Effects of EDP-420 on penicillin-resistant and quinolone- and penicillin-resistant pneumococci in the rabbit meningitis model.

Abstract

OBJECTIVES:

To test the efficacy of EDP-420, a new ketolide, in experimental pneumococcal meningitis and to determine its penetration into the CSF.

METHODS:

The experimental rabbit model was used in this study and EDP-420 was tested against a penicillin-resistant and a penicillin- and quinolone-resistant mutant. EDP-420 was also tested against both strains in time-killing assays over 8 h in vitro.

RESULTS:

In experimental meningitis, EDP-420 produced a bactericidal activity comparable to the standard regimen based on a combination of vancomycin with ceftriaxone against a penicillin-resistant Streptococcus pneumoniae and a penicillin- and quinolone-resistant S. pneumoniae isolate. The penetration of EDP-420 into inflamed meninges was 38% after an i.v. injection of 10 mg/kg. The bactericidal activity of EDP-420 was also confirmed in in vitro time-killing assays.

CONCLUSIONS:

EDP-420 is an efficacious alternative treatment in pneumococcal meningitis, especially when resistant strains are suspected.

• Authors: Armin Stucki, Peter Gerber, Fernando Acosta, Marianne Cottagnoud, Philippe Cottagnoud, Lijiang Jiang, Phong Nguyen, Derek Wachtel, Guoqiang Wang, Ly T Phan
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 61 Issue 3 Pg. 665-9 (Mar 2008) ISSN: 1460-2091 [Electronic] England
• PMID: 18222952 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bridged-Ring Compounds
• EDP 420
• Macrolides
• Penicillins
• Quinolones

Topics

• Animals
• Bridged-Ring Compounds (pharmacology, therapeutic use)
• Disease Models, Animal
• Macrolides (pharmacology, therapeutic use)
• Meningitis, Bacterial (blood, drug therapy)
• Penicillin Resistance (drug effects, physiology)
• Penicillins (pharmacology, therapeutic use)
• Quinolones (pharmacology, therapeutic use)
• Rabbits
• Streptococcus pneumoniae (drug effects, physiology)