Chin Judy N, Jones Ronald N, Sader Helio S, Savage Paul B, Rybak Michael J
Anti-infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI 48201, USA.
J Antimicrob Chemother. 2008 Feb;61(2):365-70. doi: 10.1093/jac/dkm457. Epub 2007 Dec 12.
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.
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.
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.
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.
我们之前的研究数据表明，新型杀菌肽CSA - 13对耐糖肽金黄色葡萄球菌具有浓度依赖性杀菌活性。然而，尚不清楚CSA - 13对铜绿假单胞菌是否具有类似特性。我们通过药敏试验以及与头孢吡肟、妥布霉素和环丙沙星联合使用，评估了CSA - 13对铜绿假单胞菌的抗菌活性，并与头孢吡肟、美罗培南、哌拉西林/他唑巴坦、妥布霉素和环丙沙星进行了比较。
采用参考肉汤微量稀释法分析50株铜绿假单胞菌临床分离株。使用10(6) cfu/mL的初始接种量，通过时间杀菌曲线（TKC）分析，在0.5倍、1倍、2倍和4倍最低抑菌浓度（MIC）下对4株不同敏感性的菌株进行评估。对于协同试验，对单独的CSA - 13以及与头孢吡肟、妥布霉素和环丙沙星在0.5倍MIC下联合使用进行TKC分析。
CSA - 13的MIC50和MBC50分别为16 mg/L和16 mg/L。TKC分析显示其具有浓度依赖性活性，CSA - 13在4倍MIC时最早在1小时达到杀菌效果（99.9%，检测限）。联合TKC分析显示与头孢吡肟和环丙沙星具有协同或相加作用，在某些情况下实现了早期协同。将妥布霉素添加到CSA - 13中，对两株菌株的杀菌效果没有差异。
CSA - 13对铜绿假单胞菌临床分离株，包括多重耐药铜绿假单胞菌，表现出浓度依赖性活性。将头孢吡肟或环丙沙星添加到CSA - 13中可增强杀菌效果，实现早期协同。
