The Pharmacokinetics and Efficacy of an Aminoglycoside Administered into the Cerebral Ventricles in Neonates: Implications for Further Evaluation of This Route of Therapy in Meningitis

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Abstract
The optimal dose, frequency, and duration of intraventricular therapy for gram-negative meningitis (GNM) have never been determined. A prospective evaluation of the pharmacokinetics of intraventricular amikacin was undertaken in neonates with GNM. After the initial intraventricular instillation of 5 mg of amikacin via a Rickham reservoir, a lO-fold variation in the cerebrospinal fluid (CSF) concentration and a fivefold variation in half-life of the drug were noted. These variations were related to differences in the CSF volume secondary to hydrocephalus, myelomeningocele, and/or brain abscess. Successful therapy required maintaining the concentration of amikacin in CSF well above the minimal inhibitory concentration for the infecting organism at all times. A retrospective review of GNM demonstrated that the mortality was lower after intraventricular than after systemic therapy. These data suggest that if careful attention is given to the pharmacokinetics of intraventricular therapy, this route may be a valuable adjunct to therapy for GNM in neonates.

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