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Fusidic acid rifampin interaction may cause treatment failure in prosthetic joint infections
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A newly identified drug–drug interaction between fusidic acid and oral rifampin lowered fusidic acid to levels that could result in treatment failure among patients with prosthetic joint infections, according to data from a phase 2 study.
The interaction prompted the study sponsor to terminate the trial before completion.
“The combination of fusidic acid and rifampin to treat prosthetic joint infections has demonstrated efficacy and safety at doses similar to those used in this study,” Richard Pushkin, MD, of Cempra Inc., and colleagues wrote. “To date, however, there have been no pharmacokinetic reports of fusidic acid and rifampin given in combination, either from a healthy volunteer drug–drug interaction study or from patients receiving combination therapy.”
Researchers conducted an open-label, randomized study to evaluate fusidic acid and rifampin vs. standard of care antibiotics in patients with hip or knee prosthetic joint infections or spacer infections. Researchers randomly assigned patients to fusidic acid and rifampin (n = 7) or standard of care antibiotics (n = 7). Then they performed pharmacokinetic blood sampling among six participants assigned to fusidic acid and rifampin therapy. Outcome assessment was scheduled for re-implantation (week 12) in patients with a 2-stage surgical exchange, after 3 months in patients with hip debridement and retention strategies and after 6 months in patients with knee debridement and retention strategies.
During the first week of treatment, fusidic acid levels were lower than expected in all patients, Pushkin and colleagues reported. Blood levels continued to decline, with exposures 40% to 45% lower than anticipated at week 6. The reduction in fusidic acid exposure creates an opportunity for rifampin-resistant infection to emerge, Pushkin and colleagues wrote, which could cause treatment failure.
“To summarize, the sponsor elected to terminate this study due to a clearly illustrated drug–drug interaction between fusidic acid and rifampin, which lowered fusidic acid levels to a degree that could influence subject outcomes,” the researchers wrote. “The combination of fusidic acid and rifampin has been used for the treatment of prosthetic joint infection in many parts of the world for decades; however, based on these pharmacokinetic data, optimization of fusidic acid exposure if used in combination with rifampin should be a topic of future research.” – by Andy Polhamus
Disclosure: Pushkin reports he is an employee of Cempra Inc., who funded the study. Please see the full study for a complete list of all other researchers’ relevant financial disclosures.
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