1 Department of Otolaryngology - Head and Neck Surgery, University of Alabama at Birmingham, Birmingham, Alabama.
2 Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama.
Am J Rhinol Allergy. 2019 Mar;33(2):129-136. doi: 10.1177/1945892418815615. Epub 2018 Dec 25.
Methods to improve the clinical efficacy of currently available antibiotics against multidrug resistant bacteria in cystic fibrosis (CF) chronic rhinosinusitis (CRS) are greatly needed. Ivacaftor, a cystic fibrosis transmembrane conductance regulator potentiator, was recently identified as having potentially beneficial off-target effects as a weak inhibitor of bacterial DNA gyrase and topoisomerase IV. The objective of the current study is to evaluate whether ivacaftor enhances the antimicrobial activity of ciprofloxacin against Pseudomonas aeruginosa.
The planktonic growth of the PAO-1 strain of P. aeruginosa was studied in the presence of ciprofloxacin and/or ivacaftor. Effects were measured according to optical density of cultured PAO-1 at 600 nm. For a static PAO-1 biofilm assay, the PAO-1 strain was inoculated and cultured for 72 h in the presence of the drugs. Formed PAO-1 biofilms were quantified by crystal violet staining and imaged with confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM).
PAO-1 growth was significantly reduced in the presence of ivacaftor (8 or 16 µg/mL) and ciprofloxacin (0.02 or 0.05 µg/mL) compared to ciprofloxacin alone ( P < .001). Similarly, ivacaftor (8 or 16 µg/mL) showed a significant reduction of PAO-1 biofilms when treated with 0.05 µg/mL of ciprofloxacin. Significant synergism was noted between ciprofloxacin and 16 µg/mL of ivacaftor ( P < .0001) in reducing planktonic growth and biofilm formation. Quantitative measurements with crystal violet staining were correlated to CLSM and SEM images.
Ivacaftor enhanced ciprofloxacin's antimicrobial activity against P. aeruginosa. Further studies evaluating the efficacy of ivacaftor/ciprofloxacin combination for P. aeruginosa for CF CRS are warranted.
迫切需要找到提高目前针对囊性纤维化（CF）慢性鼻-鼻窦炎（CRS）多重耐药菌抗生素临床疗效的方法。Ivacaftor，一种囊性纤维化跨膜电导调节剂增强剂，最近被确定具有潜在的有益的非靶点作用，作为细菌 DNA 拓扑异构酶 II 和 IV 的弱抑制剂。本研究的目的是评估 Ivacaftor 是否增强环丙沙星对铜绿假单胞菌的抗菌活性。
在环丙沙星和/或 Ivacaftor 存在的情况下，研究 PAO-1 铜绿假单胞菌的浮游生物生长。根据 600nm 培养的 PAO-1 的光密度测量效果。对于静态 PAO-1 生物膜测定，将 PAO-1 菌株接种并在药物存在下培养 72 小时。通过结晶紫染色和共聚焦激光扫描显微镜（CLSM）和扫描电子显微镜（SEM）成像定量测定形成的 PAO-1 生物膜。
与单独使用环丙沙星相比（P<0.001），Ivacaftor（8 或 16μg/ml）和环丙沙星（0.02 或 0.05μg/ml）存在时 PAO-1 生长明显减少。同样，当用 0.05μg/ml 的环丙沙星处理时，Ivacaftor（8 或 16μg/ml）也显著减少 PAO-1 生物膜。在降低浮游生物生长和生物膜形成方面，环丙沙星和 Ivacaftor（16μg/ml）之间存在显著协同作用（P<0.0001）。结晶紫染色的定量测量与 CLSM 和 SEM 图像相关。
Ivacaftor 增强了环丙沙星对铜绿假单胞菌的抗菌活性。进一步评估 Ivacaftor/环丙沙星联合治疗 CF CRS 中铜绿假单胞菌的疗效的研究是必要的。
