Tissue distribution of beta-lactam antibiotics. Experimental studies in rabbits

Tissue distribution of ampicillin, dicloxacillin and cefuroxime was studied in rabbits. Different methods allowing frequent samples to be obtained from the same animal were used. Tissue fluid was obtained from subcutaneously implanted steel net cages and by implantation of thin cotton threads under the muscle fascia. A microtechnique was developed for determination of antibiotic concentrations in small muscle samples. The concentration time course in serum and tissue was followed after a single intravenous or intramuscular injection of the antibiotic. In tissue cage fluid, levels of ampicillin and dicloxacillin were low as compared to the serum concentrations. Also, maximum levels occurred later than in serum and elimination was slower. In contrast, rapid peak levels were achieved in muscle tissue with all three investigated antibiotics and the muscle concentrations declined parallel to the serum levels. The results also indicated that beta-lactam antibiotics are not homogeneously distributed in muscle tissue but mainly confined to the extracellular fluid volume. Whole tissue levels could therefore underestimate the actual antibiotic concentrations in the tissue fluid where the bacteria causing soft tissue infections are most likely to be found. Serum levels, however, seemed to be a good indicator for the concentration time course in tissue fluid.