Pharmacokinetics of fusidic acid and cefepime in heart tissues: implications for a role in surgical prophylaxis.
The pharmacokinetic profiles of fusidic acid and cefepime in heart tissues were assessed in 30 patients undergoing elective valve replacement and cardiopulmonary bypass. Single doses of 1 g of fusidic acid and 2 g of cefepime were administered intravenously to two groups of 15 and 15 patients respectively upon initiation of anesthesia. Samples of serum, heart valves, myocardium, pericardium, mediastinal fat and sternum were collected within <1 hour, 1-2 h and 2-4 h after the end of drug infusion. Drug concentrations were estimated by a microbiological assay. It was found that concentrations of fusidic acid in all specimens were 20-fold higher than the MIC90s of methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis, being at such levels throughout all period of sampling. Cefepime concentrations in heart valves collected 1-2 h after drug infusion were higher than the MIC90s of multidrug-resistant Enterobacteriaceae. It is concluded that both fusidic acid and cefepime penetrated heart tissues adequately; however only fusidic acid could also accumulate in the mediastinum. These data suggest that both antibiotics may be a good alternative for prophylaxis in open heart surgery.
Kanellakopoulou
K
K
4th Department of Internal Medicine, University of Athens, Medical School, Greece.
Tselikos
D
D
Giannitsioti
E
E
Giamarellos-Bourboulis
E J
EJ
Apostolakis
E
E
Lolas
C
C
Giamarellou
H
H
D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D019072:Antibiotic Prophylaxis; D002315:Cardiopulmonary Bypass; D000077723:Cefepime; D002511:Cephalosporins / Q000493:pharmacokinetics*; D005260:Female; D005672:Fusidic Acid / Q000493:pharmacokinetics*; D019918:Heart Valve Prosthesis Implantation; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D009206:Myocardium / Q000378:metabolism*; D013211:Staphylococcus aureus; D013212:Staphylococcus epidermidis; D014018:Tissue Distribution
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D005672:Fusidic Acid; D000077723:Cefepime