Topical Linezolid in Streptococcus Pneumoniae Corneal Ulcer Model in Rabbits

Abstract

Abstract: : Purpose: Linezolid is effective against many gram positive bacteria including vancomycin resistant enterococcus (VRE). We wish to determine if topical linezolid is effective in the treatment of Streptococcus Pneumoniae corneal ulcers in a rabbit model. Methods: After the rabbits were sedated and given topical proparacaine, 0.05 cc of S. Pneumoniae (∼1 X 10⁶ CFU) was injected into the corneal stroma of 20 eyes of 20 New Zealand white rabbits making a 3 mm circular infiltration. The epithelium over the area of infection was abraded with a 3.0mm slit knife. Eyes in which inadvertent corneal perforation occurred were excluded. A total of 16 eyes were randomly assigned to one of three treatment groups: 6 eyes received 4mg/ml of linezolid, 6 eyes received 25mg/ml of vancomycin, and 4 eyes received saline. The drops were administered topically every 20 minutes for 8 hours. The animals were sacrificed. 5 mm corneal buttons were trephined for consistency in specimen size among subjects. The corneas were dissected using a blade then homogenized with tissue grinders. The homogenate was cultured via calibrated spiral plating and incubated at 37°C and 5% CO₂ on blood agar plates. Colony forming unit (CFU) were counted after incubation for 36 and 54 hours. Discharge, tearing, and corneal exudates were rated on each rabbit on a scale of 1–5 before and after treatment. Results: The average number of colonies in the linezolid group was 3/ul ± 2.1; Vancomycin 94/ul ± 107; saline 109/ul ± 56. The Wilxocon Signed–rank test for the symptoms listed above showed for the linezolid group W=28 with R=1; vancomycin W=27 with R=0.9286; saline W=6 with R=1. Discharge decreased by 76% with linezolid, 56% with vancomycin, and 0% with saline. Tearing decreased by 76% with linezolid, 68% with vancomycin, and 40% with saline. Corneal exudates decreased by 47% with linezolid, 44% with vancomycin, and 40% with saline. Conclusions: While this is a pilot study and further research in needed, it is clear that topical linezolid was at least as effective in reducing CFUs as vancomycin in this rabbit model of S. Pneumoniae corneal ulcer. Discharge, tearing and corneal exudates were markedly improved in the linezolid group versus the vancomycin group. Linezolid appeared to be better tolerated than vancomycin topically.

Keywords: antibiotics/antifungals/antiparasitics • bacterial disease • cornea: epithelium