Ventricular cerebrospinal fluid concentrations of trimethoprim-sulphamethoxazole

Area of Science:

• Pharmacokinetics
• Infectious Diseases
• Neurosurgery

Background:

• Trimethoprim-sulphamethoxazole (TMP-SMZ) is a widely used antibiotic.
• Understanding its penetration into cerebrospinal fluid (CSF) is crucial for treating CNS infections.
• Meningeal inflammation often enhances antibiotic CSF penetration.

Purpose of the Study:

• To determine ventricular CSF concentrations of TMP-SMZ after intravenous administration.
• To assess if CSF TMP-SMZ levels exceed minimum inhibitory concentrations (MICs) for key pathogens.
• To evaluate the relationship between CSF drug levels and time post-administration.

Main Methods:

• Fifteen patients received a 1-hour IV infusion of TMP (5 mg/kg) and SMZ (25 mg/kg).
• Ventricular CSF samples were collected at varying times before surgery (within 8 hours).
• CSF drug concentrations were quantified and compared to established MICs.

Main Results:

• Mean ventricular CSF TMP concentration was 1.1 mg/L (range: 0.5-3.2 mg/L).
• Mean ventricular CSF SMZ concentration was 17.9 mg/L (range: 5-40 mg/L).
• In 11/14 patients, CSF levels exceeded MICs for Staphylococcus aureus and S. epidermidis, even without meningeal inflammation.

Conclusions:

• Intravenous TMP-SMZ achieves therapeutic concentrations in ventricular CSF.
• Significant CSF drug levels are attainable without the presence of meningeal inflammation.
• TMP-SMZ demonstrates potential efficacy against susceptible Staphylococcal infections in the CNS.