Gentamicin increases the efficacy of vancomycin against penicillin-resistant pneumococci in the rabbit meningitis model.
In experimental meningitis a single dose of gentamicin (10 mg/kg of body weight) led to gentamicin levels in around cerebrospinal fluid (CSF) of 4 mg/liter for 4 h, decreasing slowly to 2 mg/liter 4 h later. The CSF penetration of gentamicin ranged around 27%, calculated by comparison of areas under the curve (AUC in serum/AUC in CSF). Gentamicin monotherapy (-1.24 log(10) CFU/ml) was inferior to vancomycin monotherapy (-2.54 log(10) CFU/ml) over 8 h against penicillin-resistant pneumococci. However, the combination of vancomycin with gentamicin was significantly superior (-4.48 log(10) CFU/ml) compared to either monotherapy alone. The synergistic activity of vancomycin combined with gentamicin was also demonstrated in vitro in time-kill assays.
Cottagnoud
Philippe
P
Department of Internal Medicine, Inselspital, 3010 Bern, Switzerland. pcottagn@insel.ch
Gerber
Cynthia M
CM
Cottagnoud
Marianne
M
Täuber
Martin G
MG
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000627:therapeutic use*; D005839:Gentamicins / Q000627:therapeutic use*; D008586:Meningitis, Pneumococcal / Q000188:drug therapy*; D010403:Penicillin Resistance / Q000502:physiology; D011817:Rabbits; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome; D014640:Vancomycin / Q000627:therapeutic use*
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D014640:Vancomycin