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.

Primary pyogenic ventriculitis caused by Neisseria meningitidis: case report and review of the literature

“…Even if the meninges are inflamed, the penetration of intravenous vancomycin into cerebrospinal fluid is poor [11]. Few studies have been published assessing the pharmacokinetics and clinical utility of intraventricular administration of agents such as vancomycin and aminoglycosides [12]. …”

Strategies to reduce external ventricular drain–related infections: a multicenter retrospective study

“…29 According to a recent systematic review, the administration of aminoglycosides via this route appeared safe and effective for the treatment of EVD-related infections. 16 Although the prophylactic effectiveness of such action needs to be confirmed, all 3 cases of ventriculitis in the Grenoble cohort presented after EVD removal (see Appendix 2). Ventricular contamination may happen during the stripping of the drain.…”

Intrathecal tobramycin and pausing induction chemotherapy for pediatric acute lymphoblastic leukemia facilitate successful management of disseminated Pseudomonas aeruginosa infection and meningitis

“…12 Furthermore, intrathecal aminoglycosides reportedly are not associated with severe or irreversible toxicity. 13 Interruptions to chemotherapy during the induction phase of ALL treatment are avoided as they increase the risk of disease progression and, consequently, evidence on when an interruption in induction chemotherapy is justified remains nonexistent. 14 The present case highlights the importance of investigating the potential of day 15 MRD response to guide the continuation of induction chemotherapy in the case of concomitant severe infection, which is listed as a study question in the current European study protocol ALLTogether (ClinicalTrials.gov NCT03911128).…”