desacetylcefotaxime and Postoperative-Complications

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.

Topics: Adult; Ampicillin; Cefotaxime; Chromatography, High Pressure Liquid; Female; Gram-Negative Bacteria; Humans; Liver Transplantation; Male; Middle Aged; Pilot Projects; Postoperative Complications; Premedication

A scarcity of pharmacokinetic data are available on cefotaxime in the obstetric patient. Fifteen patients received either 1 or 2 gm of cefotaxime after cesarean section. After intravenous administration of the designated dose, serial blood samples were analyzed for cefotaxime and its active metabolite, desacetyl cefotaxime (DCTX), by high-pressure liquid chromatography. The mean (+/- SD) peak concentrations of cefotaxime were 14.1 +/- 7.9 micrograms/ml and 40.0 +/- 32.5 micrograms/ml for the 1- and 2-gm dosage regimens, respectively. Detectable trough concentrations were 0.87 +/- 0.24 and 1.0 +/- 0.26, respectively, with many values falling below the sensitivity limits of the assay (0.5 micrograms/ml). The mean peak concentrations of DCTX for the two doses were 5.5 +/- 1.9 micrograms/ml and 10.9 +/- 6.2 micrograms/ml, respectively. Measurable trough levels for DCTX were more frequently identified, than for cefotaxime, at the end of the dosing interval due to an extended half-life as compared to its parent compound. Pharmacokinetic parameters of cefotaxime demonstrated large volumes of distribution and high clearance rates. Our data suggest altered pharmacokinetics of this agent in the obstetric patient when compared to previous studies in nonpregnant patients. This may be important in the seriously ill gravida where dosage adjustments in cefotaxime administration may be needed.

Topics: Adult; Cefotaxime; Chromatography, High Pressure Liquid; Female; Half-Life; Humans; Postoperative Complications; Postpartum Period; Pregnancy; Puerperal Infection