Besifloxacin ophthalmic suspension in patients with bacterial keratitis: A prospective, randomized clinical study

RON JANS CLINICAL CORNEA RESEARCH AWARD WINNER 

Authors: Fatma Zaguia, Michael Ross, Mahshad Darvish, Jean Deschênes
Author Disclosure Block: F. Zaguia: None. M. Ross: None. M. Darvish: Allergan, Johnson & Johnson, Santen, Shire. J. Deschênes: AbbVie, Allergan, Imprimis, NIE/NEI, Santen. Shire.

Abstract Body:

Purpose: Bacterial keratitis is a serious ocular problem that can, if not appropriately treated, lead to corneal scarring, perforation, endophthalmitis, and ultimately blindness. Current accepted treatment by most ophthalmologists for corneal ulcers involves aggressive therapy with fortified antibiotics typically every hour, around the clock dosing for at least the 48 hours, causing significant distress to patients, as well as compliance issues. Finally, delayed epithelial healing rate and conjunctival/corneal toxicity are known side effects of fortified antibiotics. Besifloxacin ophthalmic suspension is a novel topical fluoroquinolone, specifically developed as an ocular topical preparation. Several in vitro studies have shown a higher potency when compared with earlier fluoroquinolones, however there is limited data about its safety and efficacy in the treatment of bacterial keratitis.

Study Design: Our study is a multi-site prospective, randomised trial to determine if besifloxacin when compared to fortified tobramycin/vancomycin drops results in non-inferior clinical resolution of bacterial keratitis. Primary outcome was clinical resolution at day 28: no evidence of active bacterial infection, complete reepithelialization/wound healing and resolved inflammation.

Methods: Patients with bacterial ulcers larger than 1 mm were randomised to receive besifloxacin at initially Q4H dosing vs fortified tobramycin + vancomycin at initial Q1H dosing. Complete exams were recorded at initial visit, and at predetermined subsequent visits.

Results: Overall, there were no treatment failures in the besifloxacin group. There was no statistical difference between groups when controlled for initial infiltrate size, with average infiltrate size of 1.2mm in besifloxacin group vs 2mm in fortified group (p=0.11). Median number of days taken for the ulcer to heal between the besifloxacin group (12 days) and fortified group (19 days) showed no statistical difference (p=0.4). The group treated with besifloxacin showed a statistically significant more rapid epithelialization rate, at a mean of 4 days vs 11 (p=0.01). Improvement of visual acuity from baseline at presentation showed no statistical difference (p=0.49) with approximately 1.2 lines gained on Snellen chart for besifloxacin group vs 2 lines of improvement in fortified group.

Conclusions: Our preliminary results failed to find a difference in efficacy of besifloxacin, a novel fluoroquinolone in the treatment of bacterial keratitis when compared to traditional combination therapy of fortified antibiotics.