Ocular Microbiology and Immunology Group
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2020 OMIG Abstract

The Search for Antifungal Prophylaxis Following Artificial Cornea Surgery —
An In Vitro Study

Sarah Kim, BA^1,3, Paulo J.M. Bispo, PhD^2,3, Eden E.L. Tanner, DPhil⁴, Samir Mitragotri, PhD⁴,
Rafaella N. e Silva, MD, PhD^1,3, Ilene Gipson, PhD^3,5, James Chodosh, MD, MPH^1,2,3,
Irmgard Behlau, MD^6,7, Eleftherios I. Paschalis, PhD^1,3, Michael S. Gilmore, PhD^2,3,
and Claes H. Dohlman, MD, PhD^1,3
1The Boston Keratoprosthesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA; ²Infectious Disease Institute, Massachusetts Eye & Ear, Harvard Medical School, Boston, MA; ³Harvard Medical School, Boston, MA; ⁴John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA; ⁵Schepens Eye Research Institute, Massachusetts Eye & Ear, Harvard Medical School, Boston, MA; ⁶Molecular Biology and Microbiology and Ophthalmology, Tufts Graduate School of Biomedical Sciences, Tufts University School of Medicine, Boston, MA;
⁷Infectious Diseases, Mount Auburn Hospital, Harvard Medical School, Cambridge, MA

Methods: Several commonly used antibiotics for antimicrobial prophylaxis following artificial cornea implantation in addition to antiseptics [benzalkonium chloride (BAK), povidone-iodine (PI), and some ionic liquids (ILs)] were tested in vitro against Candida albicans, Fusarium solani, and Aspergillus fumigatus. Time kill activity was determined. Toxicity was assayed in vitro on human corneal epithelial cultures using Trypan Blue. Adhesion and tissue invasion experiments were also carried out on porcine corneas and commonly used contact lenses, with or without gamma-irradiation, and by analysis with fluorescent microscopy.

Results: Polymyxin B (PMB)/trimethoprim (TMP)/ BAK (Polytrim^®), PMB alone, gatifloxacin (GAT) with BAK (Zymaxid^®), and same-concentration BAK alone, exhibited antifungal activity in vitro. Moxifloxacin (MOX) or GAT without BAK, as well as TMP, vancomycin (VAN), and chloramphenicol (CHL), had no effect. 1% PI and ILs had the highest efficacy/toxicity ratios (>1), and Polytrim^® was species dependent. Sub-fungicidal concentrations of Polytrim^® reduced adhesion of Candida albicans to Kontur^TM contact lenses. Gamma-irradiated corneas showed resistance to fungal invasion.

Conclusion: Of antibiotics already in use for bacterial prophylaxis after KPro surgery, Polytrim^® is a commonly used antibiotic with antifungal effects mediated by both PMB and BAK, and may be sufficient for prophylaxis. PI as a 1% solution appears to be promising as a long-term antifungal. Choline-undecanoate IL is effective and virtually non-toxic, and warrants further development.

Disclosure: E

Support: The B-KPro Research Fund

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