Percentages of free and protein-bound cefazolin and cephaloridine in serum and interstitial fluid of dogs were determined by ultrafiltration and microbiologic assay. The percentages of cephaloridine and cefazolin bound to protein in serum were 10% and 80%, respectively. In interstitial fluid accumulating within tissue-embedded polypropylene capsules, 29% of cefazolin was bound to protein, and cephaloridine was unbound. Both antibiotics rapidly penetrated the interstitial fluid and attained measurable levels 5 min after intravenous administration. Levels of total cefazolin in the interstitial fluid were generally higher than those of cephaloridine; however, concentrations of free cephaloridine in the fluid exceeded the levels of free cefazolin after the first 15 min. Binding of anitbiotics by serum proteins does not restrict such agents to the intravascular space, since a highly protein-bound compound has been shown to penetrate interstitial fluid as readily as one that is minimally bound. It should be noted, however, that this penetration may be due primarily to the slow rate of binding of cefazolin to serum proteins.
The kinetics of the migration of intestinal bacterial flora to the peritoneal cavity upon death of the host was studied. A laboratory experiment that excluded any source of contamination was used. Samples of sterile saline solution in which a loop of the intestine was submerged were streaked onto blood agar at given intervals. Recovery of bacteria began after about 15 hours, with Staphylococcus aureus being the predominant organism. This organism showed a gradual decrease through a 36-hour period and at 48 hours was almost absent. In the same manner, other organisms such as gram-negative bacilli and spore-forming gram-positive bacilli gradually increased in numbers.
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