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Aminoglycoside therapy of gram-negative bacillary meningitis
Abstract:
The distribution of aminoglycosides in the cerebrospinal fluid (CSF) space was examined after intralumbar, intraventricular, and systemic administration during seven episodes of gram-negative bacillary meningitis. Six episodes were associated with culture proved ventriculitis. Parenteral therapy with gentamicin or tobramycin produced low concentrations of aminoglycoside (less than 1.0 mug/ml) in the lumbar, ventricular, and cisternal CSF. Administration of 5 to 10 mg of aminoglycoside into the lumbar intrathecal space resulted in 27-81 mug/ml in the lumbar CSF, but 0-2.1 mug/ml in the ventricular CSF. In contrast, aminoglycoside administered into the cerebral ventricles produced concentrations in the lumbar CSF of 11.5-27.5 mug/ml and ventricular CSF of 12.8-40 mug/ml. All six episodes treated via the ventricular route resulted in a bacteriologic cure. Intraventricular administration of aminoglycosides offers a reliable means of achieving high aminoglycoside concentrations throughout the subarachnoid space.
Insights
Intraventricular aminoglycoside administration effectively treats gram-negative meningitis by achieving high drug concentrations in cerebrospinal fluid (CSF). This method is superior to intralumbar or systemic routes for reaching therapeutic levels throughout the subarachnoid space.
Area of Science:
- Pharmacology
- Infectious Diseases
- Neurosurgery
Background:
- Gram-negative bacillary meningitis is a serious infection requiring effective antibiotic delivery to the cerebrospinal fluid (CSF).
- Aminoglycosides are crucial antibiotics for treating gram-negative infections but achieving adequate CSF concentrations can be challenging.
- Previous studies indicated suboptimal aminoglycoside penetration into the CSF via systemic or intralumbar routes.
Purpose of the Study:
- To evaluate the distribution of aminoglycosides within the CSF space following different administration routes.
- To determine the efficacy of intraventricular aminoglycoside administration in treating gram-negative meningitis and ventriculitis.
- To compare CSF concentrations achieved by intralumbar, intraventricular, and systemic administration of aminoglycosides.
Main Methods:
- Seven episodes of gram-negative bacillary meningitis, six with ventriculitis, were studied.
- Aminoglycoside concentrations (gentamicin or tobramycin) were measured in lumbar, ventricular, and cisternal CSF.
- Administration routes included intralumbar, intraventricular, and systemic (parenteral) administration.
Main Results:
- Systemic and intralumbar administration resulted in low aminoglycoside concentrations (<1.0 mug/ml and 0-2.1 mug/ml in ventricular CSF, respectively).
- Intralumbar administration yielded high lumbar CSF levels (27-81 mug/ml) but poor ventricular penetration.
- Intraventricular administration achieved high concentrations in both ventricular (12.8-40 mug/ml) and lumbar CSF (11.5-27.5 mug/ml), leading to bacteriologic cure in all six ventriculitis cases.
Conclusions:
- Intraventricular aminoglycoside administration is a reliable method for achieving therapeutic drug concentrations throughout the subarachnoid space.
- This route is superior to intralumbar or systemic administration for treating gram-negative meningitis and ventriculitis.
- Optimizing antibiotic delivery to the CSF is critical for successful treatment outcomes in CNS infections.