Potential synergy activity of the novel ceragenin, CSA-13, against clinical isolates of Pseudomonas aeruginosa, including multidrug-resistant P. aeruginosa
Potential synergy activity of the novel ceragenin, CSA-13, against clinical isolates of Pseudomonas aeruginosa, including multidrug-resistant P. aeruginosa
复制标题
DOI：
10.1093/jac/dkm457
复制
发表时间：
2008-02-01
影响因子：
5.2
通讯作者：
Rybak, Michael J.
中科院分区：
文献类型：
--
作者：
Chin, Judy N.;Jones, Ronald N.;Rybak, Michael J.
目的：我们先前的研究数据表明，新的ceragenin，CSA-13，对耐糖肽金黄色葡萄球菌表现出浓度依赖性的杀菌活性。然而，尚不清楚CSA-13是否对铜绿假单胞菌表现出类似的性质。我们评估CSA-13 antipseudomonal活性相比，头孢吡肟，美罗培南，哌拉西林/他唑巴坦，妥布霉素和环丙沙星的敏感性测试，以及结合头孢吡肟，妥布霉素和ciprofloxacin.Methods：50临床分离的铜绿假单胞菌进行了分析，参考肉汤微量稀释法。使用10（6）cfu/mL的初始接种物，在0.5x、1x、2x和4x MIC下通过时间-杀灭曲线（TKC）分析评价了具有不同亲和性的4种菌株。对于协同作用测试，进行CSA-13单独和与头孢吡肟、妥布霉素和环丙沙星在0.5x MIC下组合的TKC分析。TKC分析证明了浓度依赖性活性，CSA-13在4x MIC下在1小时达到最早的杀灭（99.9%，检测限）。联合TKC分析表明与头孢吡肟和环丙沙星的协同作用或相加作用，在某些情况下实现早期协同作用。CSA-13中加入妥布霉素后，对两株铜绿假单胞菌的杀灭效果无差异。结论：CSA-13对临床分离的铜绿假单胞菌，包括多重耐药铜绿假单胞菌，具有浓度依赖性。头孢吡肟或环丙沙星添加到CSA-13增强细菌杀灭，实现早期协同作用。
Objectives: Previous data from our research had shown that the novel ceragenin, CSA-13, demonstrated concentration-dependent bactericidal activity against glycopeptide-resistant Staphylococcus aureus. However, it is unknown whether CSA-13 demonstrates a similar property against Pseudomonas aeruginosa. We evaluated CSA-13 antipseudomonal activity compared with cefepime, meropenem, piperacillin/tazobactam, tobramycin and ciprofloxacin by susceptibility testing as well as in combination with cefepime, tobramycin and ciprofloxacin.Methods: Fifty clinical isolates of P. aeruginosa were analysed by reference broth microdilution methods. Four strains with various susceptibilities were evaluated by time-killing curve (TKC) analysis at 0.5x, 1x, 2x and 4x MIC using an initial inoculum of 10(6) cfu/mL. For synergy testing, TKC analysis of CSA-13 alone and in combination with cefepime, tobramycin and ciprofloxacin at 0.5x MIC was performed.Results: CSA-13 MIC50 and MBC50 were 16 and 16 mg/L, respectively. TKC analysis demonstrated concentration-dependent activity, with CSA-13 at 4x MIC achieving earliest kill at 1 h (99.9%, detection limit). Combination TKC analysis demonstrated synergy or additive effect with cefepime and ciprofloxacin, in some cases achieving early synergy. The addition of tobramycin to CSA-13 resulted in no difference in kill for two strains.Conclusions: CSA-13 showed concentration-dependent activity against clinical isolates of P. aeruginosa, including multidrug-resistant P. aeruginosa. The addition of cefepime or ciprofloxacin to CSA-13 enhanced bacterial kill, achieving early synergy.