Effect of growth phase and pH on the in vitro activity of a new glycopeptide, oritavancin (LY333328), against Staphylococcus aureus and Enterococcus faecium
Effect of growth phase and pH on the in vitro activity of a new glycopeptide, oritavancin (LY333328), against Staphylococcus aureus and Enterococcus faecium
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DOI：
10.1093/jac/dkf058
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发表时间：
2002-07-01
影响因子：
5.2
通讯作者：
Rybak, MJ
中科院分区：
文献类型：
--
作者：
Mercier, RC;Stumpo, C;Rybak, MJ
Oritavancin (LY333328) 是一种新型糖肽，具有对抗革兰氏阳性菌（如耐甲氧西林金黄色葡萄球菌和耐万古霉素屎肠球菌）的活性。我们比较了 pH 值和生长阶段对奥利万星和万古霉素对抗甲氧西林金黄色葡萄球菌和万古霉素敏感且耐药的屎肠球菌活性的影响。杀伤曲线方法用于评估生长期（稳态与指数）和 pH（6.4、7.4 和 8.0）的影响。所有实验均使用 10(6) cfu/mL 的接种量。金黄色葡萄球菌和万古霉素敏感的屎肠球菌的生长阶段不影响奥利万星的速率和杀伤活性。与静止期相比，奥利万星对耐万古霉素屎肠球菌的杀灭速度明显加快，24 h cfu/mL 下降幅度明显更大（P < 0.05）。在指数生长期，万古霉素抗性菌株在 0.6 +/- 0.01 小时内实现 99.9% 杀灭，而在稳定生长期，奥利万星在 24 小时内并未将接种量减少 99.9%。奥利万星针对金黄色葡萄球菌和万古霉素敏感的屎肠球菌的活性不受测试的 pH 条件影响。在pH 7.4和8.0下测试时，奥利万星对耐万古霉素屎肠球菌菌株的杀灭活性显着增强（P < 0.05）。我们的研究表明，当针对金黄色葡萄球菌和屎肠球菌敏感菌株进行测试时，奥利万星的活性似乎不受生物体生长阶段或环境 pH 值的影响。然而，奥利万星对处于静止生长期的耐万古霉素屎肠球菌菌株的活性可能会降低，如感染性心内膜炎或当生物体暴露于酸性环境时所见。
Oritavancin (LY333328) is a novel glycopeptide with activity against Gram-positive bacteria such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium. We compared the effects of pH and growth phase on the activity of oritavancin and vancomycin against methicillin-resistant S. aureus and vancomycin-susceptible and -resistant E. faecium. Killing curve methods were used to evaluate the effect of growth phase (stationary versus exponential) and pH (6.4, 7.4 and 8.0). An inoculum of 10(6) cfu/mL was used for all experiments. Growth phase of S. aureus and vancomycin-susceptible E. faecium did not influence the rate and killing activity of oritavancin. The rate of killing by oritavancin against the vancomycin-resistant E. faecium strain was significantly faster and the reduction in cfu/mL at 24 h was significantly greater when the organism was in exponential compared with stationary growth phase (P < 0.05). In exponential growth phase, time to 99.9% killing was achieved in 0.6 +/- 0.01 h for the vancomycin-resistant strain, whereas in stationary growth phase, oritavancin did not decrease the inoculum by 99.9% within 24 h. Oritavancin's activity against S. aureus and vancomycin-susceptible E. faecium was not influenced by the pH conditions tested. Oritivancin's killing activity against the vancomycin-resistant E. faecium strain was significantly enhanced when tested at pH 7.4 and 8.0 (P < 0.05). Our study has demonstrated that oritavancin's activity does not seem to be influenced by the growth phase of the organisms or the pH of the environment when tested against sensitive strains of S. aureus and E. faecium. However, oritavancin's activity might be reduced against vancomycin-resistant E. faecium strains in stationary growth phase, as seen in infective endocarditis or when organisms are exposed to an acidic environment.