Pharmacokinetics and efficacy of ceftazidime in experimental Haemophilus influenzae b meningitis
1Department of Pediatrics, The University of Texas Health Science Center at Dallas, Southwestern Medical School, USA.
Abstract:
Ceftazidime is active in vitro against Haemophilus influenzae. When given to infant rats in a dose of 25 mg/kg ceftazidime achieved a mean peak blood concentration of 31.8 mg/l and a mean trough concentration at 3 h of 25 mg/l during steady state. Blood half-life of ceftazidime was 1.3 h. Mean CSF penetration of ceftazidime was 22.8% of blood levels, independent of the presence or absence of meningitis. Infant rats with meningitis due to beta-lactamase negative and beta-lactamase positive H. influenzae strains had decreased CSF bacterial counts 8 h after a single 25 mg/kg dose and, without additional therapy, 45% of animals maintained negative cultures.
Insights
Ceftazidime effectively treats infant rat meningitis caused by Haemophilus influenzae. This antibiotic achieved therapeutic blood and cerebrospinal fluid concentrations, reducing bacterial counts and maintaining negative cultures in 45% of cases.
Area of Science:
- Pharmacology and Microbiology
- Pediatric Infectious Diseases
Background:
- Haemophilus influenzae is a significant cause of bacterial meningitis in infants.
- Ceftazidime is a third-generation cephalosporin with known activity against Gram-negative bacteria.
Purpose of the Study:
- To evaluate the pharmacokinetic profile of ceftazidime in infant rats.
- To assess the efficacy of ceftazidime in treating experimental infant rat meningitis caused by Haemophilus influenzae.
Main Methods:
- Infant rats received a single intravenous dose of ceftazidime (25 mg/kg).
- Blood and cerebrospinal fluid (CSF) concentrations were measured over time.
- CSF bacterial counts were assessed 8 hours post-dose in animals with meningitis.
Main Results:
- Ceftazidime achieved a mean peak blood concentration of 31.8 mg/l and a half-life of 1.3 hours.
- Mean CSF penetration was 22.8% of blood levels, irrespective of meningitis status.
- A single dose reduced CSF bacterial counts, with 45% of treated rats maintaining negative cultures.
Conclusions:
- Ceftazidime demonstrates favorable pharmacokinetics and significant in vivo activity against Haemophilus influenzae meningitis in infant rats.
- These findings support the potential utility of ceftazidime in treating pediatric meningitis caused by this pathogen.
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