In vivo release of high dose vancomycin from

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In vivo release of high dose vancomycin from
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In vivo release of high dose vancomycin from loaded cement in patients with periprostheses infection effective bactericidal activity - 10th EFORT Congress, 3-6 June 2009 Vienna et Séminaire du Groupe ethique et médicament du 13 juin au Centre Hospitalier Universitaire Raymond Poincaré

Delepine, N.; Alvarez, J.; Abe, E.;; Markowska, B.;; Delepine, G.;

After limb salvage, infection

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

• Resulting often in secondary amputation

Antibiotic loaded cement spacers

• Have been widely used since 1972 to prevent and to treat prosthetic infection

• The delivery of a high concentration of antibiotics in a localized area is thought to be safer than systemic administration of intravenous antibiotics in such doses

the emergence of increased resistance of staphylococcus

• Explains recent less effectiveness of conventionnal antibiotic loaded cement (low dose of antibiotics)

• Plaes for higher doses of antibiotics

• and compells us to consider the antibiotic concentration in the operating field

systemic safety of high dose vancomycin

• The systemic safety of high dose vancomycin loaded spacer has been investigated* but rarely the elution of high vancomycin from cement in vivo.

*Systemic Safety of High-Dose Antibiotic-Loaded Cement

Spacers after Resection of an Infected Total Knee Arthroplasty Bryan D. Springer, MD and coll Clin. Orthop.Rel.Desease 2004

The aims of the study

1°)To confirm the systemic safety of using high doses of vancomycin in cement

2°)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 2 stages procedure using high dose vancomycin loaded cement spacer.

• Patients were males :7 females : 9. Average of age at the time of surgery was 22 years.

Antibiotic-loaded methylmethacrylate cement

• Cement were prepared by adding 4 g of vancomycin powder to a 40 g pack of Palacos R cement in the operative room during the operation.

Antibiotic-loaded methylmethacrylate cement

• We generally used 2 to 4 batches of cement in one spacer depending of the size and length of resection

• The average dose of implanted vancomycin was 7.5 G (4-14.5).

spacer for proximal tibia

The spacer was composed of metallic rods covered with antibiotic loaded cement


Vancomycine (4 gr/pack).

spacers for femur

other spacers

Spacers used for proximal humerus or acetabular prosthesis

Post operative cares

• 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 (d10-d15).

Results for systemic safety

• The serum concentration of vancomycin remained under 2 µg/ml in all patients

• We observed no case of

– allergy,

– toxicity

– or intolerance

Local concentration

• Local concentration of vancomycin depended of the dose of vancomycin used and decreased quickly during the first week

• half life :2.25 days.

Local concentration for 10 Grams

• For a dose of 10 G vancomycin , the average concentration from the drain was :d1 :725µg/ml, d2 :510 µg/ ml,d3 :346

Is it bactericidal?

• 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 µg/ml for resistant organisms .


• 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.

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