Grepafloxacin against penicillin-resistant pneumococci in the rabbit meningitis model.
Grepafloxacin, a new fluoroquinolone, produced bactericidal activity comparable to that of vancomycin and ceftriaxone in the treatment in rabbits of meningitis caused by a pneumococcal strain highly resistant to penicillin (MIC 4 mg/L) (triangle uplog(10) cfu/mL*h for grepafloxacin, -0.32 +/- 0.15; dose, 15 mg/kg iv; triangle uplog(10) cfu/mL*h for vancomycin, -0.39 +/- 0.18; dose, 2 x 20 mg/kg iv; triangle uplog(10) cfu/mL*h for ceftriaxone, -0.32 +/- 0. 12; dose, 125 mg/kg iv). Higher doses of grepafloxacin (30 mg/kg and 2 x 50 mg/kg) did not improve the killing rates. The combination of grepafloxacin with vancomycin was not significantly superior to monotherapies (P > 0.05). In vitro, grepafloxacin was bactericidal at concentrations above the MIC. Using concentrations around the MIC, addition of vancomycin to grepafloxacin showed synergic activity.
Gerber
C M
CM
Department of Internal Medicine, Zieglerspital, Berne, Switzerland.
Tovar
L
L
Cottagnoud
M
M
Neftel
K A
KA
Täuber
M G
MG
Cottagnoud
P
P
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics / Q000494:pharmacology*; D024841:Fluoroquinolones; D008586:Meningitis, Pneumococcal / Q000382:microbiology*; D008826:Microbial Sensitivity Tests; D010403:Penicillin Resistance; D010879:Piperazines / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics / Q000494:pharmacology*; D011817:Rabbits; D013296:Streptococcus pneumoniae / Q000187:drug effects*; D014640:Vancomycin / Q000494:pharmacology; D020713:Vancomycin Resistance
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D010879:Piperazines; D014640:Vancomycin; C075375:grepafloxacin