Bactericidal activity of gentamicin against Enterococcus faecalis in vitro and in vivo

Abstract

The activity of gentamicin at various concentrations against two strains of Enterococcus faecalis was investigated in vitro and in a rabbit model of aortic endocarditis. In vitro, gentamicin at 0.5 to 4 times the MIC failed to reduce the number of bacteria at 24 h. Rabbit or human serum dramatically increased gentamicin activity, leading to a >/=3-log(10) CFU/ml decrease in bacterial counts when the drug concentration exceeded the MIC. Susceptibility testing in the presence of serum was predictive of in vivo activity, since gentamicin alone significantly reduced the number of surviving bacteria in the vegetations if the peak-to-MIC ratio was greater than 1. However, gentamicin selected resistant mutants in rabbits. The intrinsic activity of gentamicin should be taken into account in evaluation of combinations of gentamicin and cell wall-active agents against enterococci.

FIG. 1

In vitro activity of gentamicin (Gent) against E. faecalis JH2-2 and BM4281 in BHI (a), 50% BHI and 50% rabbit serum (b), or 50% BHI and 50% human serum (c). Gentamicin concentrations are expressed in micrograms per milliliter.

FIG. 2

Activity of gentamicin in experimental endocarditis due to E. faecalis. Reductions of bacterial counts in the vegetations were plotted for different peak-to-MIC ratios of gentamicin.