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 (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.

[1]  C. Quentin,et al.  In vitro activity of fosfomycin combined with ceftazidime, imipenem, amikacin, and ciprofloxacin againstPseudomonas aeruginosa , 1997, European Journal of Clinical Microbiology and Infectious Diseases.

[2]  T. Staudinger,et al.  Pharmacokinetics of teicoplanin during continuous hemofiltration with a new and a 24-h used highly permeable membrane: rationale for therapeutic drug monitoring-guided dosage. , 2004, International journal of clinical pharmacology and therapeutics.

[3]  W. Jaeger,et al.  How to Calculate Clearance of Highly Protein-Bound Drugs during Continuous Venovenous Hemofiltration Demonstrated with Flucloxacillin , 2003, Kidney and Blood Pressure Research.

[4]  M. Zeitlinger,et al.  Target site bacterial killing of cefpirome and fosfomycin in critically ill patients. , 2003, International journal of antimicrobial agents.

[5]  A. Geppert,et al.  Target site penetration of fosfomycin in critically ill patients. , 2003, The Journal of antimicrobial chemotherapy.

[6]  K. Ratheiser,et al.  Clearance of ceftazidime during continuous venovenous haemofiltration in critically ill patients. , 2002, The Journal of antimicrobial chemotherapy.

[7]  F. Allerberger,et al.  In vitro activity of fosfomycin in combination with various antistaphylococcal substances. , 2001, The Journal of antimicrobial chemotherapy.

[8]  U. Kroh Pharmacokinetic studies in patients on continuous renal replacement therapies , 2001, Intensive Care Medicine.

[9]  F. Crokaert Pharmacodynamics, a tool for a better use of antibiotics? , 2001, Intensive Care Medicine.

[10]  A. Georgopoulos,et al.  Distribution and Antimicrobial Activity of Fosfomycin in the Interstitial Fluid of Human Soft Tissues , 2000, Antimicrobial Agents and Chemotherapy.

[11]  J. Donauer,et al.  Pharmacokinetic principles during continuous renal replacement therapy: drugs and dosage. , 1999, Kidney international. Supplement.

[12]  K. Ratheiser,et al.  Single-Dose Pharmacokinetics of Meropenem during Continuous Venovenous Hemofiltration , 1998, Antimicrobial Agents and Chemotherapy.

[13]  M. A. Marx,et al.  Drug dosing adjustments during continuous renal replacement therapies. , 1998, Kidney international. Supplement.

[14]  G. Mayer,et al.  Multiple‐dose pharmacokinetics of cefpirome in long‐term hemodialysis with high‐flux membranes , 1996, Clinical pharmacology and therapeutics.

[15]  M. J. Renedo,et al.  Determination of fosfomycin in human urine by capillary gas chromatography: Application to clinical pharmacokinetic studies , 1996 .

[16]  S. Cotterill Antimicrobial prescribing in patients on haemofiltration. , 1995, The Journal of antimicrobial chemotherapy.

[17]  Jerome J. Schentag,et al.  The Importance of Pharmacokinetic/Pharmacodynamic Surrogate Markers to Outcome , 1995, Clinical pharmacokinetics.

[18]  B. Canaud,et al.  Pump assisted continuous venovenous hemofiltration for treating acute uremia. , 1988, Kidney international. Supplement.

[19]  G. Vinçon,et al.  Pharmacokinetics of fosfomycin in hemodialyzed patients. , 1985, Clinical Nephrology.

[20]  F. Dalet,et al.  Pharmacokinetics of fosfomycin during hemodialysis. , 1977, Chemotherapy.