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JAC Advance Access originally published online on June 16, 2006
Journal of Antimicrobial Chemotherapy 2006 58(2):367-371; doi:10.1093/jac/dkl251
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Single-dose pharmacokinetics of fosfomycin during continuous venovenous haemofiltration

Rainer Gattringer1,*, Brigitte Meyer2, Gottfried Heinz2, Claudia Guttmann1, Markus Zeitlinger3, Christian Joukhadar3, Peter Dittrich4 and Florian Thalhammer1

1 Department of Internal Medicine I, Division of Infectious Diseases and Chemotherapy, Medical University of Vienna Vienna, Austria 2 Department of Internal Medicine II, Division of Intensive Care Medicine, Medical University of Vienna Vienna, Austria 3 Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, Medical University of Vienna Vienna, Austria 4 Department of Pharmacology, Karl-Franzens University Graz, Austria

Received 11 December 2005; returned 3 February 2006; revised 20 March 2006; accepted 24 May 2006

*Corresponding author. Tel: +43-1-40400-4440; Fax: +43-1-40400-4418; E-mail: rainer.gattringer{at}meduniwien.ac.at

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 (AUC0–12) 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.

Keywords: bactericidal agents , antibiotic agents , renal replacement therapy


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