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Diffusion of moxalactam into the cerebrospinal fluid in children with bacterial meningitis
Abstract:
We studied the penetration of moxalactam into the cerebrospinal fluid of 16 children (age range one month to 4 1/2 years) who were being treated for bacterial meningitis. Two hours after single intravenous doses of 15 or 25 mg/kg, moxalactam was detectable in the CSF in only one of 11 instances; however, following three doses (50 mg/kg each) moxalactam was detectable in eight of 17 instances. In these eight instances CSF concentrations of moxalactam ranged between 1.5 and 18.9 micrograms/ml (mean 7.7) and the CSF/plasma ratio ranged from 2.6 to 36% (mean 17.7). There was no relation between the stage of meningitis or the CSF cell count and the diffusion of the drug into the CSF. However, the diffusion of the drug significantly correlated with the CSF protein content. In view of the unpredictability of moxalactam penetration into CSF, caution should be exercised in using it alone in the treatment of meningitis.
Insights
Moxalactam penetration into cerebrospinal fluid (CSF) is unpredictable in children with bacterial meningitis. Higher doses and CSF protein levels may influence drug diffusion, suggesting caution when using moxalactam alone.
Area of Science:
- Pharmacology
- Pediatrics
- Infectious Diseases
Background:
- Bacterial meningitis is a serious infection in children.
- Effective antibiotic penetration into the cerebrospinal fluid (CSF) is crucial for treatment.
- Moxalactam is a cephalosporin antibiotic used to treat bacterial infections.
Purpose of the Study:
- To investigate the penetration of moxalactam into the CSF of pediatric patients with bacterial meningitis.
- To determine factors influencing moxalactam's diffusion into the CSF.
Main Methods:
- Studied 16 children (1 month to 4.5 years) treated for bacterial meningitis.
- Administered single and multiple intravenous doses of moxalactam (15-50 mg/kg).
- Measured moxalactam concentrations in CSF and plasma, analyzing correlation with meningitis stage, CSF cell count, and CSF protein content.
Main Results:
- Moxalactam was detected in CSF in only 1 of 11 instances after single doses.
- Following multiple doses, moxalactam was detected in 8 of 17 instances.
- CSF concentrations ranged from 1.5 to 18.9 µg/ml (mean 7.7), with CSF/plasma ratios from 2.6% to 36% (mean 17.7%).
- Moxalactam diffusion correlated significantly with CSF protein content but not meningitis stage or cell count.
Conclusions:
- Moxalactam penetration into pediatric CSF is variable and unpredictable.
- CSF protein levels appear to influence moxalactam diffusion.
- Caution is advised when using moxalactam as monotherapy for bacterial meningitis due to inconsistent CSF penetration.