Target site concentrations after continuous infusion and bolus injection of cefpirome to healthy volunteers

Background: Recent data indicate a higher level of effectivity of beta-lact am antibiotics if serum concentrations are kept above the minimal inhibitor y concentration (MIC) of the pathogen. This concept would favor continuous infusion over bolus dosing. However, it is usually not the serum concentrat ion but the free interstitial concentration in the target tissue that deter mines antibiotic activity. We therefore set out to measure effective drug c oncentrations in the interstitial space of muscle and subcutaneous adipose tissue and to compare trough levels and times above the MIC after bolus ver sus continuous infusion of cefpirome. Methods: Twelve healthy volunteers received a single dose of 2 g cefpirome as an intravenous bolus or as a continuous infusion over 8 hours in a cross over design, and the resulting free interstitial tissue concentrations were measured with use of microdialysis. Results: After bolus injection, mean interstitial trough concentrations wer e 3.0 +/- 1.9 mu g/mL and 2.1 +/- 1.0 mu g/mL for muscle and subcutaneous t issue, respectively; continuous infusion resulted in trough levels of 10.1 +/- 6.8 mu g/mL and 10.1 +/- 4.6 mu g/mL for muscle and subcutaneous tissue , respectively. This resulted in significantly longer times above the MIC w ith continuous infusion for Straphylococcus epidermidis and Enterobacter cl oacae. Bacteria with an MIC less than or equal to 1 would be covered by eit her method, whereas higher doses seem to be necessary for Pseudomonas aerug inosa. Conclusion: Although susceptible organisms will usually be covered sufficie ntly with standard dosing regimens, soft tissue infections with bacteria th at have MIC values of 2 to 8 may profit from continuous application. Covera ge of P aeruginosa, however, would be inadequate with conventional daily do ses of 4 g cefpirome regardless of the method of application.