Linezolid brain penetration in neurointensive care patients.

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.

Risk factors for unfavorable outcome after spontaneous intracerebral hemorrhage in elderly patients.

BACKGROUND: Spontaneous intracerebral hemorrhage (SICH) of the elderly is a devastating form of stroke with a high morbidity and economic burden. There is still a limited understanding of the risk factors for an unfavorable outcome where a surgical therapy may be less meaningful. Thus, the aim of this study is to identify factors associated with unfavorable outcome and time to death in surgically treated elderly patients with SICH. METHODS: We performed a single-center retrospective study of 70 patients (age > 60 years) with SICH operated between 2008 and 2020. Functional outcome was assessed by modified Rankin Scale. Various clinical and neuroradiological variables including type of neurosurgical treatment, anatomical location of hemorrhage, volumetry and distribution of hemorrhage were assessed. Univariate and multivariate logistic regression models were performed. Length of stay (LOS) and hospital costs are presented. RESULTS: The overall mortality (mean follow-up time of 22 months) in this study was 32/70 patients (45.71%), 30-days mortality was 8/70 (11.42%), and 12-months mortality was 22/70 (31.43%). Average LOS was 73.5 days with a median of 58, 766 € estimated in hospital costs per patient. Multivariate analysis for 12-months mortality was significant for intraventricular hemorrhage (IVH) (p = 0.007, HR = 1.021, 95% CI = 1.006 - 1.037). ROC analysis for 12-months mortality for IVH volume >= 7 cm3 presented an are under the curve of 0.658. CONCLUSIONS: We identified IVH volume > 7 cm3 as an independent prognostic risk factor for mortality in elderly patients after SICH. This may help clinicians in decision-making for this critical and growing subgroup of patients.

Predicting the need for cerebrospinal fluid shunt implantation after spontaneous intracerebral hemorrhage: a challenging task.

Objectives: The development of persistent hydrocephalus in patients after spontaneous intracerebral hemorrhage (ICH) is still poorly understood, and many variables predicting the need for a cerebrospinal fluid (CSF)-shunt have been described in the literature with varying results. The aim of this study is to find predictive factors for shunt dependency. Methods: We performed a retrospective, single-center study of 99 neurosurgically treated patients with spontaneous ICH. Variables, including age, Glasgow Coma Scale (GCS), intraventricular hemorrhage (IVH), location of hemorrhage, acute hydrocephalus, and volumetric analysis of IVH, ICH, and intraventricular CSF were compared between patients with and without CSF-shunt implantation. Furthermore, receiver operating characteristics (ROC) for ICH, IVH, and intraventricular CSF volume parameters were calculated. Results: CSF-shunt implantation was performed significantly more often in patients after thalamic (p = 0.03) and cerebellar ICH (p = 0.04). Moreover, a lower ratio between the total hemorrhage volume and intraventricular CSF volume (p = 0.007), a higher IVH distribution in the third ventricle, and an acute hydrocephalus (p < 0.001) with an increased intraventricular CSF volume (p < 0.001) were associated with shunt dependency. Our ROC model demonstrated a sensitivity of 82% and a specificity of 65% to predict the necessity for a shunt at a cutoff value of 1.9 with an AUC of 0.835. Conclusion: Volumetric analysis of ICH, IVH, and intraventricular CSF may improve the prediction of CSF shunt implantation in patients with spontaneous ICH.