Penetration of fosfomycin into cerebrospinal fluid across non-inflamed and inflamed meninges.
Serum and cerebrospinal fluid (CSF) concentrations of fosfomycin were evaluated in 45 patients. Mean serum concentration was 260.1 mg/l at 15 min postinfusion in 35 patients receiving a 5 g bolus dose, and 440 mg/l in five patients receiving a 10 g bolus dose. Mean distribution volume was 18.5 l (5 g dose), the total clearance was 118.8 ml/min, half-life was nearly 2 h, and the determined AUC were 420.95 mg/l.h (5 g dose) and 423.57 mg/l.h (10 g dose). The average peaks at 360 min in CSF reached 11.6 mg/l (5 g dose) and 17.7 mg/l (10 g dose). The CSF/serum ratio was 9.24% (5 g dose), and 13.81% (10 g dose). The CSF levels were not below 30 mg/l from the second day on in patients receiving 3 X 5 g fosfomycin per day. Meningeal inflammation increased the CSF concentrations from 30 mg/l at 6 h up to 150 mg/l at 120 h in the saturation phase, e. g., up to 300% more in comparison to non-inflamed meninges.
Institut für Medizinische Mikrobiologie und Immunologie, Universitätsklinik Bonn.
E
E
Kühnen
G
G
Pfeifer
C
C
Frenkel
D000293:Adolescent; D000328:Adult; D000368:Aged; D005578:Fosfomycin / Q000097:blood / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics; D006801:Humans; D008578:Meninges / Q000378:metabolism*; D008581:Meningitis / Q000378:metabolism*; D008875:Middle Aged
D005578:Fosfomycin