Pharmacokinetics of cefpirome during the posttraumatic systemic inflammatory response syndrome.
OBJECTIVE
To determine the pharmacokinetic parameters of cefpirome, a new so-called fourth-generation cephalosporin, in previously healthy trauma patients with posttraumatic systemic inflammatory response syndrome (SIRS) and to compare them to parameters obtained in matched, healthy volunteers.


METHODS
A prospective study.


METHODS
12-bed surgical intensive care unit in a university hospital.


METHODS
9 severe [Injury Severity Score, median (range) 29 (16-50)] trauma patients on mechanical ventilation with proven or suspected cefpirome-susceptible nosocomial infection, with no renal or hepatic failure, and healthy volunteers matched for age (+/- 5 years), sex, and body surface area (+/- 10%) were enrolled. All were men.


METHODS
Cefpirome (2 g twice daily) was continuously infused over a 0.5 h period alone or concomitantly with ciprofloxacin (400 mg over 1 h, twice daily).


RESULTS
Antibiotic concentrations in plasma were measured by high-performance liquid chromatography; their pharmacokinetic parameters were evaluated at 12 time points after the first drug administration using a noncompartmental model. Cefpirome pharmacokinetic parameters for the two groups were similar despite a wider variation for trauma patients. Specifically, the median (range) time during which the cefpirome concentration in plasma remained over 4 mg/l (corresponding to the French lower cutoff determining cefpirome susceptibility) was 9.5 (7- > 12) and 9 (8-12) h for trauma patients and healthy volunteers, respectively. In the group of five patients receiving combined antibiotic therapy, the interindividual variability of pharmacokinetics was wider for ciprofloxacin than for cefpirome.


CONCLUSIONS
No major pharmacokinetic modification was noted when cefpirome was given to trauma patients with posttraumatic SIRS without significant organ failure, indicating that no dosage adjustment seems required in this population. However, larger studies including determination of antibiotic levels in tissues are warranted to confirm these results.
Service d'Anesthésie-Réanimation, Hôpital Bicêtre, Le Kremlin Bicêtre, France.
A
A
Jacolot
P
P
Incagnoli
A R
AR
Edouard
M
M
Tod
O
O
Petitjean
K
K
Samii
O
O
Mimoz
D000328:Adult; D000890:Anti-Infective Agents / Q000493:pharmacokinetics; D016022:Case-Control Studies; D002511:Cephalosporins / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002939:Ciprofloxacin / Q000493:pharmacokinetics; D004359:Drug Therapy, Combination; D006801:Humans; D007262:Infusions, Intravenous; D016018:Least-Squares Analysis; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011446:Prospective Studies; D018709:Statistics, Nonparametric; D018746:Systemic Inflammatory Response Syndrome / Q000188:drug therapy* / Q000209:etiology; D014947:Wounds and Injuries / Q000150:complications*; D000097572:Cefpirome
D000890:Anti-Infective Agents; D002511:Cephalosporins; D002939:Ciprofloxacin; D000097572:Cefpirome