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Published on: November 5, 2019
Pharmacokinetics of cefamandole and ampicillin in experimental meningitis
Abstract:
The penetration of cefamandole and ampicillin into the cerebrospinal fluid of rabbits with and without pneumococcal meningitis was evaluated. In normal animals, a mean maximum concentration of 0.22 +/- 0.13 microgram of cefamandole per ml was measured in the spinal fluid after a dose of 150 mg/kg given intramuscularly; with 25 and 50 mg/kg doses, no antibiotic was detected in the cerebrospinal fluid. With ampicillin, in intramuscular doses of 200 and 300 mg/kg, the mean maximum concentrations encountered in the cerebrospinal fluid were 1.59 +/- 0.4 and 1.47 +/- 0.44 microgram/ml, respectively. Penetration of cefamandole, and to a lesser extent ampicillin, was increased after 24 h of experimental meningitis. With cefamandole, the concentration of drug in the cerebrospinal fluid exceeded the usual inhibitory concentration for Haemophilus influenzae only with the 150 mg/kg dose. After 48 h of meningitis, there was a trend toward higher levels of antibiotic in the cerebrospinal fluid, but the difference between animals infected 24 versus 48 h was not statistically significant. In animals with meningitis, serum concentrations after 150 mg of cefamandole per kg and both ampicillin doses studied were 32 to 38% lower than the serum levels achieved in normal rabbits after identical doses of antibiotic.
Insights
Cefamandole and ampicillin penetration into rabbit cerebrospinal fluid increased during meningitis. However, cefamandole levels only exceeded the inhibitory concentration for Haemophilus influenzae at the highest dose.
Area of Science:
- Pharmacology
- Infectious Diseases
- Neuroscience
Background:
- Cerebrospinal fluid (CSF) penetration is crucial for antibiotics treating central nervous system infections.
- Cefamandole and ampicillin are commonly used antibiotics, but their efficacy in meningitis depends on CSF concentrations.
Purpose of the Study:
- To evaluate the penetration of cefamandole and ampicillin into the CSF of rabbits with and without pneumococcal meningitis.
- To determine if meningitis affects antibiotic concentrations in the CSF and serum.
Main Methods:
- Rabbits were administered varying intramuscular doses of cefamandole (25-150 mg/kg) and ampicillin (200-300 mg/kg).
- CSF and serum antibiotic concentrations were measured in normal rabbits and those with experimentally induced pneumococcal meningitis (24 and 48 hours post-infection).
Main Results:
- In normal rabbits, only high-dose cefamandole (150 mg/kg) and ampicillin achieved detectable CSF concentrations.
- Meningitis significantly increased cefamandole and ampicillin penetration into the CSF after 24 hours.
- Cefamandole CSF levels exceeded the inhibitory concentration for Haemophilus influenzae only at the 150 mg/kg dose.
- Serum concentrations of both antibiotics were lower (32-38%) in rabbits with meningitis compared to normal rabbits.
Conclusions:
- Meningitis enhances cefamandole and ampicillin penetration into rabbit CSF, but therapeutic levels, especially for cefamandole against H. influenzae, may not always be achieved.
- Reduced serum concentrations in infected animals warrant further investigation regarding dosing strategies.
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