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2020 OMIG Abstract

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

Sarah Kim, BA1,3, Paulo J.M. Bispo, PhD2,3, Eden E.L. Tanner, DPhil4, Samir Mitragotri, PhD4,
Rafaella N. e Silva, MD, PhD1,3, Ilene Gipson, PhD3,5, James Chodosh, MD, MPH1,2,3,
Irmgard Behlau, MD6,7, Eleftherios I. Paschalis, PhD1,3, Michael S. Gilmore, PhD2,3,
and Claes H. Dohlman, MD, PhD1,3

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

Purpose: To evaluate the antifungal properties of topical antibiotics (already being used successfully to prevent bacterial endophthalmitis) as well as some promising antiseptics for antifungal prophylaxis in the setting of artificial cornea implantation.

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 KonturTM 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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