Evaluation of biodegradable cefazolin sodium microspheres for the prevention of infection in rabbits with experimental open tibial fractures stabilized with internal fixation

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Abstract
Immediate internal fixation of severe open tibial fractures usually is contraindicated due to the high risk of infection. The objective of this study was to evaluate the efficacy of local antibiotic therapy with biodegradable poly‐(DL‐lactide‐co‐glycolide) cefazolin‐loaded microspheres for the prevention of infection in experimental open fractures stabilized with internal fixation. Rabbits with experimental tibial fractures that were contaminated with Staphylococcus aureus were treated with local application of cefazolin microspheres, an equivalent local dose of free Ancef powder, or systemic Ancef therapy. The bones then were fixed with a four‐hole plate, and the animals were observed for 8 weeks. Clinically, deep infection was present in 86% of control animals that received no antibiotics and in 60% of animals that received a 7 day course of systemic Ancef therapy. In contrast, no infections were noted among any of the surviving rabbits that received local therapy with either cefazolin microspheres or free Ancef powder. Significantly higher levels of serum cefazolin were measured at 1 h for animals treated with free Ancef powder (18.7 ± 6.1 μg/ml) than for those treated with cefazolin microspheres (0.57 ± 0.27 μg/ml). Follow‐up studies are in progress to evaluate further the potential clinical benefits of local antibiotic therapy for the management of contaminated open fractures in humans.