title: Systematic Review of Efficacy, Pharmacokinetics, and Administration of Intraventricular Aminoglycosides in Adults.
abstract: Due to increasing prevalence of intracranial device use and multidrug-resistant and nosocomial organisms, central nervous system (CNS) infections requiring treatment with intraventricular (IVT) aminoglycosides are becoming increasingly common. This article systematically reviews IVT aminoglycoside literature in adults and integrates available evidence to serve as a practical reference for clinicians. Medline (1946 to December 2015), Embase (1974 to December 2015), PubMed (1966 to December 2015), Google, and Google Scholar were searched using the term aminoglycoside combined individually with the terms IVT, meningitis, shunt infection, ventriculitis, and cerebral spinal fluid. Eighteen articles were included. IVT aminoglycosides were assessed in meningitis, ventriculitis, intracranial device infections and neurosurgery prophylaxis. No serious adverse effects following IVT aminoglycoside were reported. Dosages ranged from IVT gentamicin 4-10 mg daily, IVT tobramycin 5-10 mg daily, and IVT amikacin 5-50 mg daily. Duration of therapy should be individualized; however, continuing IVT antibiotics for 3 days and up to 21 days after cerebrospinal fluid (CSF) sterilization has been reported in literature. Most studies included concomitant intravenous antibiotic use. Therapeutic drug monitoring (TDM) was reported in five studies, with varying timing of CSF concentrations obtained. No clear relationship between CSF levels and efficacy or toxicity was evident. Based on current literature, IVT aminoglycosides for the treatment of sensitive gram-negative meningitis, ventriculitis, and CNS device-associated infections appear safe and effective. Optimal dosing regimens are unclear. It is reasonable to initiate IVT aminoglycoside at lowest dose in combination with IV therapy and continuing post CSF sterilization. Preservative-free formulations should be utilized to minimize adverse drug reactions. TDM should not be routinely utilized but reserved for more complicated patients. Further pharmacokinetic and clinical trials of IVT aminoglycosides are necessary to fill current therapeutic gaps. Due to the relatively limited cases of IVT aminoglycoside utilization, prospective, randomized, controlled trials are likely not feasible, and clinicians will have to rely on data from non-randomized and/or retrospective studies.
authors.affiliation: Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Marlys
authors.initials: M
authors.lastname: LeBras
authors.affiliation: Lower Mainland Pharmacy Services, Burnaby General Hospital, 3935 Kincaid Street, Burnaby, BC, V5G 2X6, Canada.
authors.forename: Ivy
authors.initials: I
authors.lastname: Chow
authors.affiliation: Lower Mainland Pharmacy Services, Burnaby General Hospital, 3935 Kincaid Street, Burnaby, BC, V5G 2X6, Canada. vincent.mabasa@fraserhealth.ca.
authors.forename: Vincent H
authors.initials: VH
authors.lastname: Mabasa
authors.affiliation: Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada.|Children's & Women's Health Centre of British Columbia, Vancouver, BC, Canada.
authors.forename: Mary H H
authors.initials: MH
authors.lastname: Ensom
mesh_terms: D000328:Adult; D000617:Aminoglycosides / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002494:Central Nervous System Infections / Q000188:drug therapy*; D003428:Cross Infection / Q000188:drug therapy*; D006801:Humans; D007276:Injections, Intraventricular
chemical_list: D000617:Aminoglycosides
keywords: Aminoglycoside; Intraventricular; Meningitis; Therapeutic drug monitoring; Ventriculitis