Mercier Renee-Claude, Stumpo Carmine, Rybak Michael J
Anti-Infective Research Laboratory, Department of Pharmacy Services, Detroit Receiving Hospital/University Health Center, Detroit, MI 48201, USA.
J Antimicrob Chemother. 2002 Jul;50(1):19-24. doi: 10.1093/jac/dkf058.
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.
奥利万星（LY333328）是一种新型糖肽类抗生素，对革兰氏阳性菌具有活性，如耐甲氧西林金黄色葡萄球菌和耐万古霉素屎肠球菌。我们比较了pH值和生长阶段对奥利万星和万古霉素针对耐甲氧西林金黄色葡萄球菌以及对万古霉素敏感和耐药的屎肠球菌活性的影响。采用杀菌曲线法评估生长阶段（稳定期与对数期）和pH值（6.4、7.4和8.0）的影响。所有实验均使用10(6) cfu/mL的接种物。金黄色葡萄球菌和对万古霉素敏感的屎肠球菌的生长阶段不影响奥利万星的杀菌速率和活性。与稳定期相比，当屎肠球菌处于对数生长期时，奥利万星对耐万古霉素屎肠球菌菌株的杀菌速率明显更快，24小时时cfu/mL的降低幅度明显更大（P < 0.05）。在对数生长期，耐万古霉素菌株在0.6 +/- 0.01小时内达到99.9%的杀菌率，而在稳定期，奥利万星在24小时内未使接种物减少99.9%。奥利万星对金黄色葡萄球菌和对万古霉素敏感的屎肠球菌的活性不受所测试的pH条件影响。当在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菌活性显著增强（P < 0.05）。我们的研究表明，在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，如在感染性心内膜炎中所见，或当生物体暴露于酸性环境时，奥利万星对处于稳定生长期的耐万古霉素屎肠球菌菌株的活性可能会降低。
