Concentrations of fosfomycin in the cerebrospinal fluid of neurointensive care patients with ventriculostomy-associated ventriculitis.
OBJECTIVE
The present study was performed to test the ability of fosfomycin to penetrate into the CSF of neurointensive care patients with ventriculostomy-associated ventriculitis.


METHODS
Six patients requiring neurointensive care monitoring, including extraventricular drainage due to secondary obstructive hydrocephalus, were enrolled into the study. All patients received 8 g of fosfomycin intravenously three times a day over a period of at least 5 days. Concentrations of fosfomycin in the CSF and plasma were measured after single-dose administration and at steady state.


RESULTS
Mean values of the fosfomycin area under the time-concentration curves for the dosing interval of 8 h (AUC(8)) were 929 +/- 280 and 225 +/- 131 mg.h/L for plasma and CSF after single-dose administration, respectively (P < 0.03). The ratios of the AUC(8) for CSF to the AUC(8) for plasma were 0.23 +/- 0.07 after a single dose and 0.27 +/- 0.08 following multiple doses (P > 0.05, not significant). Additional in vitro experiments have shown that fosfomycin exerts non-concentration-dependent microbial growth inhibition. At steady state, the time above MIC (t > MIC) values were 98%, 92% and 61% for pathogens with MIC values of 8, 16 and 32 mg/L, respectively.


CONCLUSIONS
The present pharmacokinetic study indicates that 8 g of fosfomycin three times per day should provide sufficient antimicrobial concentrations in the CSF for the overall treatment period. Thus, the co-administration of fosfomycin could be useful for the treatment of ventriculitis caused by susceptible pathogens.
Pfausler
Bettina
B
Department of Neurology, University Hospital, Innsbruck, Austria.
Spiss
Heinrich
H
Dittrich
Peter
P
Zeitlinger
Markus
M
Schmutzhard
Erich
E
Joukhadar
Christian
C
D000328:Adult; D000900:Anti-Bacterial Agents / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics / Q000494:pharmacology; D019540:Area Under Curve; D001681:Biological Assay; D002552:Cerebral Ventricles / Q000473:pathology*; D003422:Critical Care; D005260:Female; D005578:Fosfomycin / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics / Q000494:pharmacology; D006207:Half-Life; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D019635:Neurosurgical Procedures / Q000009:adverse effects*; D014696:Ventriculostomy / Q000009:adverse effects*
D000900:Anti-Bacterial Agents; D005578:Fosfomycin