desacetylcefotaxime and Peritonitis

We have prospectively studied 13 episodes of spontaneous bacterial peritonitis (SBP) in 12 patients treated with cefotaxime (CTX) 2 g intravenously every 8 h (mean duration, 5.3 days). Ascitic fluid was inoculated at the bedside. The cultures were done before, during (day 3 after CTX initiation), and 48-72 h (mean, 56 h) after the end of therapy. All SBP episodes were monomicrobial. During treatment, the concentrations of CTX and desacetyl-cefotaxime (d-CTX) in ascitic fluid were high in all 13 SBP episodes, and d-CTX was still present in 6 patients who had residual ascitic bactericidal titer (ABT) activity after the last dose of CTX. ABTs were >/=1:128 during CTX therapy in 12 episodes and were measurable in 7 patients after the last dose. All patients were cured. The present study provides scientific rationale to the clinical studies that suggest treating SBP episodes with lower doses of antibiotics and shorter treatment duration.

Topics: Adult; Aged; Aged, 80 and over; Ascitic Fluid; Bacteria; Bacterial Infections; Cefotaxime; Cephalosporins; Female; Humans; Male; Middle Aged; Peritonitis; Prospective Studies

The aim of this study was to determine the steady-state plasma and peritoneal concentrations of cefotaxime and its metabolite desacetyl-cefotaxime administered by continuous infusion to critically ill patients with secondary peritonitis.. In 11 patients, a continuous infusion of 4 g/24 h of cefotaxime following a bolus of 2 g was evaluated. Plasma and peritoneal levels of cefotaxime and desacetyl-cefotaxime were measured at steady state on days 2 and 3 (plasma) and on day 3 (peritoneal) by HPLC. Results are expressed as means +/- SD.. Total and unbound plasma levels of cefotaxime were 24.0 +/- 21.5 and 20.3 +/- 19.8 mg/L on day 2 and 22.1 +/- 20.7 and 18.9 +/- 19.2 mg/L on day 3, respectively. Total and unbound levels of cefotaxime in the peritoneal fluids were 16.2 +/- 11.5 and 14.3 +/- 10.4 mg/L, respectively. The unbound fraction of plasma cefotaxime was 81.8 +/- 5.9% on day 2 and 82.6 +/- 7.7% on day 3, and the unbound fraction at the peritoneal site was 87.0 +/- 5.5% on day 3. Total and unbound plasma levels of desacetyl-cefotaxime were 9.0 +/- 8.1 and 8.4 +/- 8.1 mg/L on day 2 and 7.6 +/- 7.6 and 7.2 +/- 7.6 mg/L on day 3, respectively. Total and unbound levels of desacetyl-cefotaxime in the peritoneal fluids were 11.9 +/- 11.5 and 10.9 +/- 10.8 mg/L, respectively. The MICs for the enterobacteria recovered ranged from 0.016 to 0.25 mg/L.. Continuous infusion of 4 g/24 h of cefotaxime provided a peritoneal concentration >5x MIC for the recovered Enterobacteriaceae and the susceptibility breakpoint of cefotaxime for facultative Gram-negative bacilli.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Ascitic Fluid; Cefotaxime; Critical Illness; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Infusions, Intravenous; Male; Microbial Sensitivity Tests; Middle Aged; Peritonitis; Plasma

The pharmacokinetics of intraperitoneal cefotaxime as the sole therapy in patients on continuous ambulatory peritoneal dialysis with peritonitis have been examined. The mean plasma concentrations achieved following 1 h of peritoneal instillation of 500 mg of cefotaxime were 5.0 +/- 1.6 micrograms ml-1. The average plasma concentration over 24 h was 6.9 +/- 0.4 micrograms ml-1 and was no different from that found following a further 9-11 days of successful treatment of the peritonitis. However, the mean dialysate effluent concentration of cefotaxime was increased following the resolution of the peritonitis, 165 +/- 22.7 mg per cycle on day 10 or 12 compared with 50.4 +/- 7.3 mg per cycle on day 1, suggesting enhanced peritoneal cefotaxime absorption during acute peritonitis. Nevertheless, during both periods, adequate concentrations of cefotaxime were achieved in dialysate to treat local complications, but plasma levels may be inadequate to treat systemic complications due to Staphylococcus albus.

Topics: Adult; Aged; Cefotaxime; Humans; Kinetics; Male; Middle Aged; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis

The pharmacokinetics of cefotaxime were studied in 13 patients on haemodialysis or continuous ambulatory peritoneal dialysis (CAPD). One gram of cefotaxime was administered intravenously or intraperitoneally. In the haemodialysis patients, the serum concentration after 4h was 9.4 mg/l and the T1/2 was 1.31 h. The 6-h value and T1/2 in the CAPD (intravenous) patients were 4.5 mg/l and 1.59 hours, while the peak value in the dialysate was 11.6 mg/l. In the CAPD (intraperitoneal) patients, the cefotaxime concentration in the dialysate was 157 mg/l after 6 h and the peak value in the serum was 9.1 mg/l. Since cefotaxime is easily removed from the blood by both the haemodialysis and CAPD methods, accumulation of the drug in patients undergoing dialysis is unlikely to occur.

Topics: Adult; Aged; Cefotaxime; Female; Humans; Kinetics; Male; Middle Aged; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Renal Dialysis