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.

Introduction: Positron emission tomography (PET) using F-18 ßuorodeoxyglucose (FDG) is a promising new imaging modality for bone infections. The method is based on intensive cellular use of glucose during infection. The aim of the current study was to establish the FDG-PET characteristics of normal bone healing and bone infection under standardized conditions. Methods: A modiþed osteomyelitis model of Mader and Fitzgerald was applied in the rabbit (n=12). A metaphyseal defect of the proximal tibia was þlled with bone cement. A predetermined amount (0.1 ml) of Staphylococcus aureus (strain 52/52A/80, 1x10⁵/ml) suspension was injected into the defect. The control animals received an equal saline injection without bacteria. Bone cement was removed from each animal at 2 weeks. During the follow-up, FDG-PET and pQCT were performed at 3 weeks and 6 weeks. Osteomyelitis was conþrmed with bacterial cultures at the time of cement removal and again at sacriþce at 6 weeks. Results: Compared with the contralateral intact tibia, control defects healing without infection showed an increased uptake (p=0.019) at 3 weeks but their FDG-PET tended to normalize within 6 weeks. In the osteomyelitis group, the uptake did not decrease over time and was signiþcantly (p< 0.001) increased both at 3 weeks and at 6 weeks compared with intact bone uptake. The uptake of the infected region was also signiþcantly higher than that of non-infected control defects. Conclusions: Standardized osteomyelitis of the current model was shown to result in an intense continuous FDG-PET activation, which is higher than the transient response of a healing bone defect.