No abstract

Calcium sulfate was used as a biodegradable delivery system for the administration of antibiotics in musculoskeletal infection. New Zealand white rabbits were infected with Staplylococcus aureus, debrided, and randomized to one of four treatment groups: calcium sulfate pellets with 10% tobramycin sulfate, placebo calcium sulfate pellets and IM tobramycin, placebo calcium sulfate pellets, or debridement. Serum and wound exudate tobramycin concentrations and serum calcium levels were measured. Radiographs, cultures, and histology were analyzed for efficacy and treatment. Rabbits treated with 10% tobramycin sulfate pellets showed a significantly higher eradication of infection (11/13) than rabbits treated with debridement only (5/12), placebo pellets and IM tobramycin (5/14). or placebo pellets (3/13). In the group receiving 10% tobramycin sulfate pellets, serum tobramycin concentrations peaked 3 h post-operatively at 5.87 microg/ml and were non-detectable after day 1. In the group receiving placebo pellets and IM tobramycin, serum concentrations peaked at 7.82 microg/ml 1 h post-operatively, fell to 6.12 microg/ml on day 2, and averaged 4.18 microg/ ml for the remainder of the treatment period. The wound exudate tobramycin concentrations in the animals treated with tobramycin sulfate pellets peaked at 11.9 mg/ml on day 1 and dropped to 2.5 microg/ml on day 7. There was no significant difference in the serum calcium levels in any of the treatment groups. Calcium sulfate containing tobramycin sulfate has potential utility as a biodegradable local antibiotic delivery system in the treatment of musculoskeletal infections.

No abstract

We demonstrate that coating calcium sulfate with deacetylated chitosan enhances the elution profile of daptomycin by prolonging the period during which high concentrations of antibiotic are released. Coatings reduced initial bolus release of daptomycin by a factor of 10 to approximately 1000 μg/ml, and levels remained above 100 μg/ml for up to 10 days. Chitosan-coated and uncoated calcium sulfate implants with and without 15% daptomycin were evaluated in an experimental model of staphylococcal osteomyelitis through bacteriology scores, radiology, histopathology, and Gram staining. Significant reduction in bacteriology scores was observed for implants containing daptomycin and coated with chitosan compared with all the other groups. We confirm that the use of chitosan-coated calcium sulfate beads for local antibiotic delivery can be correlated with an improved therapeutic outcome following surgical debridement in the treatment of chronic osteomyelitis.

The elution of antibiotics from hand mixed antibiotic-laden polymethylmethacrylate (PMMA) must be increased to achieve clinical performance equivalent to commercially manufactured antibiotic beads (not available in the USA) in the management of musculoskeletal infections. Adding fillers such as glycine and dextran to polymethylmethacrylate increases the elution of antibiotics from antibiotic-laden PMMA. We propose xylitol, a naturally occurring sweetener with direct antibiofilm properties, as a filler material. To compare the efficacy of xylitol and glycine as fillers on the elution of antibiotics from PMMA, elution studies were performed on mixtures of Palacos polymethylmethacrylate and daptomycin (1 gm) with xylitol or glycine as the filler (28 g). Xylitol and glycine enhanced the daptomycin activity eluted from the polymethylmethacrylate. Xylitol was more effective than glycine, having a greater increase in daptomycin release at all data points; on day one xylitol increased the elution of daptomycin 2.67 times whereas glycine increased it 1.78 times also on day one. The eluant concentration of daptomycin remained higher longer for xylitol; 3.90 microg/mL for xylitol versus 2.25 microg/mL for glycine on day 9. Xylitol is inexpensive and readily available. It can be hand mixed with PMMA, and is more effective than glycine as a filler to enhance daptomycin release. Considering possible antibiofilm activity, xylitol may be a more advantageous choice.