Pharmacology of cefotaxime and its desacetyl metabolite in renal and hepatic disease

Section: Discussionsupporting

confidence: 78%

Cefotaxime and desacetylcefotaxime pharmacokinetics in infants and children with meningitis

Trang¹,

Jacobs²,

Kearns³

et al. 1985

“…Substantial distribution of cefotaxime and ampicillin into extravascular fluids and tissues that act as reservoirs from which the antibiotics can reenter the circulation probably is an important factor contributing to the "normal" levels in serum in the liver transplant patients we studied (35). Also, the impaired hepatic and renal functions of our patients probably increased the elimination half-lives of cefotaxime and ampicillin intraoperatively (15,22,41), partially compensating for antibiotic loss caused by bleeding.…”

Section: Discussionmentioning

confidence: 99%

Microbiological efficacy and pharmacokinetics of prophylactic antibiotics in liver transplant patients

Arnow

Furmaga

Flaherty

et al. 1992

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 ,ig/ml) and trough (6.9 + 4.7 ,g/ml) levels of cefotaxime in serum and the first dose peak (73 ± 22 ,ug/ml) and trough (4.1 + 2.3 ,ug/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 pg/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.Bacterial and fungal infections frequently complicate orthotopic liver transplantation (OLT), despite routine perioperative prophylaxis with broad-spectrum antibiotics and sometimes antifungal agents. Most liver transplant patients experience at least one serious bacterial infection (11, 16), and the incidence of fungal infection has ranged from 16 to 42% (4,6,17,38). The characteristics of posttransplant bacterial and fungal infections are that most occur during the first few weeks after transplantation; the predominant pathogens in each category are aerobic gram-negative bacilli (AGNB) and Candida albicans; and the most common sites of infection are the abdomen, lower respiratory tract, and bloodstream (4,6,11,16,17,38). These features suggest that posttransplant infections usually result from perioperative inoculation or translocation of potentially pathogenic bowel flora into the abdomen and bloodstream or from aspiration of oropharyngeal AGNB.In an effort to reduce the incidence of posttransplant infection beyond that achieved with systemic antibiotic prophylaxis, several centers have supplemented systemic antibiotics with regimens of topical oropharyngeal and oral nonabsorbable antimicrobial agents to selectively eliminate AG...

“…Although the renal clearance of CTX in patients with end-stage renal disease is significantly decreased, the halflife is generally less than 3 h (6,10,13). Thus, frequent doses may be required to maintain effective plasma and peritoneal fluid concentrations.…”

Section: Pg/mi)mentioning

confidence: 99%

Disposition of cefotaxime and desacetyl cefotaxime during continuous ambulatory peritoneal dialysis

Heim¹,

Halstenson²,

Comty³

et al. 1986

The disposition of cefotaxime (CTX) and desacetyl cefotaxime (DAC) was studied in eight noninfected patients on continuous ambulatory peritoneal dialysis. Each patient received a single intravenous (i.v.) infusion and an intraperitoneal (i.p.) instillation of 2 g of CTX. Multiple blood and dialysate samples were collected during the 72-h period after drug administration. The half-life, steady-state volume of distribution, and total body clearance of CTX following i.v. administration were 2.2 ± 1.0 h (mean ± standard deviation), 0.17 ± 0.03 liters/kg, and 81.0 ± 31.0 ml/min, respectively. No significant differences were observed in these parameters after i.p. administration. The continuous ambulatory peritoneal dialysis clearances of CTX and DAC were 1.82 ± 0.43 and 2.84 ± 0.70 ml/min, respectively, after i.v. administration. The bioavailability of CTX after i.p. instillation was 74.6 ± 21.3%. Peak peritoneal dialysate CTX and DAC concentrations of 264.3 and 25.8 mg/liter, respectively, were observed after i