PENETRATION OF PARENTERALLY ADMINISTERED CEFTIOFUR INTO STERILE VS PASTEURELLA HAEMOLYTICA-INFECTED TISSUE CHAMBERS IN CATTLE

The effect of bacterial infection on antibiotic activity and penetrati on of parenterally administered ceftiofur into implanted tissue chambe rs was studied in cattle. Tissue chambers were implanted subcutaneousl y in the paralumbar fossae of eight calves (256-290 kg body weight). A pproximately 80 days after implantation, the two chambers on one side of each animal were inoculated with Pasteurella haemolytica (10(6) CFU /chamber). Eighteen hours after inoculation, ceftiofur sodium was admi nistered intravenously (5 mg/kg) to each of the calves. Non-infected c hamber fluid, infected chamber fluid and heparinized blood samples wer e collected immediately before and at 1, 3, 6, 12 and 24 h after drug administration. Concentrations of ceftiofur and desfuroylceftiofur met abolites and ceftiofur-equivalent microbiological activity were measur ed by high-pressure liquid chromatography and microbiological assay re spectively. Concentrations of ceftiofur and desfuroylceftiofur metabol ites and antimicrobial activity in P. haemolytica-infected tissue cham bers were significantly higher than those in non-infected tissue chamb ers at all sampling times, indicating that ceftiofur, regardless of th e method used for analysis, localizes at higher concentrations at tiss ue sites infected with P. haemolytica. Antibiotic activity-concentrati on ratios were lower in plasma and infected chamber fluid compared wit h non-infected chamber fluid, suggesting that antibiotic was bound to proteins. However, higher antimicrobial activity in the infected chamb er fluid compared with the non-infected chamber fluid suggests that ac tive drug is reversibly bound to proteins. Protein-bound desfuroylceft iofur may represent a reservoir for release of active drug at the site of infection In the animal.