Plasma and peritoneal concentration following continuous infusion of cefotaxime in patients with secondary peritonitis

Abstract

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.