Dataset Information

Linezolid brain penetration in neurointensive care patients.

ABSTRACT:

Background

Linezolid exposure in critically ill patients is associated with high inter-individual variability, potentially resulting in subtherapeutic antibiotic exposure. Linezolid exhibits good penetration into the CSF, but its penetration into cerebral interstitial fluid (ISF) is unknown.

Objectives

To determine linezolid penetration into CSF and cerebral ISF of neurointensive care patients.

Patients and methods

Five neurocritical care patients received 600 mg of linezolid IV twice daily for treatment of extracerebral infections. At steady state, blood and CSF samples were collected from arterial and ventricular catheters, and microdialysate was obtained from a cerebral intraparenchymal probe.

Results

The median fAUC0-24 was 57.6 (24.9-365) mg·h/L in plasma, 64.1 (43.5-306.1) mg·h/L in CSF, and 27.0 (10.7-217.6) mg·h/L in cerebral ISF. The median penetration ratio (fAUCbrain_or_CSF/fAUCplasma) was 0.5 (0.25-0.81) for cerebral ISF and 0.92 (0.79-1) for CSF. Cerebral ISF concentrations correlated well with plasma (R = 0.93, P < 0.001) and CSF levels (R = 0.93, P < 0.001).The median fAUC0-24/MIC ratio was ≥100 in plasma and CSF for MICs of ≤0.5 mg/L, and in cerebral ISF for MICs of ≤0.25 mg/L. The median fT>MIC was ≥80% of the dosing interval in CSF for MICs of ≤0.5 mg/L, and in plasma and cerebral ISF for MICs of ≤0.25 mg/L.

Conclusions

Linezolid demonstrates a high degree of cerebral penetration, and brain concentrations correlate well with plasma and CSF levels. However, substantial variability in plasma levels, and thus cerebral concentrations, may result in subtherapeutic tissue concentrations in critically ill patients with standard dosing, necessitating therapeutic drug monitoring.

SUBMITTER: Hosmann A

PROVIDER: S-EPMC10904716 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Publications

Linezolid brain penetration in neurointensive care patients.

Hosmann Arthur A Moser Miriam M MM van Os Wisse W Gramms Leon L Al Jalali Valentin V Sanz Codina Maria M Plöchl Walter W Lier Constantin C Kees Frieder F Dorn Christoph C Rössler Karl K Reinprecht Andrea A Zeitlinger Markus M

The Journal of antimicrobial chemotherapy 20240301 3

<h4>Background</h4>Linezolid exposure in critically ill patients is associated with high inter-individual variability, potentially resulting in subtherapeutic antibiotic exposure. Linezolid exhibits good penetration into the CSF, but its penetration into cerebral interstitial fluid (ISF) is unknown.<h4>Objectives</h4>To determine linezolid penetration into CSF and cerebral ISF of neurointensive care patients.<h4>Patients and methods</h4>Five neurocritical care patients received 600 mg of linezol ...[more]

PMID: 38323369

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Dataset Information

Linezolid brain penetration in neurointensive care patients.

Background

Objectives

Patients and methods

Results

Conclusions

Publications

Linezolid brain penetration in neurointensive care patients.

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