Abstract
Introduction: Drug delivery systems (DDSs) using resorbable materials have been developed for local therapy of adult osteomyelitis. An ideal DDS would provide controlled release of antibiotic for an extended period and have an osteoconductive component for spontaneous restoration of bone stock.
Materials and Methods: The developed DDS consisted of three components: poly(DL)-lactide (PDLLA), ciprofloxacin (AB) and bioactive glass (BG) as the osteoconductive component. Based on in vitro studies, the composite provides a long-lasting release (> 3 months) of the ciprofloxacin at therapeutic levels. The localized osteomyelitis model (Stage IIIA) was applied in adult male New Zealand white rabbits (n=30). A cortical bone window was drilled in the proximal tibial metaphysis and filled with bone cement. 0.1 ml of Staphylococcus aureus lxl05 1/ml was injected into the defect. Infection was allowed to develop for two weeks, when the bone cement was surgically removed (debridement) and osteomyelitis was confirmed by positive bacteriology. In treated experimental animals, antibiotic containing composite (AB-PDLLA-BG) was impacted into the infected medullary space. In untreated infection control group, the infected the medullary space was subjected only to surgical debridement. In sham-treated control group, the infected medullary space was filled with a composite without antibiotic (PDLLA-BG). In the negative control group, the injection of bacterial suspension was replaced by saline injection. The treatment response was evaluated by FDG-PET and pQCT at 3 and 6 weeks. Concentration of ciprofloxacin was also measured from bone tissue. The statistical significance of the differences was calculated using paired t-test and one-way ANOVA with Tukey t-test.
Results: Before infection treatment, 96% of the animals had positive bacterial cultures, while none of the negative control group had positive cultures. At sacrifice, all animals in untreated and sham-treated control groups had culture positive infection, while all bone cultures were negative in treated animals. However, three treated animals had culture positive soft-tissue infection. In untreated infection control group, the FDG uptake was increased many-fold compared with the negative control group both at 3 and 6 weeks. The treatment with AB-PDLLA-BG significantly decreased the FDG uptake and the difference was highly significant (p=0.013) compared the untreated animals. Based on pQCT imaging, the cortical defect healing was faster in treated and negative control animals than in untreated and sham-treated groups. In treated animals, the local therapy resulted in high bone concentration of ciprofloxacin.
Conclusions: The current experiment confirmed by collaborative results of both bacteriologic, FDG-PET and pQCT studies that the local infection therapy by the selected antibiotic composite was successful in bone eradication of Staphylococcus aureus pathogen.
The abstracts were prepared by editorial secretary, Mrs K. Papastefanou. Correspondence should be addressed to Professor K.N. Malizos, Department of Orthopaedic Surgery, School of Medicine, University of Thessalia, Larissa, 41222 GREECE
