Respiratorias y del Ambiente , Asunci\u00f3n ,","place":["Paraguay"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4518-2197","authenticated-orcid":false,"given":"Margarida","family":"Tavares","sequence":"additional","affiliation":[{"name":"EPIUnit\u2014Instituto de Sa\u00fade P\u00fablica, Universidade do Porto , Porto ,","place":["Portugal"]},{"name":"Laborat\u00f3rio associado para a Investiga\u00e7\u00e3o Integrativa e Translacional em Sa\u00fade Populacional (ITR) , Porto ,","place":["Portugal"]},{"name":"Infectious Diseases Department, Centro Hospitalar Universit\u00e3rio de S\u00e3o Jo\u00e3o, Porto , Porto ,","place":["Portugal"]}]},{"given":"Teresa","family":"Tortola","sequence":"additional","affiliation":[{"name":"Microbiology Department, Vall d\u2019Hebron University Hospital, Universitat Aut\u00f2noma de Barcelona , Barcelona ,","place":["Spain"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6028-1460","authenticated-orcid":false,"given":"Samiksha","family":"Ghimire","sequence":"additional","affiliation":[{"name":"Department Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen , Groningen ,","place":["The Netherlands"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6703-0288","authenticated-orcid":false,"given":"Jan-Willem C","family":"Alfenaar","sequence":"additional","affiliation":[{"name":"Department Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen , Groningen ,","place":["The Netherlands"]},{"name":"University of Sydney Institute for Infectious Diseases (Sydney ID), University of Sydney , Sydney, New South Wales ,","place":["Australia"]},{"name":"Faculty of Medicine and Health, The University of Sydney School of Pharmacy, The University of Sydney , Sydney, New South Wales ,","place":["Australia"]},{"name":"Westmead Hospital , Sydney, New South Wales ,","place":["Australia"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3420-0591","authenticated-orcid":false,"given":"Marieke G G","family":"Sturkenboom","sequence":"additional","affiliation":[{"name":"Department Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen , Groningen ,","place":["The Netherlands"]}]},{"given":"Cecile","family":"Magis-Escurra","sequence":"additional","affiliation":[{"name":"Department of Respiratory Diseases-TB expert center Dekkerswald, Radboud University Medical Centre , Nijmegen ,","place":["The Netherlands"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2194-5447","authenticated-orcid":false,"given":"Adri\u00e1n","family":"S\u00e1nchez-Montalva","sequence":"additional","affiliation":[{"name":"International Health Unit Vall d\u2019Hebron-Drassanes, Infectious Diseases Department, Vall d\u2019Hebron University Hospital, Department of Medicine Universitat Aut\u00f3noma de Barcelona, PROSICS Barcelona , Barcelona ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III , Madrid ,","place":["Spain"]},{"name":"Grupo de Estudio de Infecciones por Micobacterias, Sociedad Espa\u00f1ola de Enfermedades Infecciosas y Microbiolog\u00eda Cl\u00ednica (GEIM-SEIMC) , Madrid ,","place":["Spain"]}]},{"given":"Henrique","family":"Barros","sequence":"additional","affiliation":[{"name":"EPIUnit\u2014Instituto de Sa\u00fade P\u00fablica, Universidade do Porto , Porto ,","place":["Portugal"]},{"name":"Laborat\u00f3rio associado para a Investiga\u00e7\u00e3o Integrativa e Translacional em Sa\u00fade Populacional (ITR) , Porto ,","place":["Portugal"]},{"name":"Faculdade de Medicina, Universidade do Porto , Porto ,","place":["Portugal"]}]},{"given":"Raquel","family":"Duarte","sequence":"additional","affiliation":[{"name":"EPIUnit\u2014Instituto de Sa\u00fade P\u00fablica, Universidade do Porto , Porto ,","place":["Portugal"]},{"name":"Laborat\u00f3rio associado para a Investiga\u00e7\u00e3o Integrativa e Translacional em Sa\u00fade Populacional (ITR) , Porto ,","place":["Portugal"]},{"name":"Sa\u00fade das Popula\u00e7\u00f5es\u2014Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar da Universidade do Porto , Porto ,","place":["Portugal"]},{"name":"Instituto de Sa\u00fade P\u00fablica Doutor Ricardo Jorge\u2014INSA , Porto ,","place":["Portugal"]}]}],"member":"286","published-online":{"date-parts":[[2025,1,10]]},"reference":[{"volume-title":"Global tuberculosis report 2023","year":"2023","author":"WHO","key":"2025080104320061000_ciaf003-B1"},{"key":"2025080104320061000_ciaf003-B2","doi-asserted-by":"crossref","first-page":"4331","DOI":"10.1128\/AAC.00912-12","article-title":"Dose-ranging comparison of rifampin and rifapentine in two pathologically distinct murine models of tuberculosis","volume":"56","author":"Rosenthal","year":"2012","journal-title":"Antimicrob 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