Brien Holden Vision Institute, Sydney, New South Wales, Australia.
J Antimicrob Chemother. 2010 Jun;65(6):1243-51. doi: 10.1093/jac/dkq106. Epub 2010 Apr 7.
The objectives of this study were to determine whether a synergistic effect could be obtained in vitro between bovine lactoferricin (B-LFcin) and antibiotics against Pseudomonas aeruginosa and Staphylococcus aureus isolates from ocular infections, and to evaluate the use of B-LFcin as an adjunct to the antibiotic treatment of corneal infection in vivo.
Chequerboard and time-kill assays were performed to investigate the combined effects of B-LFcin and conventional antibiotics, including ciprofloxacin, ceftazidime and gentamicin, against 17 strains of P. aeruginosa (8) and S. aureus (9) isolated from ocular infection and inflammation, and 1 reference strain of S. aureus. Corneas of C57BL/6 mice were topically challenged with a multidrug-resistant strain of P. aeruginosa. Nine hours post-challenge, mice were treated topically and hourly with either vehicle, B-LFcin, ciprofloxacin or ciprofloxacin containing B-LFcin for 8 h. Corneas were then clinically examined, and bacterial numbers and levels of myeloperoxidase (MPO) evaluated.
Synergy between B-LFcin and ciprofloxacin or ceftazidime was identified in most P. aeruginosa isolates, including multidrug-resistant strains, whereas no synergistic effect was seen between B-LFcin and gentamicin. Synergy was only observed with B-LFcin and ciprofloxacin against 2/10 S. aureus strains, and there was no synergy between B-LFcin and any of the other antibiotics tested. Combined B-LFcin and ciprofloxacin treatment significantly improved the clinical outcome, and reduced bacterial numbers and MPO in infected mouse corneas. B-LFcin alone was also able to reduce levels of MPO in infected corneas.
These findings indicate that B-LFcin may have advantages as an adjunct therapy with both antimicrobial and anti-inflammatory properties in the treatment of corneal infection.
本研究旨在确定牛乳铁蛋白（B-LFcin）与抗生素联合应用是否对眼部感染分离的铜绿假单胞菌和金黄色葡萄球菌具有协同作用，并评估 B-LFcin 作为辅助治疗角膜感染的体内应用。
采用棋盘微量稀释法和时间杀伤试验，检测 B-LFcin 与临床常用抗生素（环丙沙星、头孢他啶和庆大霉素）联合应用对 17 株眼部感染和炎症分离的铜绿假单胞菌（8 株）和金黄色葡萄球菌（9 株），以及 1 株金黄色葡萄球菌标准株的协同作用。采用多药耐药铜绿假单胞菌对 C57BL/6 小鼠角膜进行局部攻击。攻毒 9 小时后，局部和每小时用载体、B-LFcin、环丙沙星或含 B-LFcin 的环丙沙星对小鼠进行 8 小时治疗。然后对角膜进行临床检查，评估细菌数量和髓过氧化物酶（MPO）水平。
在大多数铜绿假单胞菌分离株（包括多药耐药株）中发现 B-LFcin 与环丙沙星或头孢他啶联合具有协同作用，而与庆大霉素联合无协同作用。B-LFcin 与环丙沙星仅对 10 株金黄色葡萄球菌分离株中的 2 株具有协同作用，与其他测试的抗生素均无协同作用。联合 B-LFcin 和环丙沙星治疗可显著改善临床结果，减少感染小鼠角膜中的细菌数量和 MPO。单独使用 B-LFcin 也能降低感染角膜中的 MPO 水平。
这些发现表明，B-LFcin 可能具有优势，作为一种辅助治疗药物，具有抗菌和抗炎特性，用于治疗角膜感染。
