Pharmacokinetics of cefpirome during the posttraumatic systemic inflammatory response syndrome

Objective:To determine the pharmacokinetic parameters of cefpirome, a new s o-called fourth-generation cephalosporin, in previously healthy trauma pati ents with posttraumatic systemic inflammatory response syndrome (SIRS) and to compare them to parameters obtained in matched, healthy volunteers. Design: A prospective study. Setting: 12-bed surgical intensive care unit in a university hospital. Patients: 9 severe [Injury Severity Score, median (range) 29 (16-50)] traum a patients on mechanical ventilation with proven or suspected cefpirome-sus ceptible nosocomial infection, with no renal or hepatic failure, and health y volunteers matched for age ( +/- 5 years), sex, and body surface area (+/ - 10%) were enrolled. All were men. Interventions: Cefpirome (2 g twice daily) was continuously infused over a 0.5 h period alone or concomitantly with ciprofloxacin (400 mg over 1 h, tw ice daily). Measurements and main results: Antibiotic concentrations in plasma were mea sured by high-performance liquid chromatography; their pharmacokinetic para meters were evaluated at 12 time points after the first drug administration using a noncompartmental model. Cefpirome pharmacokinetic parameters for t he two groups were similar despite a wider variation for trauma patients, S pecifically, the median (range) time during which the cefpirome concentrati on 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 variab ility of pharmacokinetics was wider for ciprofloxacin than for cefpirome, Conclusion: No major pharmacokinetic modification was noted when cefpirome was given to trauma patients with posttraumatic SIRS without significant or gan failure, indicating that no dosage adjustment seems required in this po pulation. However, larger studies including determination of antibiotic lev els in tissues are warranted to confirm these results.