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Abstract:
The penetration of mecillinam, a new beta-lactam penicillin-like antibiotic, into cerebrospinal fluid (CSF) was investigated in 11 children in whom all but 1 was presumed to have non-inflamed meninges. 30 minutes after a single intravenous dose of 30mg/kg, a concentration of approximately 0.30 micrograms/ml was achieved in the CSF (corresponding mean serum concentration 75 micrograms/ml), and this level was maintained during the next 4 hours in spite of rapidly declining serum concentrations, indicating a slow equilibration of mecillinam over the blood-liquor barrier. 1 child with suspected inflamed meninges showed a much higher CSF level of 12.1 micrograms/ml. It is concluded that mecillinam, as is the case for other penicillins, apparently crosses non-inflamed meninges poorly.
Insights
Mecillinam, a new antibiotic, poorly penetrates the cerebrospinal fluid (CSF) in children with non-inflamed meninges. Higher CSF concentrations were observed in a child with suspected inflamed meninges, suggesting altered barrier permeability.
Area of Science:
- Pharmacology
- Infectious Diseases
- Neurology
Background:
- Mecillinam is a novel beta-lactam antibiotic.
- Understanding antibiotic penetration into the central nervous system is crucial for treating meningitis.
Purpose of the Study:
- To investigate mecillinam's penetration into cerebrospinal fluid (CSF) in pediatric patients.
- To evaluate the influence of meningeal inflammation on mecillinam CSF concentrations.
Main Methods:
- Single intravenous dose of mecillinam (30mg/kg) administered to 11 children.
- CSF and serum concentrations of mecillinam were measured at various time points.
- Comparison of CSF levels in children with presumed non-inflamed meninges versus one child with suspected inflamed meninges.
Main Results:
- A mean CSF concentration of approximately 0.30 micrograms/ml was achieved 30 minutes post-dose in children with non-inflamed meninges.
- Mecillinam CSF levels remained relatively stable for 4 hours despite declining serum concentrations, indicating slow equilibration across the blood-liquor barrier.
- One child with suspected inflamed meninges exhibited a significantly higher CSF concentration (12.1 micrograms/ml).
Conclusions:
- Mecillinam demonstrates poor penetration into the CSF of children with non-inflamed meninges.
- Similar to other penicillins, mecillinam's passage across the blood-liquor barrier is limited under normal conditions.
- Inflammation of the meninges appears to enhance mecillinam's CSF penetration.