Title |
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
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Published in |
Clinical Infectious Diseases, September 2016
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DOI | 10.1093/cid/ciw665 |
Pubmed ID | |
Authors |
Richard Pushkin, Maria D. Iglesias-Ussel, Kara Keedy, Chris MacLauchlin, Diane R. Mould, Richard Berkowitz, Stephan Kreuzer, Rabih Darouiche, David Oldach, Prabha Fernandes |
Abstract |
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 versus standard of care (SOC) IV antibiotics for treatment of hip or knee PJI. Outcome assessment occurred at re-implantation (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 six 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 DDI 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 1 | 50% |
Unknown | 1 | 50% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Practitioners (doctors, other healthcare professionals) | 2 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 56 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 8 | 14% |
Researcher | 7 | 13% |
Other | 6 | 11% |
Student > Master | 5 | 9% |
Student > Bachelor | 4 | 7% |
Other | 12 | 21% |
Unknown | 14 | 25% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 20 | 36% |
Nursing and Health Professions | 5 | 9% |
Agricultural and Biological Sciences | 3 | 5% |
Chemistry | 3 | 5% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 4% |
Other | 6 | 11% |
Unknown | 17 | 30% |