{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T09:07:32Z","timestamp":1788858452818,"version":"build-2803163510"},"reference-count":18,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":7,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Infectious Diseases Research Fund\u2014St Vincent\u2019s Hospital Melbourne"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Fusidic acid with rifampicin is used for the treatment of severe staphylococcal infection, particularly prosthetic joint infections. Previous studies using twice daily fusidic acid showed rifampicin increases fusidic acid clearance, potentially causing sub-therapeutic concentrations. It is uncertain whether this occurs with three-times daily dosing. This study sought to re-evaluate this potential drug\u2013drug interaction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this prospective, open-label drug\u2013drug interaction population pharmacokinetic (PK) study, participants were randomized to receive fusidic acid or rifampicin for 24\u2005hours, followed by combination therapy for the duration of treatment. Drug concentration assays used liquid-chromatography mass spectroscopy on dried blood spots. Population PK models were built for fusidic acid, rifampicin and 25-desacetyl rifampicin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Ten participants were recruited. Inter-individual variability for both absorption (98.1%) and clearance (77.8%) were high for fusidic acid. A population pharmacokinetic model for fusidic acid revealed that early autoinhibition dominated over later rifampicin-mediated induction, resulting in a net decrease in fusidic acid clearance. The mean fusidic acid area under the curve during each dosing interval (AUC\u03c4) at steady state was 1.76-fold [0.049, 34.918] higher relative to Day 1, despite high uncertainty.<\/jats:p>\n                    <jats:p>Large inter-individual (110%) variability in absorption was observed for rifampicin. There was no apparent effect on rifampicin metabolism by fusidic acid co-administration, however, fusidic acid decreased clearance of 25-desacetyl rifampicin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In patients treated with fusidic acid three times daily in combination with rifampicin, autoinhibition potentially counteracted rifampicin induction such that fusidic acid concentrations were not reduced. Rifampicin clearance was not affected by fusidic acid, but 25-desacetyl rifampicin clearance was decreased. There was large inter-individual variability in the observed concentrations and final parameter estimates.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkag293","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T11:19:48Z","timestamp":1786965588000},"source":"Crossref","is-referenced-by-count":0,"title":["A prospective pharmacokinetic interaction study between rifampicin and fusidic acid for the treatment of staphylococcal infections"],"prefix":"10.1093","volume":"81","author":[{"given":"Callum","family":"Maggs","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, St Vincent\u2019s Hospital Melbourne , Fitzroy, Melbourne, Vic ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4334-5351","authenticated-orcid":false,"given":"Laurens","family":"Manning","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Fiona Stanley Hospital , Murdoch, WA ,","place":["Australia"]},{"name":"Medical School, University of Western Australia , Perth ,","place":["Australia"]},{"name":"Wesfarmers Centre for Vaccines and Infectious Diseases, The Kids Research Institute , Nedlands, WA 6009 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Okhee","family":"Yoo","sequence":"additional","affiliation":[{"name":"Wesfarmers Centre for Vaccines and Infectious Diseases, The Kids Research Institute , Nedlands, WA 6009 ,","place":["Australia"]},{"name":"Department of Pharmacy, School of Health and Clinical Sciences, University of Western Australia , Perth, WA 6009 ,","place":["Australia"]},{"name":"Institute for Paediatric Perioperative Excellence, The University of Western Australia , Perth, WA 6009 ,","place":["Australia"]},{"name":"Centre for Optimisation of Medicines, School of Health and Clinical Sciences, University of Western Australia , Perth, WA 6009 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,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7578-882X","authenticated-orcid":false,"given":"Craig","family":"Aboltins","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, St Vincent\u2019s Hospital Melbourne , Fitzroy, Melbourne, Vic ,","place":["Australia"]},{"name":"Department of Medicine, University of Melbourne , Melbourne, Vic ,","place":["Australia"]},{"name":"Department of Infectious Diseases, Northern Health , 185 Cooper St, Epping, Melbourne, Victoria 3076 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"2026090804133556100_dkag293-B1","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1093\/jac\/33.5.959","article-title":"Microbiological tests to predict treatment outcome in experimental device-related infections due to Staphylococcus 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