Systematic Review of Efficacy, Pharmacokinetics, and Administration of Intraventricular Vancomycin in Adults

Abstract

Central nervous system infections requiring treatment with intraventricular (IVT) vancomycin are becoming increasingly common with advent of intracranial devices and increasing prevalence of multi-drug resistant and nosocomial organisms. Administering vancomycin via IVT route bypasses the blood-brain barrier to allow localized and controlled delivery directly to the desired site of action, achieving high concentrations for more reliable bactericidal action. This article systematically reviews current literature on IVT vancomycin in adults, compiles current knowledge, and integrates available evidence to serve as a practical reference.Medline (1946-July 2012), Embase (1974-July 2012), and International Pharmaceutical Abstracts (1970-July 2012) were searched using terms vancomycin, intraventricular, shunt infection, cerebrospinal fluid, and intraventriculitis. Seventeen articles were included in this review. Indications for IVT vancomycin included meningitis unresponsive to intravenous antibiotics, ventriculitis, and intracranial device infections. No serious adverse effects following IVT vancomycin have been reported. Dosages reported in literature ranged from 0.075-50 mg/day, with the most evidence for dosages of 5 to 20 mg/day. Duration of therapy most commonly ranged from 7 to 21 days. Therapeutic drug monitoring was reported in 11 studies, with CSF vancomycin levels varying widely from 1.1 to 812.6 mg/L, without clear relationships between CSF levels and efficacy or toxicity. Using IVT vancomycin to treat meningitis, ventriculitis, and CNS device-associated infections appears safe and effective based on current evidence. Optimal regimens are still unclear, and dosing of IVT vancomycin requires intricate consideration of patient specific factors and their impact on CNS pathophysiology. Higher-quality clinical trials are necessary to characterize the disposition of vancomycin within CNS, and to determine models for various pathophysiological conditions to facilitate better understanding of effects on pharmacokinetic and pharmacodynamic parameters.

2017 Infectious Diseases Society of America’s Clinical Practice Guidelines for Healthcare-Associated Ventriculitis and Meningitis*

“…Although there are methodological limitations in published studies, intraventricular vancomycin was shown to be safe and efficacious in a systematic review in adults [124]. Intraventricular aminoglycosides were also shown to be effective [122,126].…”

Surveillance and management of ventriculitis following neurosurgery

“…Consequently intraventricular vancomycin, either added if patients are unresponsive or at an initial diagnosis, is commonly used. 26 A dose of 5e20 mg/day administered by the intraventricular route results in mean trough CSF vancomycin levels of 81 mg/L with minimal, if any, adverse effects. 26 The intraventricular route is frequently used for treatment but not every centre monitors CSF levels.…”

“…26 A dose of 5e20 mg/day administered by the intraventricular route results in mean trough CSF vancomycin levels of 81 mg/L with minimal, if any, adverse effects. 26 The intraventricular route is frequently used for treatment but not every centre monitors CSF levels. However, there is insufficient evidence to support the use of prophylactic intraventricular vancomycin when inserting EVDs or VP shunts.…”

Drug Delivery Systems, CNS Protection, and the Blood Brain Barrier

“…Further, it is proved by fluorescence microscopy studies that FITC-D3 accumulates in the vacuolar compartments of the cells and can be detected in various structures and populations of cells after injection into the brain. Similarly, convection-enhanced delivery into the putamen nucleus [70], PDA, pressure support, surfactant therapy, inotropic drug administration, vaginal delivery, neonatal resuscitation, and antenatal corticosteroid therapy could be more significantly used higher in cases with IVH (intraventricular hemorrhage) [71]. It is mainly used to treat hyaline membrane disease and preeclampsia in mother [60].…”