Synergy between trovafloxacin and ceftriaxone against penicillin-resistant pneumococci in the rabbit meningitis model and in vitro.
The bactericidal activities of monotherapy with trovafloxacin (-0.37 +/- 0.15 Delta log(10) CFU/ml. h), vancomycin (-0.32 +/- 0.12 Delta log(10) CFU/ml. h), and ceftriaxone (-0.36 +/- 0.19 Delta log(10) CFU/ml. h) for the treatment of experimental meningitis in rabbits due to a clinical penicillin-resistant pneumococcal strain (MIC, 4 mg/liter) were similar. The combination of ceftriaxone with trovafloxacin considerably improved the killing rates (-0.67 +/- 0.16 Delta log(10) CFU/ml. h) and was slightly superior to ceftriaxone with vancomycin (killing rate, -0.53 +/- 0. 22 Delta log(10) CFU/ml. h), the regimen most commonly used in clinical practice. In vitro, synergy was demonstrated between ceftriaxone and trovafloxacin by the checkerboard method (fractional inhibitory concentration index, 0.5) and by time-killing assays over 8 h.
Cottagnoud
P
P
Department of Internal Medicine, Inselspital, Bern, Switzerland. pcottagn@insel.ch
Acosta
F
F
Cottagnoud
M
M
Neftel
K
K
Täuber
M G
MG
D000818:Animals; D000890:Anti-Infective Agents / Q000134:cerebrospinal fluid / Q000494:pharmacology / Q000627:therapeutic use*; D002443:Ceftriaxone / Q000134:cerebrospinal fluid / Q000494:pharmacology / Q000627:therapeutic use*; D002511:Cephalosporins / Q000134:cerebrospinal fluid / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D024841:Fluoroquinolones; D008586:Meningitis, Pneumococcal / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000382:microbiology; D008826:Microbial Sensitivity Tests; D009287:Naphthyridines / Q000134:cerebrospinal fluid / Q000494:pharmacology / Q000627:therapeutic use*; D010403:Penicillin Resistance; D011008:Pneumococcal Infections / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000382:microbiology; D011817:Rabbits; D013296:Streptococcus pneumoniae / Q000187:drug effects
D000890:Anti-Infective Agents; D002511:Cephalosporins; D024841:Fluoroquinolones; D009287:Naphthyridines; D002443:Ceftriaxone; C080163:trovafloxacin