COMPARISON OF INHIBITORY AND BACTERICIDAL ACTIVITIES AND POSTANTIBIOTIC EFFECTS OF LY333328 AND AMPICILLIN USED SINGLY AND IN COMBINATION AGAINST VANCOMYCIN-RESISTANT ENTEROCOCCUS-FAECIUM
Al. Baltch et al., COMPARISON OF INHIBITORY AND BACTERICIDAL ACTIVITIES AND POSTANTIBIOTIC EFFECTS OF LY333328 AND AMPICILLIN USED SINGLY AND IN COMBINATION AGAINST VANCOMYCIN-RESISTANT ENTEROCOCCUS-FAECIUM, Antimicrobial agents and chemotherapy, 42(10), 1998, pp. 2564-2568
One hundred ninety-five individual vancomycin-resistant Enterococcus f
aecium (VRE) isolates from five upstate New York hospitals were studie
d for antimicrobial susceptibilities to LY333328, quinupristin-dalfopr
istin, teicoplanin, ampicillin, and gentamicin. LY333328 was the most
active antibiotic against VRE, The effect of media and methods on the
antibacterial activity of LY333328, its synergy with ampicillin, and t
he postantibiotic effects (PAE) of LY333328 and ampicillin were evalua
ted. In microdilution tests, the MIC of LY333328 at which 90% of the i
solates were inhibited (MIC90) was 2 mu g/ml in Mueller-Hinton II (MII
II) broth and I mu g/ml in brain heart infusion (BIII) broth. In cont
rast, on MII II agar the MIC90 was 4 mu g/ml and on BIII agar it was >
16 mu g/ml. Bactericidal activity was observed for most strains at con
centrations from 8 to greater than or equal to 133 times the MIC of th
e tube macrodilution in MII II broth. A bactericidal effect of LY33332
8 plus ampicillin was demonstrated in time-kill studies, but there was
great strain-to-strain variability. By the MII II agar dilution metho
d, bacteristatic synergy (defined as a fractional inhibitory concentra
tion of <0.5) with LY333328 and ampicillin was demonstrated for 61% of
the strains tested. Under similar conditions, there was synergy with
LY333328 and quinupristin-dalfopristin or gentamicin for 27 and 15% of
the strains tested, respectively. The PAE of LY333328 was prolonged (
23.0 h at 10 times the MIG). However, 50% normal pooled human ser um d
ecreased the PAE to 12.2 h at 10 times the MIG. Test conditions and me
dia had a considerable effect on VRE susceptibilities to LY333328, The
prolonged PAE of LY333328, a potent new bactericidal glycopeptide, an
d its synergy with ampicillin in a large proportion of strains suggest
that further evaluation of this drug in pharmacokinetic studies and e
xperimental infections, including those with VRE, is warranted.