Penetration of parenterally administered gentamicin into the cerebrospinal fluid in experimental meningitis

Area of Science:

• Pharmacokinetics and Drug Delivery
• Infectious Diseases and Microbiology
• Veterinary Neurology

Background:

• Gentamicin is a critical antibiotic for treating Gram-negative bacterial infections.
• Understanding antibiotic penetration into the cerebrospinal fluid (CSF) is vital for treating central nervous system infections.
• Limited data exists on gentamicin's CSF penetration in inflammatory conditions like meningitis.

Purpose of the Study:

• To investigate the penetration of parenterally administered gentamicin into the canine cerebrospinal fluid (CSF).
• To compare gentamicin CSF penetration in healthy dogs versus dogs with experimentally induced meningitis.
• To determine if inflammation significantly alters gentamicin's ability to cross the blood-brain barrier.

Main Methods:

• Experiments were conducted in three groups of dogs: healthy, with meningitis, and recovering from meningitis.
• Gentamicin was administered parenterally, and its concentration in serum and CSF was measured.
• Pharmacokinetic parameters, including peak levels and CSF-to-serum ratios, were calculated.

Main Results:

• Gentamicin demonstrated poor penetration into the CSF in healthy dogs, with a mean peak CSF level of 0.7 µg/ml.
• In dogs with meningitis, mean peak CSF gentamicin levels increased to 0.9 µg/ml.
• The ratio of mean maximum CSF to mean maximum serum gentamicin levels was 5.8% in healthy dogs and 11.3% in dogs with meningitis, indicating increased penetration during inflammation.

Conclusions:

• Parenteral gentamicin penetration into the canine CSF is limited, even during meningeal inflammation.
• While meningitis increases gentamicin's CSF penetration, the achieved levels are insufficient for treating Gram-negative bacterial meningitis.
• Alternative or adjunctive therapeutic strategies may be necessary for effective treatment of canine meningitis with gentamicin.