In vitro response to bactericidal activity of cell wall-active antibiotics does not support the general opinion that enterococci are naturally tolerant to these antibiotics.

The incidence of tolerance and paradoxical response to bactericidal activity of penicillin was investigated in 50 clinical isolates of Enterococcus faecalis. Of the isolates tested, 86% exhibited the paradoxical phenomenon whereby there were more survivors at high than at low concentrations above the MIC. Low penicillin concentrations caused decreases equal to or higher than 99.9% in 11 strains, from 99.9 to 99.5% in 23 strains, and lower than 99.5% in 9 strains. Of the total strains, 14% were killed to the same extent by all concentrations above the MIC. The bactericidal activities of other beta-lactams (ampicillin and piperacillin) and other cell wall inhibitors (vancomycin and daptomycin) were also tested against some of these strains. In general, beta-lactams exhibited the best bactericidal activity at 2 x MIC. Piperacillin was the most active, as at 2 x MIC it reduced the original inoculum by 99.9% or more in most of the strains. No concentration of vancomycin above the MIC caused 99.9% killing of the strains, whereas daptomycin was bactericidal at 8 x MIC in most cases. Paradoxical response to bactericidal activity of beta-lactams was abolished by incubation of the inoculum with 2 x MIC before exposure to higher antibiotic concentrations. These findings suggest that enterococci are not always tolerant to cell wall-active antibiotics and that accurate in vitro bactericidal tests may be useful for the choice of appropriate therapy for infections caused by these microorganisms.