METHODS: Tobramycin (30 mg/mL) was incorporated into CPB by dipping method and the efficacy of TOB-loaded CPB was studied in a rabbit osteomyelitis model. For juxtaposition, CPB with and without TOB were prepared. Twenty-five New Zealand white rabbits were grouped (n = 5) as sham (group 1), TOB-loaded CPB without S. aureus (group 2), S. aureus only (group 3), S. aureus + CPB (group 4), and S. aureus + TOB-loaded CPB (group 5). Groups infected with S. aureus followed by CPB implantation were immediately subjected to surgery at the mid-shaft of the tibia. After 28 days post-surgery, all rabbits were euthanized and the presence or absence of chronic osteomyelitis and the extent of architectural destruction of the bone were assessed by radiology, bacteriology and histological studies.
RESULTS: Tobramycin-loaded CPB group potentially inhibited the growth of S. aureus causing 3.2 to 3.4 log10 reductions in CFU/g of bone tissue compared to the controls. Untreated groups infected with S. aureus showed signs of chronic osteomyelitis with abundant bacterial growth and alterations in bone architecture. The sham group and TOB-loaded CPB group showed no evidence of bacterial growth.
CONCLUSIONS: TOB-incorporated into CPB for local bone administration was proven to be more successful in increasing the efficacy of TOB in this rabbit osteomyelitis model and hence could represent a good alternative to other formulations used in the treatment of osteomyelitis.
Method: A total of 24 elastomeric devices were prepared, and six elastomeric devices containing 6mg/mL of ceftaroline (three in each type of diluents) were stored at one of the following conditions: 4°C for 6 days, 25°C for 24hours, 30°C for 24hours or 35°C for 24hours. An aliquot was withdrawn before storage and at different time points. Chemical stability was measured using a stability indicating high-performance liquid chromatography, and physical stability was assessed as change in pH, colour and particle content.
Results: Ceftaroline, when admixed with both diluents, was stable for 144, 24 and 12hours at 4°C, 25°C and 30°C, respectively. At 35°C, ceftaroline admixed with normal saline (NS) and glucose 5% was stable for 12hours and for 6hours, respectively. No evidence of particle formation, colour change or pH change was observed throughout the study period.
Conclusions: Our findings support 12 or 24hours continuous elastomeric infusion of ceftaroline-NS admixture, and bulk preparation of elastomeric pumps containing ceftaroline solution in advance. This would facilitate early hospital discharge of patients eligible for the elastomeric-based home therapy and avoid the need for patient's caregivers travelling to the hospital on a daily basis.