Abstract
The pharmacokinetics of perioperative systemic antibiotics and the microbiological effectiveness of oral nonabsorbable antibiotics started immediately prior to surgery were studied in 18 adult patients undergoing liver transplantation. All patients received cefotaxime, 2 g intravenously, at 6-h intervals during surgery and then at 8-h intervals thereafter for 48 h; eight patients also received ampicillin at the same dose and schedule. This regimen produced levels of antibiotics in blood that appeared appropriate for prophylaxis. The first dose peak (68 +/- 18 micrograms/ml) and trough (6.9 +/- 4.7 micrograms/ml) levels of cefotaxime in serum and the first dose peak (73 +/- 22 micrograms/ml) and trough (4.1 +/- 2.3 micrograms/ml) levels of ampicillin in serum, which were assayed by high-performance liquid chromatography, were similar to levels reported in normal volunteers, despite mean intraoperative blood loss of 3.3 liters and fluid replacement of 21 liters. On postoperative days 1 and 2, the levels of cefotaxime and ampicillin were maintained at or above 0.9 and 1.3 micrograms/ml, respectively, with little accumulation. By random assignment, 8 patients received systemic antibiotics alone and 10 patients received systemic antibiotics plus a 3-week regimen of oral nonabsorbable antibiotics (gentamicin, polymyxin E, and nystatin) beginning when a donor liver was procured. Pre- and postoperative cultures of rectum, throat, and gastric aspirate samples showed persistence of aerobic gram-negative bacilli for the first 2 postoperative weeks in about half of the patients in each group. Failure of the regimen of oral nonabsorbable antibiotics to supplement cefotaxime in eradicating aerobic gram-negative bacilli from stools probably results from impaired peristalsis during and after surgery and warrants earlier initiation of the regimen.
Highlights
The pharmacokinetics of perioperative systemic antibiotics and the microbiological effectiveness of oral nonabsorbable antibiotics started immediately prior to surgery were studied in 18 adult patients undergoing liver transplantation
The timing of administration of oral nonabsorbable antibiotics, which often take at least 1 week to achieve selective bowel decontamination (SBD) [19], is problematic because of uncertainty about when a donor liver will be available. Interest in these issues, which may affect the efficacy of antibiotic prophylaxis, prompted us to conduct a pilot study in which we assessed the pharmacokinetics of systemic agents and the microbiological effectiveness of an SBD regimen started immediately prior to surgery
Adequate specimens for antibiotic level determinations were obtained from 15 patients, and appropriate specimens for culture were obtained from 17 patients
Summary
The pharmacokinetics of perioperative systemic antibiotics and the microbiological effectiveness of oral nonabsorbable antibiotics started immediately prior to surgery were studied in 18 adult patients undergoing liver transplantation. 5-ml samples of blood were obtained for determination of cefotaxime, desacetylcefotaxime, and ampicillin concentrations in serum prior to each dose and at 5, 15, 30, 60, 120, 180, 240, 300, and 360 min following antibiotic infusion.
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