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Antimicrobial Agents and Chemotherapy, December 2006, p. 3971-3976, Vol. 50, No. 12
0066-4804/06/$08.00+0     doi:10.1128/AAC.00051-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Serum and Cerebrospinal Fluid Concentrations of Linezolid in Neurosurgical Patients{triangledown}

Pavlos Myrianthefs,1 Sophia L. Markantonis,2* Konstantinos Vlachos,3 Maria Anagnostaki,2 Eleni Boutzouka,1 Dimitris Panidis,2 and Georgios Baltopoulos1

Athens University School of Nursing ICU, Athens, Greece,1 Athens University School of Pharmacy, Laboratory of Biopharmaceutics and Pharmacokinetics, Athens, Greece,2 Department of Neurosurgery, KAT General Hospital, Athens, Greece3

Received 12 January 2006/ Returned for modification 10 March 2006/ Accepted 8 September 2006

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 µg/ml and 5.6 ± 5.0 µg/ml, respectively, in serum and 10.8 ± 5.7 µg/ml and 6.1 ± 4.2 µg/ml, respectively, in CSF. The mean ± SD areas under the concentration-time curves (AUCs) were 128.7 ± 83.9 µg · h/ml for serum and 101.6 ± 59.6 µg · 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 µg/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.

* Corresponding author. Mailing address: Laboratory of Biopharmaceutics and Pharmacokinetics, School of Pharmacy, Panepistimiopolis, Athens 157.71, Greece. Phone: 30-210-7274676. Fax: 30-210-7274027. E-mail: kyroudi{at}pharm.uoa.gr.

{triangledown} Published ahead of print on 18 September 2006.

Antimicrobial Agents and Chemotherapy, December 2006, p. 3971-3976, Vol. 50, No. 12
0066-4804/06/$08.00+0     doi:10.1128/AAC.00051-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Nagel, S., Kohrmann, M., Huttner, H. B., Storch-Hagenlocher, B., Schwab, S. (2007). Linezolid-Induced Posterior Reversible Leukoencephalopathy Syndrome. Arch Neurol 64: 746-748 [Abstract] [Full Text]  
  • Beer, R., Engelhardt, K. W., Pfausler, B., Broessner, G., Helbok, R., Lackner, P., Brenneis, C., Kaehler, S. T., Georgopoulos, A., Schmutzhard, E. (2007). Pharmacokinetics of Intravenous Linezolid in Cerebrospinal Fluid and Plasma in Neurointensive Care Patients with Staphylococcal Ventriculitis Associated with External Ventricular Drains. Antimicrob. Agents Chemother. 51: 379-382 [Abstract] [Full Text]  


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