Effects of EDP-420 on penicillin-resistant and quinolone- and penicillin-resistant pneumococci in the rabbit meningitis model.
OBJECTIVE
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.
Stucki
Armin
A
Department of Internal Medicine, Inselspital, Bern, Switzerland.
Gerber
Peter
P
Acosta
Fernando
F
Cottagnoud
Marianne
M
Cottagnoud
Philippe
P
Jiang
Lijiang
L
Nguyen
Phong
P
Wachtel
Derek
D
Wang
Guoqiang
G
Phan
Ly T
LT
D000818:Animals; D001952:Bridged-Ring Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D018942:Macrolides / Q000494:pharmacology / Q000627:therapeutic use*; D016920:Meningitis, Bacterial / Q000097:blood / Q000188:drug therapy*; D010403:Penicillin Resistance / Q000187:drug effects* / Q000502:physiology; D010406:Penicillins / Q000494:pharmacology / Q000627:therapeutic use; D015363:Quinolones / Q000494:pharmacology / Q000627:therapeutic use*; D011817:Rabbits; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000502:physiology
D001952:Bridged-Ring Compounds; C520838:EDP 420; D018942:Macrolides; D010406:Penicillins; D015363:Quinolones