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A pharmacologic evaluation of penicillin in children with purulent meningitis
Insights
Penicillin G levels in cerebrospinal fluid decrease during treatment for childhood meningitis. This dosage is generally effective, but higher doses may be needed for resistant bacteria.
Area of Science:
- Pharmacology
- Pediatrics
- Infectious Diseases
Background:
- Purulent meningitis in children poses significant treatment challenges.
- Understanding drug penetration into the cerebrospinal fluid (CSF) is crucial for effective therapy.
- Penicillin G is a primary antibiotic used for bacterial meningitis.
Purpose of the Study:
- To investigate the pharmacokinetics of intravenous penicillin G in the CSF of children with purulent meningitis.
- To assess how CSF penicillin concentrations change over the course of therapy.
- To correlate CSF penicillin levels with clinical and biochemical markers of meningitis resolution.
Main Methods:
- Prospective study design.
- Intravenous administration of penicillin G (50,000 U/kg/day) every four hours.
- Measurement of penicillin concentrations in CSF and serum on days 1, 5, and 10 of therapy.
- Monitoring of CSF protein concentration.
Main Results:
- Mean CSF penicillin concentrations decreased from 0.8 µg/mL on day 1 to 0.3 µg/mL on day 10.
- The percentage of serum penicillin concentration found in CSF also declined over time (18.4% to 4.9%).
- Peak CSF penicillin concentrations (mean 0.96 µg/mL) were transiently achieved.
- Decreasing CSF penicillin levels correlated with normalizing CSF protein concentrations (P < 0.01).
Conclusions:
- The studied dosage of penicillin G provides adequate CSF concentrations for most pediatric streptococcal and meningococcal meningitis cases.
- Therapeutic efficacy may be limited in cases with high minimal inhibitory concentrations (MICs) of penicillin for the causative pathogen.
- Consideration of increased penicillin G dosage may be warranted for meningitis caused by less susceptible bacterial strains.
Abstract:
We undertook a prospective study of the pharmacokinetics of penicillin G (administered intravenously every four hours for a total of b50,000 U per kilogram per day) in the cerebrospinal fluid of children with purulent meningitis. Both the absolute mean cerebrospinal-fluid penicillin concentration (0.8, 0.7 and 0.3 microgram per milliliter) and the percentage of the simultaneous serum penicillin concentration measurable in the cerebrospinal fluid (18.4, 9.9, 4.9 per cent) declined on the first, fifth and 10th days of therapy, respectively. A mean peak cerebrospinal-fluid penicillin concentration of 0.96 micrograms per milliliter was measured at least transiently on all three study days. This pharmacokinetic pattern correlated with the return of cerebrospinal-fluid protein concentration toward normal (P less than 0.01). Penicillin G in the dosage studied is adequate therapy for most streptococcal and meningococcal meningitis in children; an increased dosage may be necessary when the minimal inhibitory concentration of penicillin to the etiologic agent is unusually high.