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Antimicrobial therapy of experimental meningitis caused by Streptococcus pneumoniae strains with different
Abstract:
The pharmacokinetics and bacteriological efficacies of penicillin G, ceftriaxone, vancomycin, and imipenem were determined in rabbits with experimental meningitis caused by Streptococcus pneumoniae strains with different penicillin susceptibilities. Drug dosages were adjusted to attain peak concentrations in serum that were similar to those observed in infants and children. In animals infected with a penicillin-susceptible (MBC, 0.008 micrograms/ml) pneumococcus, penicillin G and ceftriaxone reduced the number of organisms in cerebrospinal fluid (CSF) by greater than or equal to 4.14 log10 CFU/ml after single doses and after 9-h continuous infusions. A single large dose (50 mg/kg) of penicillin G was comparatively ineffective (-2.15 log10 CFU/ml) against a relatively penicillin-resistant (MBC, 0.5 micrograms/ml) strain, whereas ceftriaxone therapy resulted in a 3.66- and 4.77-log10 CFU/ml reduction after single doses and 9-h continuous infusions, respectively. In animals in which meningitis was caused by a penicillin-resistant (MBC, 8.0 micrograms/ml) pneumococcus, a single dose of penicillin (50 or 150 mg/kg) or of ceftriaxone failed to lower the number of organisms in CSF. Vancomycin and imipenem reduced the counts in CSF by at least 2.19 and 4.10 log10 CFU/ml after single doses and 9-h infusions, respectively. In all experiments, a bactericidal titer of greater than or equal to 1:8 in CSF was necessary to achieve a maximal bacteriological effect.
Insights
Penicillin G and ceftriaxone show varying efficacy against Streptococcus pneumoniae meningitis in rabbits, with ceftriaxone proving more effective against resistant strains. Optimal treatment requires specific drug concentrations and bactericidal titers in cerebrospinal fluid (CSF).
Area of Science:
- Pharmacology
- Microbiology
- Infectious Diseases
Background:
- Bacterial meningitis remains a significant global health challenge, particularly in pediatric populations.
- Streptococcus pneumoniae is a leading cause of bacterial meningitis, with increasing antimicrobial resistance posing treatment difficulties.
- Understanding the pharmacokinetic and bacteriological efficacies of various antibiotics is crucial for optimizing meningitis treatment strategies.
Purpose of the Study:
- To evaluate the pharmacokinetics and bacteriological efficacy of penicillin G, ceftriaxone, vancomycin, and imipenem in a rabbit model of Streptococcus pneumoniae meningitis.
- To assess the impact of different penicillin susceptibilities of S. pneumoniae strains on antibiotic effectiveness.
- To determine the necessary cerebrospinal fluid (CSF) bactericidal titer for maximal antimicrobial effect.
Main Methods:
- Experimental meningitis was induced in rabbits using Streptococcus pneumoniae strains with varying penicillin minimum bactericidal concentrations (MBCs).
- Antibiotic dosages were adjusted to achieve human-relevant peak serum concentrations.
- Bacteriological efficacy was assessed by measuring the reduction inlog10 colony-forming units per milliliter (CFU/ml) in CSF after single doses and continuous infusions.
Main Results:
- Penicillin G and ceftriaxone demonstrated significant efficacy against penicillin-susceptible S. pneumoniae strains, reducing CSF organism counts by over 4 log10 CFU/ml.
- Ceftriaxone showed superior efficacy compared to penicillin G against penicillin-resistant strains, achieving substantial reductions in CSF bacterial load.
- Vancomycin and imipenem exhibited bactericidal activity against resistant strains, with imipenem demonstrating greater efficacy.
- A CSF bactericidal titer of ≥1:8 was identified as necessary for maximal bacteriological effect across all tested antibiotics.
Conclusions:
- Ceftriaxone is a promising therapeutic option for penicillin-resistant pneumococcal meningitis, offering better outcomes than penicillin G.
- Vancomycin and imipenem provide alternative treatment options for meningitis caused by resistant S. pneumoniae strains.
- Achieving adequate drug penetration into the CSF and maintaining a sufficient bactericidal titer are critical for successful treatment of pneumococcal meningitis.