Am. Lovering et al., A COMPARISON OF THE PENETRATION OF CEFUROXIME AND CEPHAMANDOLE INTO BONE, FAT AND HEMATOMA FLUID IN PATIENTS UNDERGOING TOTAL HIP-REPLACEMENT, Journal of antimicrobial chemotherapy, 40(1), 1997, pp. 99-104
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.