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Comparative therapeutic efficacy of clinafloxacin in a pneumococcal meningitis mouse model
M A Shapiro1, K D Donovan, J W Gage
1Department of Infectious Diseases, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, MI 48105, USA.
Abstract:
The therapeutic efficacy of clinafloxacin, a fluoroquinolone in clinical trials, was compared with that of ciprofloxacin and ceftriaxone in a novel pneumococcal meningitis mouse model. Mice were challenged by the intracerebral ventricular route with 50 IL of a lethal bacterial suspension and treated subcutaneously 2 h later. Both penicillin-susceptible and multidrug-resistant pneumococcal strains were used for evaluation. Survival percentages were calculated as the median curative dose (CD50) using log-probit statistical methods. Ceftriaxone was the most active agent against the penicillin-susceptible strain (CD50 = 2 mg/kg), but showed a 30-fold decrease in potency against the resistant strain. Clinafloxacin was equally effective against both strains, and proved to be the most active agent against the penicillin-resistant pneumococcus.
Insights
Clinafloxacin demonstrated superior efficacy in a novel pneumococcal meningitis mouse model, proving effective against both susceptible and resistant strains. This fluoroquinolone offers a promising therapeutic option for pneumococcal meningitis.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Pneumococcal meningitis remains a significant global health challenge.
- Emergence of multidrug-resistant Streptococcus pneumoniae necessitates novel therapeutic strategies.
- Fluoroquinolones are a class of antibiotics with broad-spectrum activity.
Purpose of the Study:
- To evaluate the therapeutic efficacy of clinafloxacin against pneumococcal meningitis.
- To compare clinafloxacin with established antibiotics, ciprofloxacin and ceftriaxone.
- To assess efficacy against both penicillin-susceptible and multidrug-resistant pneumococcal strains.
Main Methods:
- Development of a novel mouse model for pneumococcal meningitis.
- Intracerebral ventricular challenge with Streptococcus pneumoniae.
- Subcutaneous administration of therapeutic agents (clinafloxacin, ciprofloxacin, ceftriaxone).
- Calculation of median curative dose (CD50) using log-probit analysis.
Main Results:
- Ceftriaxone was most potent against penicillin-susceptible strains (CD50 = 2 mg/kg).
- Ceftriaxone potency decreased 30-fold against resistant strains.
- Clinafloxacin exhibited equal efficacy against both susceptible and resistant strains.
- Clinafloxacin demonstrated superior activity against multidrug-resistant pneumococcus.
Conclusions:
- Clinafloxacin is a highly effective therapeutic agent for pneumococcal meningitis.
- Clinafloxacin maintains efficacy against multidrug-resistant Streptococcus pneumoniae.
- Clinafloxacin represents a promising treatment option for resistant pneumococcal meningitis.