title: Serum and cerebrospinal fluid concentrations of linezolid in neurosurgical patients.
abstract: Linezolid is a new antimicrobial agent effective against drug-resistant gram-positive pathogens commonly responsible for central nervous system (CNS) infections in neurosurgical patients hospitalized in intensive care units. In order to study the penetration of this antimicrobial into the cerebrospinal fluid (CSF) of such patients, the disposition of linezolid in serum and CSF was studied in 14 neurosurgical patients given linezolid at 600 mg twice daily (1-h intravenous infusion) for the treatment of CNS infections caused by gram-positive pathogens or for prophylactic chemotherapy. Serum and CSF linezolid steady-state concentrations were analyzed by high-pressure liquid chromatography, and the concentration-time profiles obtained were analyzed to estimate pharmacokinetic parameters. The mean +/- standard deviation (SD) linezolid maximum and minimum measured concentrations were 18.6 +/- 9.6 microg/ml and 5.6 +/- 5.0 microg/ml, respectively, in serum and 10.8 +/- 5.7 microg/ml and 6.1 +/- 4.2 microg/ml, respectively, in CSF. The mean +/- SD areas under the concentration-time curves (AUCs) were 128.7 +/- 83.9 microg x h/ml for serum and 101.6 +/- 59.6 microg x h/ml for CSF, with a mean penetration ratio for the AUC for CSF to the AUC for serum of 0.66. The mean elimination half-life of linezolid in CSF was longer than that in serum (19.1 +/- 19.0 h and 6.5 +/- 3.6 h, respectively). The serum and CSF linezolid concentrations exceeded the pharmacodynamic breakpoint of 4 microg/ml for susceptible target pathogens for the entire dosing interval in the majority of patients. These findings suggest that linezolid may achieve adequate concentrations in the CSF of patients requiring antibiotics for the management or prophylaxis of CNS infections caused by gram-positive pathogens.
authors.affiliation: Athens University School of Nursing ICU, Athens, Greece.
authors.forename: Pavlos
authors.initials: P
authors.lastname: Myrianthefs
authors.forename: Sophia L
authors.initials: SL
authors.lastname: Markantonis
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Vlachos
authors.forename: Maria
authors.initials: M
authors.lastname: Anagnostaki
authors.forename: Eleni
authors.initials: E
authors.lastname: Boutzouka
authors.forename: Dimitris
authors.initials: D
authors.lastname: Panidis
authors.forename: Georgios
authors.initials: G
authors.lastname: Baltopoulos
mesh_terms: D000081:Acetamides / Q000097:blood* / Q000134:cerebrospinal fluid*; D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000097:blood* / Q000134:cerebrospinal fluid*; D019540:Area Under Curve; D001424:Bacterial Infections / Q000097:blood* / Q000134:cerebrospinal fluid / Q000188:drug therapy; D001927:Brain Diseases / Q000150:complications / Q000601:surgery*; D002851:Chromatography, High Pressure Liquid; D016638:Critical Illness; D005260:Female; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006207:Half-Life; D006801:Humans; D000069349:Linezolid; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D019635:Neurosurgical Procedures; D023303:Oxazolidinones / Q000097:blood* / Q000134:cerebrospinal fluid*; D011446:Prospective Studies
chemical_list: D000081:Acetamides; D000890:Anti-Infective Agents; D023303:Oxazolidinones; D000069349:Linezolid