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Trovafloxacin in combination with vancomycin against penicillin-resistant pneumococci in the rabbit meningitis model
D Rodoni1, F Hänni, C M Gerber
1Department of Internal Medicine, Inselspital, Berne, Switzerland.
Abstract:
Trovafloxacin, a new fluoroquinolone, produced bactericidal activity (-0.33 +/- 0.13 delta log10 CFU/ml.h; intravenously [i.v.] administered dose, 15 mg/kg) comparable to that of vancomycin (-0.39 +/- 0.18 delta log10 CFU/ml.h; i.v. admininistered dose, 20 mg/kg) in the treatment of experimental meningitis in rabbits due to a pneumococcal strain highly resistant to penicillin (MIC of penicillin G, 4 micrograms/ml). The combination of both drugs significantly increased (P < 0.05) the killing rate (-0.60 +/- 0.23 delta log10 CFU/ml.h) compared to that produced by either monotherapy. These results were also confirmed in vitro.
Insights
Trovafloxacin and vancomycin show comparable bactericidal activity against penicillin-resistant pneumococcal meningitis in rabbits. Combining these antibiotics significantly enhances killing rates, offering a promising therapeutic strategy.
Area of Science:
- Pharmacology
- Infectious Diseases
- Microbiology
Background:
- Pneumococcal meningitis poses a significant threat, especially with increasing antibiotic resistance.
- Penicillin-resistant Streptococcus pneumoniae strains necessitate alternative treatment options.
- Fluoroquinolones represent a class of antibiotics with broad-spectrum activity.
Purpose of the Study:
- To evaluate the efficacy of trovafloxacin compared to vancomycin in treating experimental pneumococcal meningitis in rabbits.
- To investigate the synergistic effect of combining trovafloxacin and vancomycin against resistant pneumococcal strains.
- To assess the in vitro bactericidal activity of both monotherapies and their combination.
Main Methods:
- Experimental meningitis was induced in rabbits using a penicillin-resistant pneumococcal strain.
- Intravenous administration of trovafloxacin (15 mg/kg) and vancomycin (20 mg/kg) as monotherapies.
- Evaluation of bactericidal activity using delta log10 CFU/ml.h measurements.
- In vitro susceptibility testing and time-kill assays were performed.
Main Results:
- Trovafloxacin demonstrated comparable bactericidal activity to vancomycin in vivo.
- The combination therapy significantly increased the killing rate compared to monotherapy (P < 0.05).
- In vitro studies corroborated the enhanced bactericidal effect of the drug combination.
Conclusions:
- Trovafloxacin is a viable therapeutic option for experimental meningitis caused by penicillin-resistant pneumococci.
- Combination therapy with trovafloxacin and vancomycin offers enhanced efficacy.
- These findings support further investigation into combination antimicrobial strategies for resistant bacterial meningitis.