Bisphosphonate-ciprofloxacin bound to Skelite™ is a prototype for enhancing experimental local antibiotic delivery to injured bone

Abstract

Background: The risk of osteomyelitis after open bone fracture may be reduced by locally applied antibiotics. ENC-41-HP (E41), which comprises ciprofloxacin linked to a 'bone seeking' bisphosphonate, loaded on to carrier Skelite calcium phosphate granules (E41-Skelite™) has favourable in vitro characteristics for application to wounded bone. This study assessed E41-Skelite™ in a rat model of acute tibial osteomyelitis. Methods: Mechanically induced tibial troughs were contaminated with approximately log10 4 colony forming units (c.f.u.) of Staphylococcus aureus (Cowan 1 strain) 'resistant' to E41 (minimum inhibitory concentration 8-16 μg/ml), lavaged and packed with Skelite alone, or with E41-Skelite™ slurry. Animals were killed at 24 h (n = 62), 72 h (n = 46) or 14 days (n = 12), and each tibia was assessed for S. aureus load (c.f.u./g tibia) and histological appearance (14 days only). Results: At 24 and 72 h, the tibias of rats treated with E41-Skelite™ (n = 54) had a significantly lower mean(s.e.m.) load of S. aureus than animals that received Skelite alone (n = 54): log10 3.6(0.2) versus 6.4(0.1) c.f.u./g respectively at 24 h (P < 0.001, Mann-Whitney rank sum test) and log10 4.4(0.2) versus 6.6(0.1) c.f.u./g at 72 h (P < 0.001). At 14 days, E41-Skelite™-treated tibias had fewer bacteria, no signs of osteomyelitis and histological signs of healing. Conclusions: E41-Skelite™, a prototype granulated topical antibiotic delivery system, reduced the development of infection in experimental bone wounds.