The treatment of experimental osteomyelitis by surgical debridement and the implantation of calcium sulfate tobramycin pellets

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.

Preliminary in vitro evaluation of an adjunctive therapy for extremity wound infection reduction: Rapidly resorbing local antibiotic delivery

“…2,5,[7][8][9][13][14][15][16]19 We evaluated the dissolution, elution, and biological activity of fastdegrading drug delivery vehicles made from cellulose binder and calcium sulfate dihydrate and from conventional calcium sulfate alpha-hemihydrate crushed into flakes. While this study used the Yarboro-type crushed conventional cast antibiotic-loaded calcium sulfate pellet as a comparison, the crushing/compressing of commercially available calcium sulfate pellets with tobramycin is not recommended by the manufacturer.…”

“…At 1,4,8,12,24,36,48,72,96,120, and 144 h, pellets were removed, oven dried at 378C for 1 h, and weighed. The pellets were then reimmersed in fresh DI water.…”

“…3) in 20 ml phosphate buffered saline (PBS) in a 378C water bath. At 1,4,8,12,24,36,48,72,96,120,144,168, and 240 h, aliquots were removed and frozen at À408C. At each time point, the pellets were removed and placed in 20 ml fresh PBS.…”

“…5,6 Local delivery systems that place antibiotics directly at the contamination site are favorable alternatives or adjuncts because they minimize systemic toxicity and eliminate concerns about antibiotic penetration. [7][8][9] A local system capable of delivering antibiotics between debridement procedures could help reduce the incidence of infection in musculoskeletal trauma. Use of biodegradable drug delivery systems evades the need for additional surgery required by nonresorbable systems, such as polymethylmethacrylate (PMMA) beads.…”

“…12,13 Calcium sulfate, optimized to resorb at a rate similar to that of new bone formation (several weeks to months) has been combined with antibiotics to eradicate existing bone infections in clinical and experimental situations. 2,5,[7][8][9][13][14][15][16] A calcium sulfate pellet, engineered to dissolve and elute antibiotic over a shorter period of time, may be advantageous for infection prevention.…”