Evaluation of cefepime alone and in combination with vancomycin against penicillin-resistant pneumococci in the rabbit meningitis model and in vitro.
Cefepime, a broad-spectrum, fourth-generation cephalosporin, showed excellent CSF penetration with levels ranging between 10 and 16 mg/L after two intravenous injections (100 mg/kg). The bactericidal activity of cefepime (-0.60 +/- 0.28 Deltalog(10) cfu/mL/h) was superior to that of ceftriaxone (-0.34 +/- 0.23 Deltalog(10) cfu/mL/h, P < 0.05) and vancomycin (-0.39 +/- 0.19 Deltalog(10) cfu/mL/h, P < 0.05) in the treatment of rabbits with meningitis caused by an isolate highly resistant to penicillin (MIC of penicillin G: 4 mg/L). The addition of vancomycin to both cephalosporins did not significantly increase the killing rate compared with monotherapies (P > 0.05). Similar results were obtained in time-killing experiments in vitro.
Gerber
C M
CM
Department of Internal Medicine, Inselspital, 3010 Berne. Department of Internal Medicine, Zieglerspital, 3007 Berne, Switzerland.
Cottagnoud
M
M
Neftel
K
K
Täuber
M G
MG
Cottagnoud
P
P
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D000077723:Cefepime; D002443:Ceftriaxone / Q000494:pharmacology / Q000627:therapeutic use; D002511:Cephalosporins / Q000494:pharmacology / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination / Q000494:pharmacology / Q000627:therapeutic use*; D008586:Meningitis, Pneumococcal / Q000188:drug therapy*; D010403:Penicillin Resistance; D011817:Rabbits; D014640:Vancomycin / Q000494:pharmacology / Q000627:therapeutic use*
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D014640:Vancomycin; D002443:Ceftriaxone; D000077723:Cefepime