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Vancomycin Properties in Ca Sulfate and Bone Graft

Discussion:
     - vancomycin and addition of antibiotics to cement,  and local delivery of antibiotics to infected joints):
     - calcium sulfate:
              - biologically inert osteoconductive material which serves as a temporary scaffold for osteoblasts;
              - osteoset (wright medical technology):
              - typically dissolves in one to two months; 
     - vancomycin: local pharmokinetics vs systemic:
              - has much slower and more consitent elution characteristics than tobramycin and gent; 
              - vancomycin shows very poor tissue penetration, which is a disadvantage of IV infusion;
              - in contrast, w/ local application there will also be reduced penetration from the implanted site into the vascular system,
                          which keeps local tissue levels high and systemic levels low;
     - safety:
              - vancomycin shows the least cytotoxic effect of all commonly used antibiotics and is not likely to cause systemic side effects
                         after local application;
      - bactericidal activity and biofilm:
              - vancomycin is one of the antibiotics with intracellular bactericidal activity and therefore should cover small colony variants
                         of staphylococci and MRSA;
              - penetrates glycocalices very rapidly;
              - once incorporated in biofilm Vancomycin shows a strain dependent bactericidal biofilm activity between 8 times and 128
                        times the MIC of planktonic bacteria;
              - shows superior bactericidal activity against biofilm embedded staphylococci and MRSA compared with most other
                        antibiotics;
              - references:
                    - Impact of biofilm on activity of vancomycin alone and in combination with tigecycline and rifampicin against Staph.
                    - Comparison of biofilm-associated cell survival following in vitro exposure of MRSA biofilms to the antibiotics

- Elution Characteristics:

      - references:
              - The levels of vancomycin in the blood and the wound after the local treatment of bone and soft-tissue infection with antibiotic-loaded calcium sulphate as carrier material
              - The in vitro elution characteristics of vancomycin from calcium phosphate-calcium sulfate.
              - Local release of antibiotics for surgical site infection management using high-purity Ca sulfate: an in vitro elution study.
              - Size and composition of synthetic calcium sulfate beads influence dissolution and elution rates in vitro.
              - The in vitro elution characteristics of vancomycin from calcium phosphate-calcium sulfate beads
              - Preliminary in vitro evaluation of therapy for wound infection reduction: rapidly resorbing local antibiotic delivery.
              - Antibiotic-loaded Ca sulfate beads for prevention of colonization and biofilm formation in periprosthetic infections.
              - Effects of bead size and polymerization in PMMA bone cement on vancomycin release.

 - General References:
         - Calcium sulfates: what is the evidence?
         - The Use of Calcium Sulfate Impregnated with Vanc in Treatment of Open Fractures of Long Bones: A Preliminary Study.
         - The use of a biodegradable antibiotic-loaded calcium sulphate carrier containing tobramycin for the treatment of chronic osteomyelitis: a series of 195 cases.
         - Calcium Sulfate- and Calcium Phosphate-Based Bone Substitutes. Mimicry of the Mineral Phase of Bone
         - 50 Years ago in CORR: The use of plaster of Paris to fill defects in bone Leonard F. Peltier, MD CORR 1961;21:1-31.

- References from Addition of Vancomycin to Bone Grafts: (see osteomyelitis and bone grafts)
      - High active local levels of vancomycin without nephrotoxicity released from impacted bone allografts in 20 revision hip arthroplasties.
      - Vancomycin-supplemented cancellous bone allografts in hip revision surgery.
      - Results of vancomycin-impregnated cancellous bone grafting for infected tibial nonunion.
      - Cancellous bone as an antibiotic carrier
      - Vancomycin-supplemented impacted bone allografts in infected hip arthroplasty. Two-stage revision results. 
      - Histology of vancomycin-supplemented impacted bone allografts in revision total hip arthroplasty
      - Antibiotic-autogenic cancellous grafting is an effective method for management of infected tibial defects: a comparison study.
      - Results of vancomycin-impregnated cancellous bone grafting for infected tibial nonunion.
      - In vitro release of vancomycin and tobramycin from impregnated human and bovine bone grafts.