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2019 OMIG Abstract

Beta-adrenergic Blocking Agents Have Antifungal Activity Against Fusarium Isolates at Concentrations Similar to Levels Used to Treat Glaucoma

Ruina Bao2, Christiaan A. Rees, PhD2, N. Venkatesh Prajna, DO, DNB, FRCO4, Lalitha Prajna, MD, DNB4,
K Dharmalingam, MSc, PhD4, Kevin Fuller, PhD3, Robert Cramer2, Michael E. Zegans, MD1,2
1Dept of Surgery (Ophthalmology), 2Dept of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH; 3Dept of Ophthalmology, OUHSC, Oklahoma City, OK; 4AMRF, Aravind Madurai, Tamil Nadu, India

Purpose: Since the 1978 FDA approval of natamycin, there have been no additional, antifungal agents approved for fungal keratitis. Likewise, the recent MUTT study found that topical natamycin was superior to topical voriconazole for fungal keratitis. Thus, there remain limited options for the treatment of fungal keratitis. Towards the goal of expanding antifungal agents suitable for the treatment of keratitis, we screened medications for antifungal activity against Fusarium species, which might be appropriate for the ocular surface.

Methods: The in vitro activities of two antifungal drugs in combination with non-antifungal ophthalmic agents were evaluated using a broth microdilution method and a collection of eight Fusarium ocular isolates that exhibited resistance to both natamycin (MICs, 14 to 32 g/ml) and voriconazole (MICs, 4 to >128 g/ml). Several beta-adrenergic blocking agents were evaluated for intrinsic anti-fungal activity. An additional 10 Fusarium Indian isolates from the Mycotic Ulcer Treatment Trial (MUTT).

Results: Synergistic and indifferent interactions were observed for natamycin, voriconazole, and timolol dependent on the Fusarium isolates tested. Propranolol was tested and found to inhibit Fusarium germination and growth in vitro with MICs ranging from 31.25 ug/mL125 ug/mL. Notably, both the less cardio-active R(+) and more cardio-active S(-) isomers of propranolol demonstrated a similar antifungal effect. Results were similar between US and Indian Fusarium isolates.

Conclusion: Beta-adrenergic blocking agents have anti-fungal activity against the corneal pathogen Fusarium. Timolol has synergy with natamycin and voriconazole while propranolol has intrinsic anti-Fusarium activity. These effects were observed at concentrations that are achievable on the ocular surface and cornea. Further investigation is warranted.

Disclosure: S



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