Although
penicillin tolerance has been increasingly recognized among clinical isolates of many Gram-positive organisms, the significance of this phenomenon in vivo is not clear. The present study was performed to characterize
penicillin-tolerant enterococci by several in-vitro parameters and to examine the significance in vivo in a rabbit model of
infective endocarditis. Tolerant enterococci exhibited several characteristics which distinguished them from non-tolerant bacteria: significantly greater ratios of MIC to MBC of penicillin, resistance to
penicillin-induced lysis and killing, and growth in areas of superinhibitory concentrations of
penicillin upon transfer from
penicillin gradient to
penicillin-free plates. In-vivo studies of aortic valve
endocarditis in rabbits treated with
procaine penicillin G (300 mg/kg/day) revealed strikingly different responses between
infections due to one tolerant and one non-tolerant strain. Animals infected with a tolerant enterococcus showed consistently greater bacterial counts in vegetations during ten days of
therapy and significantly lower rates of vegetation sterilization. Serum
penicillin levels were not significantly different between the two groups, but serum bactericidal titres were significantly lower for the tolerant than for the non-tolerant strains. These findings indicate that
penicillin tolerance identified by several in-vitro criteria is a significant determinant of the in-vivo response of enterococci to
penicillin therapy.