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

Stucki, Armin ; Gerber, Peter ; Acosta, Fernando ; Cottagnoud, Marianne ; Cottagnoud, Philippe ; Jiang, Lijiang ; Nguyen, Phong ; Wachtel, Derek ; Wang, Guoqiang ; Phan, Ly T.

In: Journal of Antimicrobial Chemotherapy, 2008, vol. 61, no. 3, p. 665-669

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    Titre
    • Effects of EDP-420 on penicillin-resistant and quinolone- and penicillin-resistant pneumococci in the rabbit meningitis model
    Auteur
    • Stucki, Armin. Department of Internal Medicine, Inselspital, Bern, Switzerland
    • Gerber, Peter. Clinic of Pneumology, Inselspital, Bern, Switzerland
    • Acosta, Fernando. Clinic of Internal Medicine, Spital Bern-Ziegler, Bern, Switzerland
    • Cottagnoud, Marianne. Clinic of Internal Medicine, Spital Bern-Ziegler, Bern, Switzerland
    • Cottagnoud, Philippe. Department of Internal Medicine, Inselspital, Bern, Switzerland
    • Jiang, Lijiang. Enanta Pharmaceuticals, Inc., Watertown, MA, USA
    • Nguyen, Phong. Enanta Pharmaceuticals, Inc., Watertown, MA, USA
    • Wachtel, Derek. Enanta Pharmaceuticals, Inc., Watertown, MA, USA
    • Wang, Guoqiang. Enanta Pharmaceuticals, Inc., Watertown, MA, USA
    • Phan, Ly T.. Enanta Pharmaceuticals, Inc., Watertown, MA, USA
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Journal of Antimicrobial Chemotherapy, 2008, vol. 61, no. 3, p. 665-669. Oxford University Press
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:296010
    Summary
    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 iv 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