Efficacy of gatifloxacin alone and in combination with cefepime against penicillin-resistant Streptococcus pneumoniae in a rabbit meningitis model and in vitro.
Gatifloxacin penetrated well into cerebrospinal fluid (CSF) (49 +/- 11%), measured by comparison of AUC(CSF)/AUC(serum), and showed good bactericidal activity (leading to a decrease of 0.75 +/- 0.17 log10 cfu/mL/h) in the treatment of experimental meningitis in rabbits caused by a penicillin-resistant pneumococcal strain (MIC 4 mg/L). It was significantly more effective than the standard regimen, ceftriaxone with vancomycin, which led to a decrease of 0.53 +/- 0.17 log10 cfu/mL/h. The addition of cefepime to gatifloxacin slightly improved the killing rates (giving a decrease of 0.84 +/- 0.14 log10 cfu/mL/h). In vitro, synergy was demonstrated between cefepime and gatifloxacin by the chequerboard method (fractional inhibitory concentration index = 0.5) and by viable counts over 8 h.
Perrig
M
M
Department of Internal Medicine, Zieglerspital, 3007 Berne, Switzerland.
Acosta
F
F
Cottagnoud
M
M
Gerber
C M
CM
Täuber
M G
MG
Cottagnoud
P
P
D000818:Animals; D000890:Anti-Infective Agents / Q000134:cerebrospinal fluid / Q000627:therapeutic use*; D000077723:Cefepime; D002511:Cephalosporins / Q000134:cerebrospinal fluid / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D024841:Fluoroquinolones; D000077734:Gatifloxacin; D016920:Meningitis, Bacterial / Q000188:drug therapy* / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D010403:Penicillin Resistance; D011817:Rabbits; D013296:Streptococcus pneumoniae / Q000187:drug effects; D016896:Treatment Outcome
D000890:Anti-Infective Agents; D002511:Cephalosporins; D024841:Fluoroquinolones; D000077723:Cefepime; D000077734:Gatifloxacin