Concentrations of fosfomycin in the cerebrospinal fluid of neurointensive care patients with ventriculostomy-associated ventriculitis

J Antimicrob Chemother. 2004 May;53(5):848-52. doi: 10.1093/jac/dkh158. Epub 2004 Mar 31.


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 < 0.03). 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.

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.

MeSH terms

  • Adult
  • Anti-Bacterial Agents / cerebrospinal fluid*
  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / pharmacology
  • Area Under Curve
  • Biological Assay
  • Cerebral Ventricles / pathology*
  • Critical Care*
  • Female
  • Fosfomycin / cerebrospinal fluid*
  • Fosfomycin / pharmacokinetics
  • Fosfomycin / pharmacology
  • Half-Life
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Neurosurgical Procedures / adverse effects*
  • Ventriculostomy / adverse effects*


  • Anti-Bacterial Agents
  • Fosfomycin