Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Istanbul University, Turkey.
Chemotherapy. 2011;57(6):505-10. doi: 10.1159/000335588. Epub 2012 Jan 27.
The rise in the rates of antibiotic resistance among Pseudomonas aeruginosa strains from cystic fibrosis (CF) patients is concerning and underscores the need for the development of novel compounds. Among them CSA-13, a cationic steroid molecule, mimics the activity of naturally occurring antimicrobial peptides.
MICs and MBCs were determined using the microbroth dilution technique. Combinations were assessed using the checkerboard technique. The bactericidal activity of CSA-13 in combination with colistin was measured using the time-kill curve method for two strains.
The MIC(90) values of CSA-13, colistin, tobramycin, and ciprofloxacin were 2, 1, 1, and 2 mg/l, respectively. The MBCs were equal to or two-fold greater than those of the MICs. With a fractional inhibitory concentration index of ≤0.5 as borderline, synergistic interactions were mostly seen with the CSA-13-colistin combination (54%). No antagonism was observed. The results of the time-kill curve analysis demonstrated rapid bactericidal activity of CSA-13 and synergism with colistin; in one strain early synergy was achieved.
CSA-13 appears to be a good candidate in the treatment of P. aeruginosa strains in CF patients. Future studies should be performed to correlate the safety, efficacy, and pharmacokinetic parameters of this molecule.
囊性纤维化 (CF) 患者中铜绿假单胞菌菌株的抗生素耐药率上升令人担忧，这突显了开发新型化合物的必要性。其中 CSA-13 是一种阳离子甾体分子，模拟天然存在的抗菌肽的活性。
使用微量肉汤稀释技术测定 MIC 和 MBC。使用棋盘技术评估组合。使用时间杀伤曲线法测量 CSA-13 与多粘菌素联合使用对两种菌株的杀菌活性。
CSA-13、多粘菌素、妥布霉素和环丙沙星的 MIC(90) 值分别为 2、1、1 和 2 mg/l。MBC 等于或大于 MIC 的两倍。以 0.5 作为临界值，当分数抑制浓度指数≤0.5 时，CSA-13-多粘菌素联合用药主要表现出协同作用（54%）。未观察到拮抗作用。时间杀伤曲线分析的结果表明 CSA-13 具有快速杀菌活性，并与多粘菌素协同作用；在一种菌株中，早期协同作用得以实现。
CSA-13 似乎是 CF 患者治疗铜绿假单胞菌菌株的一个有前途的候选药物。未来的研究应将该分子的安全性、疗效和药代动力学参数相关联。
