A COMPARISON OF THE PENETRATION OF CEFUROXIME AND CEPHAMANDOLE INTO BONE, FAT AND HEMATOMA FLUID IN PATIENTS UNDERGOING TOTAL HIP-REPLACEMENT

Twelve patients undergoing total hip anthroplasty received, at the ind uction of anaesthesia, cephamandole (1 g) and cefuroxime (1.5 g); furt her doses of cephamandole (1 g) and cefuroxime (750 mg) were given at 8 and 16 h after the operation. Routine total hip arthroplasty was per formed and at timed intervals during operation samples of bone, fat an d blood were collected for assay for HPLC analysis. Samples of the hae matoma fluid that formed around the operation site and further blood s amples were also collected at 7 and 15 h after the operation. Although considerable variation was observed in the bone and fat concentration s of both agents, the cefuroxime levers were substantially higher than those of cephamandole, with mean values for bone of cefuroxime 36.0 m g/L (95% CI 29.0-43.0 mg/L) and cephamandole 18.3 mg/L (95% CI 14.2-22 .4 mg/L) and for fat of cefuroxime 15.0 mg/L (95% CI 11.1-18.9 mg/L) a nd cephamandole 11.2 mg/L (95% CI 7.2-15.2 mg/L). When corrected for b lood concentrations the penetration of both agents was similar (bone, 43.6% cefuroxime and 37.8% cephamandole; fat, 16.0% cefuroxime and 19. 2% cephamandole). Cefuroxime concentrations in haematoma drain fluid w ere higher than those of cephamandole 6-8 h after the operation (17.8 versus 8.3 mg/L) but lower at 14-16 h (7.7 versus 9.6 mg/L). We conclu de that there are no significant differences between the bone, fat or haematoma penetration of cefuroxime and cephamandole and that any diff erences in the absolute levels of the two agents are due to difference s in the total drug administered rather than their ability to penetrat e into these sites. Time-kill curves for cefuroxime and cephamandole a gainst five clinical isolates of Staphylococcus aureus failed to ident ify any significant differences between the rates of kill for the two agents at the concentrations seen in bone, fat or haematoma fluid. For both prophylaxis regimens antibiotic concentrations exceeded the MICs for potential pathogens for the duration of the operation and also in the haematoma which surrounds the operation site for up to 24 h after the operation.