Pharmacokinetics of cefpirome in critically ill patients with renal failure treated by continuous veno-venous hemofiltration

Objective: To study the cefpirome pharmacokinetics of patients with sepsis and multiple organ failure treated with CVVH. Design: Measurements of serum and ultrafiltrate (UF) concentrations and in vitro sensitivity testing of isolated micro-organisms. Setting: University hospital-based, single ICU. Patients: Six critically ill CVVH-dependent patients with sepsis and multiple organ dysfunction syndrome in need of antimicrobial therapy. Age range: 60-75 years; APACHE II score for severity of illness on admission: 19-30. One patient survived. Interventions: Cefpirome i. v. was started at 2 g in 30 min, then continued 1 g i. v. b. i. d. Measurements: The UF rate was 27 +/- 7 ml/min on day 1 and 34 +/- 2 ml/min on day 2. Serum and ultrafiltrate samples were measured by a validated high performance liquid chromatography assay. Volume of distribution: 23.5 (SD +/- 4.6) 1. Total cefpirome clearance was 32 +/- 6.3 ml/min; cefpirome CVVH clearance (Cl-CVVH): 17 +/- 4.2 ml/min; mean serum half-life (t(1/2)): 8.8 +/- 2.3 h; mass transfer on day 1: 660 +/- 123 mg/12 h (33 +/- 6 % of administered dose)and day 2: 642 +/- 66 mg/12 h (64 +/- 7%). Estimated sieving coefficient (Cl-CVVH/ UF rate): 64 +/- 11%. In vitro sensitivity of isolated microbes was excellent except for two non-sensitive enterococci and Candida spp. Conclusions: The sieving coefficient (64 %) indicates that a substantial fraction of the drug is not filtered; clearance by pathways other than CVVH mounted to 50 % of the total clearance and increased on day 2, indicating that the dosing schedule used is appropriate for this setting. Cefpirome appeared to be safe in these patients and effective for most of the nosocomial microbial isolates. During more than 90 % of the time, serum levels were maintained above killing concentrations for susceptible micro-organisms.