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. PATIENTS AND 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 0.05, 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. CONCLUSION: 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.