Impact of different methodologies on the estimation of antibiotic tissue penetration: Determination of cefmetazole penetration into bone and soft tissue

The percent penetration and estimation of extracellular fluid concentration of cefmetazole in bone and soft tissue was determined in patients undergoing total knee arthroplasty. Simultaneous serum, soft tissue, and bone samples were obtained at regular intervals during surgery and analyzed for cefmetazole content by high performance liquid chromatography. Percent penetration was calculated based on the calculated free concentration and area under the concentration-time curve (AUC). Extracellular fluid concentrations were estimated by two methods, an equilibrium method assuming equal free (unbound) serum concentrations and free extracellular fluid concentration and a weight method based on approximate percentage of total tissue weight comprised by extracellular fluid. The AUC and percent penetration in bone calculated using a bone standard curve were significantly higher than by using a phosphate buffer standard curve (AUC p = 0.0012, % penetration p = 0.0001). The extracellular fluid concentration, estimated by either of the methods listed above, was significantly higher than the tissue homogenate for both soft tissue and bone (p = 0.0001). Therefore, if the distribution of antibiotic within the tissue is not taken into account, soft tissue and bone concentrations of cefmetazole would be under-estimated by 3- 5 fold. Investigators and clinicians need to be cognizant of these problems and avoid misinterpretation of tissue penetration studies.