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Addition of Antibiotics to Cement

 - See: Infection Menu and Wound Management: and Local Antibiotic Delivery for Septic Joints

- Discussion:
  - basic science:
useful in treating biofilm;
       - references:
             - In vitro characteristics of tobramycin-PMMA beads: compressive strength and leaching.   
             - Antibiotic bone cement in THA. An in vivo comparison of the elution properties of tobramycin and vancomycin
             - Long-term elution of antibiotics from bone-cement: an in vivo study using the prosthesis of antibiotic-loaded acrylic cement 
             - High concentration and bioactivity of vancomycin and aztreonam eluted from Simplex cement spacers in two-stage revision of infected hip implants: a study of 46 patients at an average follow-up of 107 days.

  - complications and safety issues:

              - in the report by Springer, et al total antiobiotic load of 10.5 g of vanc and 12.5 g of gent was clinically safe, w/ no evidence of
                     acute renal insufficiency or other systemic side effects;
              - in the report by van Raaij, et al, authors note a case of renal failure with 2 gm of gent (serum levels of gent were high);
      - references: 
              - Systemic safety of high-dose antibiotic-loaded cement spacers after resection of an infected total knee arthroplasty.
              - Acute renal failure after local gentamicin treatment in an infected total knee arthroplasty. 
              - Audiometric thresholds in osteomyelitis patients treated with gentamicin-impregnated methylmethacrylate beads (Septopal).
              - Acute renal failure associated with vancomycin- and tobramycin-laden cement in total hip arthroplasty.

- Antiobiotic Bead Pouch: (addition of antibiotics to cement) (see OM and post traumatic tibial OM

- Technical Considerations for Joint Replacement:
StageOne™ Knee Cement Spacer Molds
            - StageOne™ Hip Cement Spacer Molds
            - references:
                    - Successful treatment of total hip and knee infection with articulating antibiotic components: a modified treatment method. 

- Characteristics of Individual Antibiotics:
    - note that lincomycin, tetracycline, and rifampin should not be added to methylmethacrylate;
    - note: the antibiotics must be added to the cement in a powered form (which may or may not be available from the pharmacy);
    - addition of antibiotics to cement during arthroplasty will not interfere with mechanical properties if the amount of antibiotics
             is kept less than 2.5 gm per 40 grams; 
    - Gentamicin and Tobramycin Properties in Cement
    - Vancomycin properties in Cement:
ref: Increasing the Elution of Vancomycin from High-Dose Antibiotic-Loaded Bone Cement: A Novel Preparation Technique

    - Erythromycin:
           - 1 gm of erythromycin per 40 gm packet of cement;
           - has good bacterial spectrum, rarely causes allergies, and has good elution from cement;
    - Clindamycin
           - Biomet premixed cement
           - Refobacin 
           - Biomet cementing university
           - Copal Bone Cement Is More Effective in Preventing Biofilm Formation than Palacos R-G
           - [Elution kinetics and antimicrobial effects of gentamicin- and clindamycin-loaded bone cements in vitro]
           - Treatment of contaminated bone defects with clindamycin-reconstituted bone xenograft-composites
           - Comparison of cortical bone and serum concentrations of clindamycin achievable by direct local infusion and intravenous administration
           - Methylmethacrylate as a Space Maintainer in Mandibular Reconstruction
           - The effects of clindamycin on human osteoblasts in vitro
    - Daptomycin:
ref: Characterization of Daptomycin-loaded Antibiotic Cement
    - Cipro
In vitro elution of ciprofloxacin from polymethylmethacrylate cement beads

- Protocols for Addition for Antibiotics to Cement: 
    - in the study by Koo, et al., 21 of 22 patients were sucessfully treated with staged revision using 2 g each of vanc, gent, and
           cefotaxime per 40 g of cement; 
    - in the study by Masri, et al, the authors conclude that at least 3.6 g of tobra and 1 g of vanc per package of bone-cement is
           recommended in 2-stage exchange arthroplasty for infected total hip and knee arthroplasties; 
           - there was significant increase in elution of vanc when dose of tobra was increased from at most 2.4 g to at least 3.6 g; 
    - Evans, et al, the authors used 4 g of vanc and 4.6 g of tobra per 40 gm batch of cement in 54 periprosthetic joint infections; 
           - at 2 year follow up there were no no renal, vestibular, or hearing changes; 
    - dosing and biomechanical strength considerations: 
           - addition more than 4.5 g of powder substantially weakens bone cement; 
           - approx 8 grams of antibiotic powder per 40 gm of cement is the highest amount that can be added; 
           - antibiotics added in liquid form dramatically decrease strength characteristics; 
           - references:
                - Two-stage revision THA for infection with a custom-made, antibiotic-loaded, cement prosthesis as an interim spacer. 
                - Impregnation of vancomycin, gentamicin, and cefotaxime in a cement spacer for two-stage cementless reconstruction in infected total hip arthroplasty
                - Long-term elution of antibiotics from bone-cement: an in vivo study using the prosthesis of antibiotic-cement 
                - Successful treatment of total hip and knee infection with articulating antibiotic components: a modified treatment method. 
    - mixing protocol: 
           - cement liquid and powder is mixed together first, and then antibiotic powder is added; 
           - this leaves as many large crystals intact as possible to create a more porous mixture to increase antibiotic elution rate; 
           - antibiotics must be added to the cement in a powered form (which may or may not be available from the pharmacy); 
           - vacuum-mixing is not used: decreases the porosity of the cement, which also decreases rate of elution of the antibiotics; 
           - reference:
                    - Practical applications of antibiotic-loaded bone cement for treatment of infected joint replacements. 
                    - Volume and surface area study of tobramycin-polymethylmethacrylate beads.
    - palacos cement: 
           - superior ATB elution characteristics for treating osteomyelitis
           - higher porosity allows for improved elution characteristics but may make it less amenable to modern cementing techniques;
           - when mixing the cement it is important not decrease the porosity of the cement by not using the vacuum pump;
           - temporary spacer: 
                  - tobramycin: add 2.4 to 3.6 grams per 40 gm package of cement; 
                  - vancomycin: add 1-4 grams per 40 grams of cement; 
    - simplex-p bone cement 
           - loaded w/ antibiotics (0.6 to 2.4 grams of tobramycin & 0.5 to 1.0 gram of vancomycin per forty grams of cement) 
           - has superior handling characteristics; 
           - amount of ATB that can be added to Simplex Cement (40 gm/pack); 
                  - cefazolin: 6.0 gm (may be heat labile?) 
                  - tobramycin: 9.6 gm 
                  - vancomycin: 5.0 gm 
                 - based on allowed volume (24 cc ATB / 120 cc cement)

- References:
      - Antibiotic-Impregnated Cement and Beads for Orthopedic Infections
      - A prospective, randomized clinical trial comparing an antibiotic-impregnated bioabsorbable bone substitute with standard antibiotic-impregnated cement beads in the treatment of chronic osteomyelitis and infected nonunion.
      - Sufficient Release of Antibiotic by a Spacer 6 Weeks after Implantation in Two-stage Revision of Infected Hip Prostheses 
      - Vacuum-Mixing Significantly Changes Antibiotic Elution Characteristics of Available Antibiotic-Impregnated Bone Cements
      - Local Antibiotic Therapy in the Treatment of Bone and Soft Tissue Infections 
      - Elution of gentamicin and vancomycin from polymethylmethacrylate beads and hip spacers in vivo
      - Complications after spacer implantation in the treatment of hip joint infections

The In Vitro Elution Characteristics of Antifungal-loaded PMMA Bone Cement and Calcium Sulfate Bone Substitute

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