Single-dose pharmacokinetics of fosfomycin during continuous venovenous haemofiltration

Objectives: Dosage recommendations for fosfomycin are available for haemodialysed patients but there are no data for patients undergoing continuous renal replacement therapy. Therefore, the present study was designed to determine the concentration-versus-time profile of fosfomycin in continuous venovenous haemofiltration (CVVH). Patients and methods: A total of 12 anuric intensive care patients(10 males and 2 females)with suspected or proven infection requiring parenteral antibiotic therapy were included in the study. All patients underwent CVVH. Blood samples were drawn from the arterial (input) and venous (output) line of the extracorporeal circuit after application of a single dose of 8 g of fosfomycin. Ultrafiltration samples were collected from the outlet of the ultrafiltrate compartment of the haemofilter. Fosfomycin in the samples was quantified by gas chromatography. Results: The peak serum concentration was 442.7 +/- 124 mg/L at the arterial port. The trough serum level was 103.1 +/- 36.6 mg/L at the arterial port after 720 min. The mean value of the area under the concentration-versus-time curve from 0 to 12 h (AUC(0-12)) was 2159.4 +/- 609.8 mg-h/L. Mean total removal of the drug was 76.7 +/- 6.2%. The mean calculated clearance was 1.1 +/- 0.2 L/h for CLHF. Mean CLtot was 6.4 +/- 7.7 L/h. Conclusions: A regimen of 8.0 g of fosfomycin every 12 h, which is usually used in patients with intact renal function, should be an appropriate antimicrobial treatment for patients undergoing CVVH.