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A. Lozinski, E. Banin, E. Berenshtein, M. Chevion, P. E. Greenberg, E. Banin; Gallium-Desferrioxamine Enhances Antibiotic Treatment in Rabbit Model of Pseudomonas Keratitis. Invest. Ophthalmol. Vis. Sci. 2007;48(13):724.
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Pseudomonas aeruginosa is an opportunistic bacterial pathogen capable of causing severe corneal infections. Formation of biofilms may be one of its principal pathogenic features, contributing to resistance against antibiotic treatment and the host immune response. Recent data suggests that iron may play an important role in the formation and stability of Pseudomonas biofilms. Our objective was to evaluate whether modulation of iron and delivery of gallium using gallium-desferrioxamine (Ga/DFO) complexes could be useful in the treatment of Pseudomonas keratitis.
Keratitis was induced in the eyes of 53 NZW rabbits by corneal scarification followed by application of contact lenses contaminated by P. aeruginosa. Once a 3.6-4mm2 infiltrate and an 8.0-8.4mm2 epithelial erosion formed, topical treatment with eye drops was initiated with eyes randomly assigned to one of five treatment groups: sham, 0.5% gentamicin (GM) alone, 0.5% GM+3 mg/ml Ga/DFO, 0.5% GM+DFO or 0.5% GM+GaCl3. Drops were administered according to an intensive regimen, similar to that used clinically, for 96 hours. Progression of the infiltrate and epithelial defect were quantified in a masked fashion from digital color and fluorescein photographs up to two weeks following infection, and extent of corneal opacification, iris injection and hypopion formation were also graded.
In sham-treated keratitis eyes, infection spread rapidly. Within 48 hours total opacification of the cornea occurred, and endophthalmitis developed in most cases. In all GM-treated groups the course of disease was less severe, with the most significant rescue occurring in the Gm+Ga/DFO-treated eyes. Infiltrate, erosion and final scar areas in these eyes were reduced by approximately 50% compared to GM alone, a difference which was statistically significant. Addition of either DFO or GaCl3 to GM yielded an effect that did not differ significantly from GM alone, with DFO+GM somewhat better than GM alone and GaCl3+GM slightly worse. Ga/DFO+GM eyes also demonstrated marked reduction in corneal opacification, iris injection and hypopion formation.
Addition of the Ga/DFO complex to GM significantly improves corneal healing of P.aeruginosa-induced keratitis. Modulation of iron availability and delivery of gallium may be a novel means to augment efficacy of antibiotic treatment.
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