COMPARISON OF 4 AMINOGLYCOSIDE ANTIBIOTICS IN THERAPY OF EXPERIMENTAL ESCHERICHIA-COLI MENINGITIS

Abstract

Tobramycin, sisomicin and amikacin were compared with gentamicin in the therapy of experimental E. coli meningitis in rabbits. Meningitis was produced in 40 animals by intracisternal injection of 105 E. coli. Three dosages of each antibiotic were administered i.v. over 8 h. Serum and CSF samples were obtained at 0, 2, 4, 6 and 8 h for determination of aminoglycoside concentrations and CSF bacteria counts. The 4 aminoglycosides demonstrated comparable penetration into the CSF. The mean percent penetration with the 3 dosages was 10-50% for gentamicin, 8-23% for tobramycin, 6-16% for sisomicin and 11-23% for amikacin. This variation in penetration reflected individual differences in each dosage group and the increase in percent penetration that was observed during therapy. Sisomicin and gentamicin were consistently bactericidal in vivo. Mean CSF bacterial titers decreased 3.07 logs in rabbits treated with sisomicin and 2.44 logs in animals treated with gentamicin. Even though CSF concentrations were comparable, the group treated with tobramycin demonstrated only a 0.64 log decrease and the amikacin group had a 0.45 log increase in mean CSF titers. The bactericidal effect of sisomicin appeared to be more rapid than that of gentamicin. During the 1st 2 h of therapy CSF titers declined 1.02 logs in animals treated with sisomicin as compared to 0.37 log in animals receiving gentamicin even though gentamicin concentrations were higher (mean 7.4 vs. 4.1 g/ml). Sisomicin also demonstrated greater bactericidal activity than the other aminoglycosides in normal CSF in vitro. Sisomicin may be of value in the therapy of E. coli meningitis.