A Randomized Study Evaluating Oral Fusidic Acid (CEM-102) in Combination With Oral Rifampin Compared With Standard-of-Care Antibiotics for Treatment of Prosthetic Joint Infections: A Newly Identified Drug-Drug Interaction.
Journal Article
Background
Fusidic acid (FA) has been used for decades for bone infection, including prosthetic joint infection (PJI), often in combination with rifampin (RIF). An FA/RIF pharmacokinetic interaction has not previously been described.Methods
In a phase 2 open-label randomized study, we evaluated oral FA/RIF vs standard-of-care (SOC) intravenous antibiotics for treatment of hip or knee PJI. Outcome assessment occurred at reimplantation (week 12) for subjects with 2-stage exchange, and after 3 or 6 months of treatment for subjects with hip or knee debride and retain strategies, respectively.Results
Fourteen subjects were randomized 1:1 to FA/RIF or SOC. Pharmacokinetic profiles were obtained for 6 subjects randomized to FA/RIF. FA concentrations were lower than anticipated in all subjects during the first week of therapy, and at weeks 4 and 6, blood levels continued to decline. By week 6, FA exposures were 40%-45% lower than expected.Conclusions
The sponsor elected to terminate this study due to a clearly illustrated drug-drug interaction between FA and RIF, which lowered FA levels to a degree that could influence subject outcomes. Optimization of FA exposure if used in combination with RIF should be a topic of future research.Clinical trials registration
NCT01756924.Full Text
Duke Authors
Cited Authors
- Pushkin, R; Iglesias-Ussel, MD; Keedy, K; MacLauchlin, C; Mould, DR; Berkowitz, R; Kreuzer, S; Darouiche, R; Oldach, D; Fernandes, P
Published Date
- December 2016
Published In
- Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America
Volume / Issue
- 63 / 12
Start / End Page
- 1599 - 1604
PubMed ID
- 27682068
Pubmed Central ID
- 27682068
Electronic International Standard Serial Number (EISSN)
- 1537-6591
International Standard Serial Number (ISSN)
- 1058-4838
Digital Object Identifier (DOI)
- 10.1093/cid/ciw665
Language
- eng