title: In vitro release of vancomycin and tobramycin from impregnated human and bovine bone grafts.
abstract: In order to combine the effects of bone repair and eradication of infection, with both Gram-positive and Gram-negative pathogens, the behaviour of a compound of bone graft and antibiotics was investigated. Samples of human and bovine bone, cancellous and cortical, were processed and incubated with vancomycin and tobramycin, respectively. The compound was placed in 5% human albumin and the surrounding liquid was exchanged completely every 24 h. Concentrations of antibiotics in the fluid were measured over < or = 28 days using high pressure liquid chromatography and a bioassay. All tested combinations eluted mainly in the initial phase with a logarithmic decrease over the testing period. The concentration of antibiotics in the albumin was well above the MIC for common pathogens throughout the investigation in all tested specimens. The highest initial concentrations were measured in the compound of bovine bone together with vancomycin (24395.8 +/- 1138.9 mg/L), decreasing to 9.02 +/- 1.3 mg/L after 11 exchanges. Human and bovine bone did not have significantly different properties. The storage capability of cortical bone was generally lower than that of cancellous bone. Tobramycin concentrations were significantly lower in the initial phase; however, it eluted more steadily and over a longer period, so that from day 6 onwards, its concentration was greater than that of vancomycin. After 28 days, the tobramycin concentration was 18.09 +/- 2.46 mg/L (bovine cancellous bone). In conclusion, bone, if processed adequately, is an excellent carrier for vancomycin and tobramycin. Cortical bone is as suitable as cancellous bone. The pharmacokinetics of human and bovine bone are comparable. Using an antibiotic-graft compound, eradication of pathogens and grafting of bony defects may be accomplished in a one-stage procedure.
authors.affiliation: Department of Orthopaedics and Central Bone Bank Vienna, Department of Infection Control, Danube Hospital, Langobardenstrasse 122, 1220 Vienna. hienzwinkler@compuserve.com
authors.forename: H
authors.initials: H
authors.lastname: Winkler
authors.forename: O
authors.initials: O
authors.lastname: Janata
authors.forename: C
authors.initials: C
authors.lastname: Berger
authors.forename: W
authors.initials: W
authors.lastname: Wein
authors.forename: A
authors.initials: A
authors.lastname: Georgopoulos
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016025:Bone Transplantation; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D002417:Cattle; D005612:Freeze Drying; D006801:Humans; D014031:Tobramycin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014640:Vancomycin / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin; D014031:Tobramycin