Tobramycin-impregnated Calcium Sulfate Prevents Infection in Contaminated Wounds

Abstract

Open fractures often are associated with increased rates of infection and nonunion, multiple surgical procedures, and delayed return to preinjury activity. Antimicrobial bone graft substitutes used as an alternative to antibiotic cement beads and/or delayed autologous bone grafting may provide a useful adjunct in patients with open fractures. A stable, unicortical defect was created and contaminated with 30 microL of 5 x 10 colony-forming units/mL of Staphylococcus aureus in the proximal tibial metaphysis of Spanish goats. The negative control group received no treatment, the carrier group received synthetic bone graft alone, the positive control group received tobramycin antibiotic cement, and the treatment group received tobramycin antimicrobial synthetic bone graft (calcium sulfate). After a 3-week evaluation period, intraosseous microbiologic specimens were obtained. The Staphylococcus aureus contaminant was recovered in 11 of 12 animals (mean = 6.9 x 10 colony-forming units/g marrow) in the negative control group and in all animals (mean = 2.2 x 10 colony-forming units/g marrow) in the carrier group. Bacteria were not found in the antibiotic-treated groups. The tobramycin-impregnated calcium sulfate was effective in preventing infection in a contaminated defect. It could be beneficial in reducing the number of surgeries and recovery time because it is bioabsorbable and osteoconductive.

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.…”

“…In the most difficult cases, multiple debridements and prolonged antibiotic therapy are required over several weeks to complete treatment. 4,5 Antibiotic toxicity, side effects, and evolution of bacterial resistance are problems associated with this course of therapy. 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.…”

“…4,5 Antibiotic toxicity, side effects, and evolution of bacterial resistance are problems associated with this course of therapy. 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.…”

“…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.…”

Evaluation of Two Sources of Calcium Sulfate for a Local Drug Delivery System: A Pilot Study

“…CaSO 4 is a biocompatible, biodegradable material with osteoconductive properties that exhibits a bolus, or burst, release followed by an extended drug release from several hours to weeks depending on the formulation [11,23]. CaSO 4 has been used to deliver vancomycin, gentamycin, tobramycin, lincomycin, cefazolin, teicoplanin, and fucidin [4,10,16].…”