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Candidate, Facility for Anti-infective Drug Development and Innovation, Department of Pharmacy Practice, Victorian College of Pharmacy, Monash University, Parkville, Victoria, Australia
Senior Research Fellow, Facility for Anti-infective Drug Development and Innovation, Department of Pharmacy Practice, Victorian College of Pharmacy, Monash University
Associate Professor, Head of Microbiology and Deputy Director of Infectious Diseases, Alfred Hospital, Prahran, Victoria
Infectious Disease Physician, Department of Infectious Diseases, Alfred Hospital
Professor, Director, Facility for Anti-infective Drug Development and Innovation, and Head, Department of Pharmacy Practice, Victorian College of Pharmacy, Monash University
at time of writing, Co-Director, Facility for Anti-infective Drug Development and Innovation and Senior Lecturer of Department of Pharmacy Practice, Victorian College of Pharmacy, Monash University; now, Clinical Pharmacologist, Roche Products Ltd., Shire Park, Welwyn Garden City, England
Reprints: Dr. Nation, Facility for Anti-infective Drug Development and Innovation, Department of Pharmacy Practice, Victorian College of Pharmacy, Monash University, Parkville, Victoria 3052, Australia, fax 61 3 99039629, Roger.Nation{at}vcp.monash.edu.au
OBJECTIVE: To describe a case of coagulase-negative Staphylococcus ventriculitis successfully treated with oral linezolid, for which good cerebrospinal fluid (CSF) penetration was observed.
CASE SUMMARY: A 69-year-old man had an extraventricular drain inserted following a right cerebellar infarct. On day 6, the CSF culture was positive for coagulase-negative staphylococci; intravenous vancomycin 1 g daily was initiated to treat ventriculitis. A ventriculoperitoneal shunt, inserted on day 35 to manage communicating hydrocephalus, was subsequently removed as symptoms suggesting infection presented. Coagulase-negative Staphylococcus was isolated from shunt reservoir aspirate, and intrathecal vancomycin 10 mg daily was added to the treatment regimen. On day 61, vancomycin was stopped and oral linezolid 600 mg twice daily was started. Linezolid was discontinued 22 days later, with no evidence of ongoing infection. Four blood samples were collected around the seventh dose of linezolid and 5 CSF samples were collected on separate days during treatment. Linezolid concentrations were measured in plasma and CSF by HPLC. Using an ADAPT II maximum a priori Bayesian estimator module, a 2 compartment pharmacokinetic model was fitted to the plasma linezolid concentration data and CSF:predicted plasma concentration ratios (ranging from 0.27 to 1.02) were derived. All CSF concentrations exceeded the reported 90% minimum inhibitory concentration of 2 mg/L for linezolid against coagulase-negative staphylococci.
DISCUSSION: Evidence of the effectiveness of linezolid against central nervous system infections is growing; however, limited data exist describing its CSF penetration. Oral linezolid exhibited good CSF penetration in this patient, which corresponded to positive clinical response.
CONCLUSIONS: Oral linezolid may play a valuable role in the treatment of multiresistant gram-positive central nervous system infections.
Key Words: central nervous system infections, cerebrospinal fluid penetration, coagulase-negative Staphylococcus, linezolid
Published Online, June 13, 2006. www.theannals.com, DOI 10.1345/aph.1H029
This article has been cited by other articles:
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  F. Ntziora and M. E Falagas Linezolid for the Treatment of Patients with Central Nervous System Infection Ann. Pharmacother., February 1, 2007; 41(2): 296 - 308. [Abstract] [Full Text] [PDF]
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