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.

Published

Journal Article

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. 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. 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. 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. 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

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