Fluid Penetration into Antimicrobial Loaded Bone Cement is a Good Indicator for Antimicrobial Release.

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Authors: Klempf P, McLaren A, Casteneda P, McLemore R.
Banner Good Samaritan Medical Center, Phoenix, AZ

Title: Fluid Penetration into Antimicrobial Loaded Bone Cement is a Good Indicator for Antimicrobial Release.

Background: Antimicrobial loaded bone cement (ALBC) delivers antimicrobials to orthopaedic infections. Fluid penetration of ALBC can be measured quantitatively. Release is controlled by Washburn kinetics with pressure as a determining factor. In vitro elution studies have been performed under atmospheric conditions. In vivo release occurs under interstitial pressures that are higher than atmospheric, as high as post capillary venual pressure.

Hypothesis/Purpose: Is drug release from ALBC quantitatively related to fluid penetration into ALBC? Does hydrostatic pressure effect fluid penetration?

Methods: ALBC was formulated as high-dose with 10g gentamicin or low-dose 1g gentamicin per batch of Simplex P. Test specimens were fabricated by pressing ALBC in dough-phase between clear styrene sheets (4cmx1cm) to a thickness of 1 mm. Edges were machined at low speed. A single batch was made for each treatment.
3 test specimens for each treatment were immersed in 5 mg/mL aqueous green dye in a 1-inch column of H20 or 16-inch column of H20 respectively for 28 days. Penetration was documented on high definition digital photographically on days 1,3,5,7,14,21, and 28. Fluid penetration was visualized as an advancing front of green color and quantified using a Matlab algorithm.

3 test specimens from each treatment were immersed into phosphate buffered saline with total eluant exchanges on day 1, 3, 5, 7, 14, 21, 28 to achieve infinite sink conditions over 28 days. Total released gentamicin was determined using ninhydrin color spectrometry.
Data were analyzed with ANOVA, t-test, or correlation.

Results: Fluid penetration and elution was much greater for 10g samples in 16in. (0.7+0.05 mm) of fluid than for samples in 1in. of fluid (0.48+0.08 mm) at 28 days (p=0.02) (Fig 1). High-dose ALBC with 1in pressure has 6-fold greater fluid penetration (0.48+0.08 mm) than low-dose ALBC (0.07+0.005 mm). The greatest drug release is in the first 24 hours. The greatest elution time point matches the greatest fluid penetration time point (Day 1).

Discussion: Quantitative measurement of fluid penetration into ALBC has been improved. Fluid Penetration matches antimicrobial release behavior. Pressure changes fluid penetration. Hydrostatic pressure should be considered when interpreting in vitro data.

Conclusion: Fluid penetration into ALBC is an indicator of antimicrobial release. Pressure has an important effect on fluid penetration and elution from ALBC.

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