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Assessment of cefazolin and cefuroxime tissue penetration by using a continuous intravenous infusion.

Author(s): Connors JE, DiPiro JT, Hayter RG, Hooker KD, Stanfield JA, Young TR

Affiliation(s): University of Georgia College of Pharmacy, Augusta.

Publication date & source: 1990-06, Antimicrob Agents Chemother., 34(6):1128-31.

Publication type: Clinical Trial; Randomized Controlled Trial

A continuous intravenous infusion was used to assess the tissue penetration of cefazolin (14 subjects) and cefuroxime (15 subjects) in orthopedic surgery patients. Subjects were randomly assigned to receive a continuous intravenous infusion of cefazolin (mean, 178.6 mg/h) or cefuroxime (mean, 330.0 mg/h) at a rate estimated to achieve a target steady-state total concentration of 50 micrograms/ml in serum. The infusion was initiated 12 to 14 h before surgery, and blood and muscle tissue samples were collected intraoperatively at the times of incision and wound closure. Although there was a significant difference between the free concentrations of cefazolin (at incision, 9.3 micrograms/ml; at closure, 9.2 micrograms/ml) and cefuroxime in serum (at incision, 26.9 micrograms/ml; at closure, 31.8 micrograms/ml), there was no difference in the total concentrations in muscle at either surgical incision (cefazolin, 6.1 micrograms/g; cefuroxime, 5.6 micrograms/g) or wound closure (cefazolin, 7.7 micrograms/g; cefuroxime, 7.4 micrograms/g). There was a significant correlation between the pooled free serum and total muscle concentrations for cefazolin (P = 0.001); however, there was no correlation between these variables with the pooled cefuroxime data (P = 0.403). These findings indicate that the free drug concentration in serum alone is not consistently predictive of the total concentration of cephalosporin in muscle.

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