Concentrations in plasma and tissue penetration of ceftriaxone and ornidazole during liver transplantation

Abstract

Plasma and epiploic fat drug concentrations and fat penetration of ceftriaxone and ornidazole given for antimicrobial prophylaxis were studied in 11 patients scheduled for liver transplantation. Ceftriaxone (1 g) and ornidazole (500 mg) were infused during 30 min after the induction of anesthesia. Arterial blood and epiploic fat samples were collected at 30, 60, and 120 min and then every 90 min following the end of the infusion until closure of the peritoneum. Blood samples were immediately centrifuged, and plasma and fat were stored at -35 degrees C until analysis. Ceftriaxone and ornidazole concentrations were determined by high-performance liquid chromatography. Surgery lasted 440 +/- 84 min and required a mean of 9.5 units of packed erythrocytes and 13 units of fresh frozen plasma. Plasma ceftriaxone concentrations decreased from 89 +/- 34 to 41 +/- 16.5 micrograms/ml from the beginning of the operation until the time of closure of the peritoneum. Corresponding levels in epiploic fat decreased from 8.7 +/- 3.3 to 4.5 +/- 3.5 micrograms/g. Ornidazole concentrations ranged, respectively, between 8.7 +/- 2.5 and 4.9 +/- 1.7 micrograms/ml in plasma samples and 4.6 +/- 1.2 and 2.5 +/- 1.1. micrograms/g in fat samples. Rates of penetration into the omentum remained at about 9% for ceftriaxone and between 50 and 70% for ornidazole. Tissue ceftriaxone concentrations were, in all cases, greater than typical MICs for 90% for Escherichia coli and Klebsiella isolates tested (MIC90S). They were insufficient in 40% of patients after 60 min with regard to the MIC90S for Staphylococcus aureus. Tissue ornidazole concentrations were not superior to MIC90S for anaerobes after 30 min in 50% of patients. These results show that a single dose of 1 g of ceftriaxone provides adequate coverage against gram-negative bacteria and that 1 g instead of 500 mg ornidazole may provide a protective effect against anaerobes during liver transplantation. Prophylaxis against S. aureus and Streptococcus faecalis requires more specific antibiotics. Prophylaxis for patients with significant blood loss or initial severe renal or hepatic failure needs further evaluation.