title: Concentrations of fosfomycin in the cerebrospinal fluid of neurointensive care patients with ventriculostomy-associated ventriculitis.
abstract: 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.
authors.affiliation: Department of Neurology, University Hospital, Innsbruck, Austria.
authors.forename: Bettina
authors.initials: B
authors.lastname: Pfausler
authors.forename: Heinrich
authors.initials: H
authors.lastname: Spiss
authors.forename: Peter
authors.initials: P
authors.lastname: Dittrich
authors.forename: Markus
authors.initials: M
authors.lastname: Zeitlinger
authors.forename: Erich
authors.initials: E
authors.lastname: Schmutzhard
authors.forename: Christian
authors.initials: C
authors.lastname: Joukhadar
mesh_terms: 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*
chemical_list: D000900:Anti-Bacterial Agents; D005578:Fosfomycin