Low cefpirome levels during twice daily dosing in critically ill septic patients: pharmacokinetic modelling calls for more frequent dosing

Objectives: To measure plasma levels and pharmacokinetics of cefpirome in critically ill septic patients with normal renal function. To use the pharmacokinetic model to simulate alternate dosing regimens and identify those that predict sustained levels. Design and setting: A prospective, open-label, descriptive study in a 22-bed, multidisciplinary, adult ICU in a university-affiliated, tertiary referral hospital. Patients: Twelve adults with normal renal function on enrolment and with suspected or documented sepsis in whom cefpirome was judged to be the appropriate therapy by the managing clinician. Interventions: Cefpirome 2 g was infused intravenously over 3 min every 12 h. Timed blood samples were taken prior to and during two dosing intervals. Urine was collected for creatinine clearance determination. Measurements and results: Two patients were non-evaluable due to renal dysfunction post-enrolment. The median cefpirome trough level was 1.1 mg/l (range 0.5–8.1 mg/l) after the initial dose and 1.4 mg/l (range