fosfomycin and Renal-Insufficiency

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).. 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.. 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.. 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.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Area Under Curve; Bacterial Infections; Blood Chemical Analysis; Chromatography, Gas; Drug Administration Schedule; Female; Fosfomycin; Hemofiltration; Humans; Male; Metabolic Clearance Rate; Middle Aged; Renal Insufficiency; Time Factors

Topics: Adult; Aged; Anti-Bacterial Agents; Defibrillators, Implantable; Drug Therapy, Combination; Endocarditis, Bacterial; Female; Fosfomycin; Heart Valve Prosthesis; Humans; Male; Middle Aged; Pacemaker, Artificial; Prosthesis-Related Infections; Renal Insufficiency; Vancomycin

The urinary concentrations of fosfomycin in 7 elderly patients with impaired renal function (mean creatinine clearance 40 ml/min) were studied after a single oral dose of 3 g fosfomycin as the trometamol salt. Urine samples were collected as 12 h portions for 84 h. Urinary concentrations of fosfomycin were 1,383 mg/l (range 314 to 4,200 mg/l) in the first 12 h and gradually declined to 165 mg/l (range 65 to 365 mg/l) between 36 and 48 h. 37% of the oral dose was recovered in the urine unchanged after 84 h, but a wide range (15-60%) in urinary recovery was observed. The elimination half-lives in the patients (estimated from the renal excretion profile of fosfomycin) ranged between 7 and 24 h. These data suggest that the urinary levels obtained in this patient population exceed the minimum inhibiting concentration of the usual pathogens involved in uncomplicated cystitis for at least 48 h. After 24 h the urinary concentrations of fosfomycin are higher than those reported for healthy young subjects.

Topics: Administration, Oral; Aged; Aged, 80 and over; Creatinine; Female; Fosfomycin; Half-Life; Humans; Nursing Homes; Renal Insufficiency