Db. Hoellman et al., ACTIVITIES AND TIME-KILL STUDIES OF SELECTED PENICILLINS, BETA-LACTAMASE INHIBITOR COMBINATIONS, AND GLYCOPEPTIDES AGAINST ENTEROCOCCUS-FAECALIS, Antimicrobial agents and chemotherapy, 42(4), 1998, pp. 857-861
The activities of piperacillin, piperacillin-tazobactam, ticarcillin,
ticarcillin-clavulanate, ampicillin, ampicillin-sulbactam, vancomycin,
and teicoplanin were tested against 212 Enterococcus faecalis strains
(9 beta-lactamase producers) by standard agar dilution MIC testing (1
0(4) CFU/spot). The MICs at which 50 and 90% of the isolates were inhi
bited (MIC(50)s and MIC(90)s, respectively) were as follows (mu g/ml):
piperacillin, 4 and 8; piperacillin-tazobactam, 4 and 8; ticarcillin,
64 and 128; ticarcillin-clavulanate, 64 and 128; ampicillin, 2 and 2;
ampicillin-sulbactam, 1 and 2; vancomycin, 1 and 4; and teicoplanin,
0.5 and 1. Agar dilution MIC testing of the nine beta-lactamase-positi
ve strains with an inoculum of 10(6) CFU/spot revealed higher beta-lac
tam MICs (piperacillin, 64 to >256 mu g/ml; ticarcillin, 128 to >256 m
u g/ml; and ampicillin, 16 to 128 mu g/ml); however, MICs with the add
ition of inhibitors were similar to those obtained with the lower inoc
ulum. Time-kill studies of 15 strains showed that piperacillin-tazobac
tam was bactericidal (99.9% killing) for 14 strains after 24 h at four
times the MIC, with 90% killing of all 15 strains at two times the MI
C. After 12 and 6 h, 90% killing of 14 and 13 strains, respectively, w
as found at two times the MIC. Ampicillin gave 99.9% killing of 14 bet
a-lactamase-negative strains after 24 h at eight times the MIC, with 9
0% killing of all 15 strains at two times the MIC. After 12 and 6 h, 9
0% killing of 14 and 13 strains, respectively, was found at two times
the MIC. Killing by ticarcillin-clavulanate was slower than that obser
ved for piperacillin-tazobactam, relative to the MIC. For the one beta
-lactamase-producing strain tested by time-kill analysis with a higher
inoculum, addition of the three inhibitors (including sulbactam) to e
ach of the beta-lactams resulted in bactericidal activity at 24 h at t
wo times the MIC. For an enzyme-negative strain, addition of inhibitor
s did not influence kinetics. Kinetics of vancomycin and teicoplanin w
ere significantly slower than those of the beta-lactams, with bacteric
idal activity against 6 strains after 24 h at eight times the MIC, wit
h 90% killing of 12 and 14 strains, respectively, at four times the MI
C. Slower-kill kinetics by both glycopeptides were observed at earlier
periods.