Baltch A L, Smith R P, Ritz W J, Bopp L H
Stratton Veterans Affairs Medical Center and Albany Medical College, Albany, New York 12208, USA.
Antimicrob Agents Chemother. 1998 Oct;42(10):2564-8. doi: 10.1128/AAC.42.10.2564.
One hundred ninety-five individual vancomycin-resistant Enterococcus faecium (VRE) isolates from five upstate New York hospitals were studied for antimicrobial susceptibilities to LY333328, quinupristin-dalfopristin, 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 the postantibiotic effects (PAE) of LY333328 and ampicillin were evaluated. In microdilution tests, the MIC of LY333328 at which 90% of the isolates were inhibited (MIC90) was 2 microg/ml in Mueller-Hinton II (MH II) broth and 1 microg/ml in brain heart infusion (BHI) broth. In contrast, on MH II agar the MIC90 was 4 microg/ml and on BHI agar it was >16 microg/ml. Bactericidal activity was observed for most strains at concentrations from 8 to >/=133 times the MIC of the tube macrodilution in MH II broth. A bactericidal effect of LY333328 plus ampicillin was demonstrated in time-kill studies, but there was great strain-to-strain variability. By the MH II agar dilution method, bacteristatic synergy (defined as a fractional inhibitory concentration 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 MIC). However, 50% normal pooled human serum decreased the PAE to 12.2 h at 10 times the MIC. Test conditions and media had a considerable effect on VRE susceptibilities to LY333328. The prolonged PAE of LY333328, a potent new bactericidal glycopeptide, and its synergy with ampicillin in a large proportion of strains suggest that further evaluation of this drug in pharmacokinetic studies and experimental infections, including those with VRE, is warranted.
对从纽约州北部五家医院分离出的195株耐万古霉素屎肠球菌（VRE）进行了研究，以检测它们对LY333328、奎奴普丁-达福普汀、替考拉宁、氨苄西林和庆大霉素的抗菌敏感性。LY333328是针对VRE活性最强的抗生素。评估了培养基和方法对LY333328抗菌活性、其与氨苄西林的协同作用以及LY333328和氨苄西林的抗生素后效应（PAE）的影响。在微量稀释试验中，90%的分离株被抑制时LY333328的最低抑菌浓度（MIC90）在Mueller-Hinton II（MH II）肉汤中为2μg/ml，在脑心浸液（BHI）肉汤中为1μg/ml。相比之下，在MH II琼脂上MIC90为4μg/ml，在BHI琼脂上>16μg/ml。在MH II肉汤中，大多数菌株在浓度为试管常量稀释法MIC的8至≥133倍时观察到杀菌活性。在时间-杀菌研究中证明了LY333328加氨苄西林的杀菌作用，但菌株间差异很大。通过MH II琼脂稀释法，61%的受试菌株显示出与LY333328和氨苄西林的抑菌协同作用（定义为分数抑菌浓度<0.5）。在类似条件下，分别有27%和15%的受试菌株显示出与LY333328和奎奴普丁-达福普汀或庆大霉素的协同作用。LY333328的PAE延长（在10倍MIC时为23.0小时）。然而，50%的正常人混合血清将10倍MIC时的PAE降至12.2小时。试验条件和培养基对VRE对LY333328的敏感性有相当大的影响。强效新型杀菌糖肽LY333328延长的PAE及其在很大一部分菌株中与氨苄西林的协同作用表明，有必要在药代动力学研究和实验性感染（包括VRE感染）中对该药物进行进一步评估。
