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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Seguin
Philippe
P
Service de Réanimation Chirurgicale-Inserm U620, Université Rennes 1, Hôpital de Pontchaillou, Rennes Cedex 9, Rennes, France. philippe.seguin@chu-rennes.fr
Verdier
Marie Clémence
MC
Chanavaz
Charles
C
Engrand
Charlotte
C
Laviolle
Bruno
B
Donnio
Pierre-Yves
PY
Mallédant
Yannick
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001202:Ascitic Fluid / Q000737:chemistry*; D002439:Cefotaxime / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D016638:Critical Illness; D004755:Enterobacteriaceae / Q000187:drug effects / Q000302:isolation & purification; D004756:Enterobacteriaceae Infections / Q000382:microbiology; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010538:Peritonitis / Q000188:drug therapy*; D010949:Plasma / Q000737:chemistry*
D000900:Anti-Bacterial Agents; C029281:desacetylcefotaxime; D002439:Cefotaxime