gemifloxacin and Meningitis--Pneumococcal

In experimental rabbit meningitis, gemifloxacin penetrated inflamed meninges well (22 to 33%) and produced excellent bactericidal activity (change in log(10) [Deltalog(10)] CFU/ml/h, -0.68 +/- 0.30 [mean and standard deviation]), even superior to that of the standard regimen of ceftriaxone plus vancomycin (-0.49 +/- 0.09 deltalog(10) CFU/ml/h), in the treatment of meningitis due to a penicillin-resistant pneumococcal strain (MIC, 4 mg/liter). Even against a penicillin- and quinolone-resistant strain, gemifloxacin showed good bactericidal activity (-0.48 +/- 0.16 deltalog(10) CFU/ml/h). The excellent antibacterial activity of gemifloxacin was also confirmed by time-kill assays over 8 h in vitro.

Topics: 4-Quinolones; Animals; Anti-Infective Agents; Cerebrospinal Fluid; Disease Models, Animal; Drug Resistance, Bacterial; Fluoroquinolones; Gemifloxacin; Humans; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Naphthyridines; Penicillin Resistance; Rabbits; Streptococcus pneumoniae; Treatment Outcome

In a rabbit model of Streptococcus pneumoniae meningitis, 5 mg of gemifloxacin mesylate (SB-265805) per kg/h reduced the bacterial titers in cerebrospinal fluid (CSF) almost as rapidly as 10 mg of ceftriaxone per kg/h (Deltalog CFU/ml/h +/- standard deviation [SD], -0.25 +/- 0.09 versus -0.38 +/- 0.11; serum and CSF concentrations of gemifloxacin were 2.1 +/- 1.4 mg/liter and 0.59 +/- 0.38 mg/liter, respectively, at 24 h). Coadministration of 1 mg of dexamethasone per kg did not affect gemifloxacin serum and CSF levels (2.7 +/- 1.4 mg/liter and 0.75 +/- 0.34 mg/liter, respectively, at 24 h) or activity (Deltalog CFU/ml/h +/- SD, -0.26 +/- 0.11).

Topics: Animals; Anti-Infective Agents; Ceftriaxone; Cephalosporins; Cerebrospinal Fluid; Disease Models, Animal; Fluoroquinolones; Gemifloxacin; Hippocampus; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Naphthyridines; Neurons; Rabbits; Streptococcus pneumoniae