Administration of Vancomycin at High Doses in Patients with Post Neurosurgical Meningitis: A Comprehensive Comparison between Continuous Infusion and Intermittent Infusion

Document Type: Research article

Authors

1 Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

2 Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti Medical University, Tehran, Iran.

3 Department of Infectious Diseases and Tropical Medicine, Loghman Hakim Hospital, Shahid Beheshti Medical University, Tehran, Iran.

4 Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

5 Department of Epidemiology, School of Public Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Abstract

Poor penetration of vancomycin into Central Nervous System (CNS) can lead to treatment
failure. The aim of this study was to evaluate and compare CSF concentration and serum
pharmacokinetics of high dose vancomycin by continuous infusion vs. intermittent infusion in
post neurosurgical meningitis patients. Twenty patients were divided into two groups. Patients
in intermittent infusion group received vancomycin as a loading dose of 25 mg/kg over two
hours, followed by 25 mg/kg over two hours every 12 h. In the Continuous Infusion group,
patients received vancomycin as a loading dose of 25 mg/kg over two hours, followed by 50
mg/kg/day by continuous infusion. In the intermittent infusion group, mean ± SD of serum
trough, peak and CSF concentrations were 17.49 ± 2.46 mg/L, 41.33 ± 2.73 mg/L, and 4.83
± 1.05 mg/L, respectively. Mean of CSF/trough% ratio was 27.39 ± 2.43%. A positive linear
correlation was found between the serum trough levels and CSF levels (r = 0.970, P < 0.001).
In continuous infusion group, mean ± SD of serum and CSF concentrations were 24.76 ± 2.02
mg/L and 6.20 ± 1.31 mg/L respectively. Mean ± SD of CSF/serum% ratio was 24.84% ±
3.54%. The serum and CSF levels revealed positive linear correlation (r = 0.902, P < 0.001).
The mean of CSF concentration in CI group was 6.20 ± 1.31 mg/L which was significantly
higher than II group (4.83 ± 1.05 mg/L, P < 0.019). CSF/serum ratio did not show any
significant difference between the two groups. Continuous infusion of vancomycin makes it
possible to achieve faster and constant target level in serum but did not have any significant
effect on the penetration (CSF/Serum ratio) of vancomycin in to the CNS.

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