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H. Zhu, T. Z. Oo, N. Cole, M. D. P. Willcox; Lactoferricin Acts Synergistically With Antimicrobials Against Ocular Isolates of Pseudomonas aeruginosa and Can Help to Treat Keratitis. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2393.
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Pseudomonas aeruginosa is the major cause of contact lens-related microbial keratitis. This bacterium has become increasingly resistant to antibiotic therapy. The aims of the study were to evaluate the ability of bovine lactoferricin (LFcin B) to increase susceptibility of P. aeruginosa to a range ofantimicrobials in vitro, and the possibility of using LFcin B as an adjunct to antibiotics in treatment of corneal infection in vivo.
Eight P. aeruginosa ocular isolates including Paer1, 6294, 6206 and five multi-drug resistance strains (Paer31, -32, -33, -35, & -37) were used in the study. Checkerboard synergism test was performed to investigate the combined effects of LFcin B and the antibiotics ciprofloxacin, ceftazidime and gentamicin against test strains in vitro. Corneas of 6-8 week old C57B1/6 mice were topically challenged with resistance strain P. aeruginosa 37 and then randomly divided into 4 treatment groups (20 mice per group). Nine hours post-challenge mice were treated topically hourly for 8 hours with vehicle (PBS), LFcin B (2.5 mg/mL), commercially available ciprofloxacin ophthalmic drops, or ciprofloxacin drops containing LFcin B (2.5 mg/ml). Mice were then clinically examined and sacrificed, and bacterial numbers in corneas were enumerated.
There was synergy or partial synergy between LFcin B and ciprofloxacin or ceftazidime in all five resistant strains of P. aeruginosa, with MIC values reduced by 4-fold for ciprofloxacin and up to 8-fold for ceftazidime. There was no synergistic effect seen between LFcin B and gentamicin for any strain. The macroscopic ocular response was significantly less severe in the mice treated with ciprofloxacin in combination with LFcin B compared to mice treated with PBS (p < 0.012). Mice treated with the combination of ciprofloxacin/LFcin B significantly improved scores for density of infiltration of the cornea and showed a reduction in corneal epithelial defect compared to control and ciprofloxacin alone groups. Treatment with either ciprofloxacin/LFcin B or ciprofloxacin alone resulted in significantly decreased bacterial numbers compared to other treatments (p < 0.001).
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