In the field of local application of antimicrobials, a number of novel drugs and/or new drug delivery systems have been developed in recent years. The present study aimed to investigate
hydroxyapatite cement (HAC) as a carrier for
vancomycin in the treatment of chronic
osteomyelitis due to Staphylococcus aureus strains with various mechanisms of resistance. The release of
vancomycin from standard test cylinders was determined in vitro and the efficacy of the delivery system was measured in vivo using a rabbit model of chronic
osteomyelitis. First, powdered HAC was mixed with
vancomycin at 80, 160 and 240 mg/g. After hardening, formed cylinders were eluted in
phosphate buffer and
antibiotic release was measured by
agar diffusion. High levels of release (1512+/-318 to 1937+/-336 microg/ml) were obtained for 12 to 20 days depending on the dosage of
vancomycin. Additionally, bone
infection was induced in the tibia of 30 New Zealand white rabbits by injecting either a methicillin-resistant S. aureus strain (MRSA) or a S. aureus strain with a small colony variant (SCV) phenotype. After 3 weeks (
chronic infection), all animals were treated by
debridement. Moreover, group 1 (challenged with SCVs) and group 2 (challenged with MRSA) were treated by filling the marrow with HAC alone, whereas in groups 3 (SCVs) and 4 (MRSA) the marrow was filled with HAC/
vancomycin (160 mg/g). After 6 weeks all animals were sacrificed. At 3 weeks, pathogens were detected in 24 of 30 animals. All swabs of the control groups, positive for S. aureus on day 21, were also positive on day 42 and S. aureus strains recovered were shown to be clonal to the strains used for induction of
osteomyelitis. By contrast, no growth was found in the treatment group following 7 days of incubation in BHI bouillon. HAC/
vancomycin-treated animals showed no histological evidence of
infection on day 42. In the other groups, different stages of chronic
osteomyelitis were found histologically. No local or systemic side effects due to HAC or
vancomycin were seen. HAC is an effective carrier material for
antibiotic compounds even in refractory
infections due to MRSA or S. aureus SCVs.