Antimicrobial activities of ceragenins against clinical isolates of resistant Staphylococcus aureus
Antimicrobial activities of ceragenins against clinical isolates of resistant Staphylococcus aureus
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DOI：
10.1128/aac.01325-06
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发表时间：
2007-04-01
影响因子：
4.9
通讯作者：
Savage, Paul B.
中科院分区：
文献类型：
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作者：
Chin, Judy N.;Rybak, Michael J.;Savage, Paul B.
金黄色葡萄球菌分离株中糖肽耐药率的上升令人担忧，并强调了开发新型有效化合物的必要性。Ceragenins CSA-8和CSA-13是模拟内源性抗菌肽的阳离子类固醇分子，先前已被证明对多重耐药细菌具有广谱活性。我们检测了CSA-8和CSA-13对万古霉素中间体S临床分离株的活性。金黄色葡萄球菌（VISA）、异质性万古霉素中间体S.金黄色葡萄球菌（hVISA），以及万古霉素耐药的S.并与达托霉素、利奈唑胺、万古霉素进行药敏试验和杀灭曲线分析。我们还检查了CSA-13的浓度依赖性活性、接种物效应、抗生素后效应（PAE）以及与各种抗菌剂组合的协同作用。总体而言，CSA-13的MIC和最低杀菌浓度比CSA-8低四倍。VRSA、VISA和hVISA临床分离株的时间-杀灭曲线分析证明了浓度依赖性杀菌作用。当使用更高的起始细菌密度时，也观察到接种物效应，在6-log（10）-CFU/ml的起始接种物下，达到99.9%杀灭所需的时间达到1小时，而在10倍MIC的8-至9-log（10）-CFU/ml的起始接种物下，达到99.9%杀灭所需的时间>= 24小时（P
The rise in the rates of glycopeptide resistance among Staphylococcus aureus isolates is concerning and underscores the need for the development of novel potent compounds. Ceragenins CSA-8 and CSA-13, cationic steroid molecules that mimic endogenous antimicrobial peptides, have previously been demonstrated to possess broad-spectrum activities against multidrug-resistant bacteria. We examined the activities of CSA-8 and CSA-13 against clinical isolates of vancomycin-intermediate S. aureus (VISA), heterogeneous vancomycin-intermediate S. aureus (hVISA), as well as vancomycin-resistant S. aureus (VRSA) and compared them to those of daptomycin, linezolid, and vancomycin by susceptibility testing and killing curve analysis. We also examined CSA-13 for its concentration-dependent activity, inoculum effect, postantibiotic effect (PAE), and synergy in combination with various antimicrobials. Overall, the MICs and minimal bactericidal concentrations of CSA-13 were fourfold lower than those of CSA-8. Time-kill curve analysis of the VRSA, VISA, and hVISA clinical isolates demonstrated concentration-dependent bactericidal killing. An inoculum effect was also observed when a higher starting bacterial density was used, with the time required to achieve 99.9% killing reaching 1 h with a 6-log(10)-CFU/ml starting inoculum, whereas it was >= 24 h with a 8- to 9-log(10)-CFU/ml starting inoculum with 10x the MIC (P