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IN VITRO ELUTION CHARACTERISTICS OF GENTAMICIN AND VANCOMYCIN COMBINED IN ACRYLIC BONE-CEMENT



Abstract

Introduction: The use of polymethylmethacrylate (PMMA) bone cement loaded with antibiotics has become increasingly common in the treatment of infected knee and hip arthroplasties and also as prophylaxis in primary joint replacement. However bacterial resistance in antibiotics is an increasing and emerging problem. PMMA bone cements containing different antibiotics, such as gentamicin plus vancomycin may be effective in prevention and treatment of infections (particularly from MRSA and MRSE). The purpose of this study was to determine the in vitro elution characteristics of gentamicin and van-comycin when combined in acrylic cement.

Material and methods: Three groups of six cement disks were prepared. Group I (control group) contained 0.5g of gentamicin sulphate per 40-g packet of Palacos-R+G powder. Group II contained 0.5g of gentamicin sulphate and 1g of finely powdered vancomycin and Group III contained 0.5g of gentamicin sulphate and aqueous solution of vancomycin (containing 2mL water for injection and 1g vancomycin). All discs were prepared using vacuum mixing technique. Each cement disc (25mm diameter × 20mm thick) was fully immersed in a 50-mL bath of normal saline at 37o C temperature in a covered beaker. At specific sampling intervals (1, 3, 7, 15, 30, 60, 90, 120, 150, 180 days) the discs were removed and placed in fresh 50 ml bath for 24 hours. Then a 2 mL sample of each solution was taken. Samples were frozen at −60° C until they were analyzed. Gentamicin and vancomycin concentrations were measured using fluorescence polarization immunoassay.

Results: With regards to gentamicin release, high but rapidly decreasing antibiotic levels were detected within the first week, resulting in an almost steadily low concentration by the end of the first month. Cement samples eluted significantly more gentamicin (120%-20% during the first month) when powdered vancomycin (Group II) was added. The influence on the gentamicin release was significant but minor when aqueous solution of vancomycin (Group III) was added (40%-20% during the same period).

With regards to vancomycin release, high antibiotic levels were detected within the first 3 days and low concentrations after the first week. Cement samples from Group II eluted significantly more antibiotic (80%–100%) in comparison with samples from Group III during the first days.

Gentamicin and vancomycin are detectable in measurements at 150 and 180 days samples.

Conclusions: Bone cements loaded with combinations of gentamicin and vancomycin are more effective in releasing gentamicin than bone cements with gentamicin as a single drug. The presence of powdered vancomycin in cement samples has major influence on the total gen-tamicin release in comparison with cements containing aqueous solution of vancomycin.

Correspondence should be addressed to Ms Larissa Welti, Scientific Secretary, EFORT Central Office, Technoparkstrasse 1, CH-8005 Zürich, Switzerland