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IN VIVO RELEASE OF HIGH DOSE VANCOMYCIN FROM LOADED CEMENT IN PATIENTS WITH PERIPROSTHESES INFECTION: EFFECTIVE BACTERICIDAL ACTIVITY



Abstract

Deep periprostheses infection is a devastating complication that occurred in 8 to 20% of patients treated by en bloc resection and prosthetic reconstruction for bone sarcomas.

The systemic safety of high dose vancomycin loaded spacer has been investigated but rarely the elution of vancomycin in vivo. The aim of the study is to evaluate the elution of vancomycin into the site of the excision arthroplasty to see if effective bactericidal activity can be obtained.

Patients and Methods: From 2006 to 2008, 16 consecutive patients were managed by prosthetic exchange procedure using high dose vancomycin loaded cement. Patients were males :7, females :9. Average of age at the time of surgery was 22 years.

Antibiotic-loaded methylmethacrylate cement beads were prepared by adding 4 g of vancomycin powder to a 40 g pack of Palacos R cement in the operative place immediately before the operation. We used 4 G vancomycin per batch of 40 G cement and generally used 2 to 4 batches of cement in one spacer depending of the size and length of resection. The average dose of vancomycin was 7.5 G (4–14.5).

The wounds were closed with absorbable mono-filaments sutures over one suction drain.

Intravenous antibiotics excluding vancomycin were given for 6 to 24 weeks.

Patients biological values and the concentrations of vancomycin in the blood and in the aliquots of suction drainage were checked daily until removal of drain. Vancomycin was measured by fluorescent polarization immunoassay on the AxSYM analyzer (Abbott).

Results: the serum concentration of vancomycin remained in all patients under 2 μg/ml confirming the systemic safety of the method. Local concentration of vancomycin depended of the dose of vancomycin used and decreased quickly during the first week: half life :2.25 days. For a dose of 10 G vancomycin, the average concentration in the liquid from the drain was :

  • d1 :725μg/ml

  • d2 :510 μg/ml

  • d3 :346 μg/ml

on day 10, its remained over 35μg/ml vancomycin in the aliquot of the drain

These results should be compared to the bactericidal concentration of vancomycin for staphylococcus aureus:10 to 20 μg/ml for usual organisms, 20 to 40 for resistant organisms.

We had no reported cases of allergy, toxicity or intolerance.

Conclusion : high dose vancomycin spacers result in very low serum concentration without risk of systemic toxicity. In the operative wound, very high concentration are obtained, 10 to 20 fold bactericidal concentration for staphylococcus aureus.

Additional studies are needed, with longer follow-up to evaluate the clinical efficacy of this method.

Correspondence should be addressed to: EFORT Central Office, Technoparkstrasse 1, CH – 8005 Zürich, Switzerland. Email: office@efort.org