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.

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.

Extraarticular abrasive wear in cemented and cementless total knee arthroplasty.

In this study, we examine the contributions of periprosthetic impingement to a seldom recognized source of PE damage resulting in gouging, abrasion, and severe localized damage in cemented and cementless total knee replacement. One hundred sixty two tibial components of 34 different designs in a retrieval collection were examined. The presence and location of abrasive wear to the nonarticulating edges of the insert were measured, with representative specimens examined using SEM. Significant abrasive wear was observed in 35% of the retrievals with cemented femoral components and 25% from noncemented components. Within the group of worn inserts, abrasive scars were seen with a frequency of 75% on the extreme medial edge, 20% on the extreme lateral edge, 26% on the posteromedial edge, and 16% on the posterolateral edge. The role of extraarticular impingement in this damage mode was confirmed by examination of retrieved femoral components with overhanging cement or embedded osteophytes. In the majority of cases, this complication may be avoided by careful removal of excess cement and extracortical osteophytes.