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Clin Infect Dis. 2016 Dec 15;63(12):1599-1604. Epub 2016 Sep 28.

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.

Author information

1
Cempra Inc.
2
University of North Carolina, Chapel Hill.
3
Projections Research Inc, Phoenixville, Pennsylvania.
4
Phoenix Clinical Research, Tamarac, Florida.
5
Memorial Bone and Joint Clinic and University of Texas Health Science Center at Houston.
6
Departments of Medicine, Surgery, and Physical Medicine and Rehabilitation, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas.

Abstract

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.

KEYWORDS:

arthroplasty; fusidic acid; prosthetic joint infection; rifampin

PMID:
27682068
DOI:
10.1093/cid/ciw665
[Indexed for MEDLINE]

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