title: Intraventricular daptomycin and intravenous linezolid for the treatment of external ventricular-drain-associated ventriculitis due to vancomycin-resistant Enterococcus faecium.
abstract: OBJECTIVE
  To report the successful treatment of external ventricular-drain (EVD)-associated infection due to vancomycin-resistant Enterococcus faecium (VRE) with intraventricular daptomycin and intravenous linezolid.
  
  
  METHODS
  A 64-year-old white male with a complicated medical history was admitted to the neurosurgical unit with Scedosporium apiospermum meningitis and hydrocephalus requiring management with a right and left EVD. On day 28, cerebrospinal fluid cultures from the right EVD grew VRE. Despite initiation of intravenous linezolid, cultures from the right EVD remained positive. Intraventricular daptomycin 5 mg daily was initiated and administered into the right EVD for 7 days. Cerebrospinal fluid was collected from EVD outputs and analyzed for daptomycin concentrations. VRE in cultures from the EVD cleared after 1 day of therapy and no adverse effects were noted. Right and left EVD daptomycin concentrations were discordant throughout therapy by at least a 3-fold difference. First-dose peak and trough daptomycin concentrations in the cerebrospinal fluid were 112.2 and 1.34 μg/mL, respectively, for the right EVD and 37.4 and 0.37 μg/mL, respectively, for the left EVD. Daptomycin accumulation was evident after 3 days of therapy.
  
  
  CONCLUSIONS
  Varying doses and frequencies of intraventricular daptomycin have been reported effective for VRE ventriculitis. Intraventricular drug distribution may not be homogeneous throughout the central nervous system. Therefore, daptomycin minimum inhibitory concentration for VRE, cerebrospinal fluid communication throughout the central nervous system, EVD output, and the potential for drug accumulation should be considered when selecting a dose and frequency.
  
  
  CONCLUSIONS
  Intraventricular daptomycin may be an option for EVD-associated VRE infections that do not respond to conventional therapy. Intraventricular daptomycin 5 mg is a reasonable initial dose in adults with VRE ventriculitis, based on our experience in this patient.
authors.affiliation: Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, USA. Scott.Mueller@ucdenver.edu
authors.forename: Scott W
authors.initials: SW
authors.lastname: Mueller
authors.forename: Tyree H
authors.initials: TH
authors.lastname: Kiser
authors.forename: Tracey A
authors.initials: TA
authors.lastname: Anderson
authors.forename: Robert T
authors.initials: RT
authors.lastname: Neumann
mesh_terms: D000081:Acetamides / Q000008:administration & dosage / Q000627:therapeutic use*; D061605:Administration, Intravenous; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000627:therapeutic use*; D058565:Cerebral Ventriculitis / Q000188:drug therapy / Q000382:microbiology; D017576:Daptomycin / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004322:Drainage; D004359:Drug Therapy, Combination; D016984:Enterococcus faecium / Q000187:drug effects; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D007276:Injections, Intraventricular; D000069349:Linezolid; D008297:Male; D008875:Middle Aged; D023303:Oxazolidinones / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D020713:Vancomycin Resistance
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D000069349:Linezolid; D017576:Daptomycin