Journal of Antimicrobial Chemotherapy, Vol 40, 99-104, Copyright © 1997 by The British Society for Antimicrobial Chemotherapy
AM Lovering, J Perez, KE Bowker, DS Reeves, AP MacGowan and G Bannister
Twelve patients undergoing total hip anthroplasty received, at the
induction of anaesthesia, cephamandole (1 g) and cefuroxime (1.5 g);
further doses of cephamandole (1 g) and cefuroxime (750 mg) were given at 8
and 16 h after the operation. Routine total hip arthroplasty was performed
and at timed intervals during operation samples of bone, fat and blood were
collected for assay for HPLC analysis. Samples of the haematoma fluid that
formed around the operation site and further blood samples were also
collected at 7 and 15 h after the operation. Although considerable
variation was observed in the bone and fat concentrations of both agents,
the cefuroxime levels were substantially higher than those of cephamandole,
with mean values for bone of cefuroxime 36.0 mg/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) and cephamandole 11.2 mg/L
(95% CI 7.2-15.2 mg/L). When corrected for blood 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 were 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 conclude that there are no significant
differences between the bone, fat or haematoma penetration of cefuroxime
and cephamandole and that any differences in the absolute levels of the two
agents are due to differences in the total drug administered rather than
their ability to penetrate into these sites. Time-kill curves for
cefuroxime and cephamandole against five clinical isolates of
Staphylococcus aureus failed to identify 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.
ORIGINAL ARTICLES
A comparison of the penetration of cefuroxime and cephamandole into bone, fat and haematoma fluid in patients undergoing total hip replacement
Bristol Centre for Antimicrobial Research and Evaluation, Department of Medical Microbiology, Southmead Hospital, UK.
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