Editorial Type:
Antimicrobials

In vitro efficacy of a buffered chelating solution as an antimicrobial potentiator for antifungal drugs against fungal pathogens obtained from horses with mycotic keratitis

William L. Weinstein Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.

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Phillip A. Moore Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.

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Susan Sanchez Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.
Athens Diagnostic Laboratory, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.

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Ursula M. Dietrich Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.

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Richard E. Wooley Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.

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Branson W. Ritchie Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.

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DOI:
https://doi.org/10.2460/ajvr.67.4.562
Volume/Issue:
Volume 67: Issue 4
Online Publication Date:
01 Apr 2006
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Abstract

Objective—To determine whether a novel third-generation chelating agent (8mM disodium EDTA dehydrate and 20mM 2-amino-2-hydroxymethyl-1, 3-propanediol) would act as an antimicrobial potentiator to enhance in vitro activity of antifungal medications against fungal isolates obtained from horses with mycotic keratitis.

Sample Population—Fungal isolates (3 Aspergillus isolates, 5 Fusarium isolates, 1 Penicillium isolate, 1 Cladosporium isolate, and 1 Curvularia isolate) obtained from horses with mycotic keratitis and 2 quality-control strains obtained from the American Type Culture Collection (ATCC; Candida albicans ATCC 90028 and Paecilomyces variotii ATCC 36257).

Procedure—Minimum inhibitory concentrations (MICs) against fungal isolates for 4 antifungal drugs (miconazole, ketoconazole, itraconazole, and natamycin) were compared with MICs against fungal isolates for the combinations of each of the 4 antifungal drugs and the chelating agent. The Clinical and Laboratory Standards Institute microdilution assay method was performed by use of reference-grade antifungal powders against the fungal isolates and quality-control strains of fungi.

Results—Values for the MIC at which the antifungal drugs decreased the growth of an organism by 50% (MIC50) and 90% (MIC90) were decreased for the control strains and ophthalmic fungal isolates by 50% to 100% when the drugs were used in combination with the chelating agent at a concentration of up to 540 μg/mL.

Conclusions and Clinical Relevance—The chelating agent increased in vitro activity of antifungal drugs against common fungal pathogens isolated from eyes of horses with mycotic keratitis.

Abstract

Objective—To determine whether a novel third-generation chelating agent (8mM disodium EDTA dehydrate and 20mM 2-amino-2-hydroxymethyl-1, 3-propanediol) would act as an antimicrobial potentiator to enhance in vitro activity of antifungal medications against fungal isolates obtained from horses with mycotic keratitis.

Sample Population—Fungal isolates (3 Aspergillus isolates, 5 Fusarium isolates, 1 Penicillium isolate, 1 Cladosporium isolate, and 1 Curvularia isolate) obtained from horses with mycotic keratitis and 2 quality-control strains obtained from the American Type Culture Collection (ATCC; Candida albicans ATCC 90028 and Paecilomyces variotii ATCC 36257).

Procedure—Minimum inhibitory concentrations (MICs) against fungal isolates for 4 antifungal drugs (miconazole, ketoconazole, itraconazole, and natamycin) were compared with MICs against fungal isolates for the combinations of each of the 4 antifungal drugs and the chelating agent. The Clinical and Laboratory Standards Institute microdilution assay method was performed by use of reference-grade antifungal powders against the fungal isolates and quality-control strains of fungi.

Results—Values for the MIC at which the antifungal drugs decreased the growth of an organism by 50% (MIC50) and 90% (MIC90) were decreased for the control strains and ophthalmic fungal isolates by 50% to 100% when the drugs were used in combination with the chelating agent at a concentration of up to 540 μg/mL.

Conclusions and Clinical Relevance—The chelating agent increased in vitro activity of antifungal drugs against common fungal pathogens isolated from eyes of horses with mycotic keratitis.

Contributor Notes

Supported by the Veterinary Ophthalmology Research Fund at the University of Georgia.

Drs. Wooley and Ritchie are inventors of the antibiotic potentiator technology marketed under the name Tricide. Rights to the technology marketed under the name Tricide are licensed by the University of Georgia Research Foundation (UGARF) to Molecular Therapeutics, which pays a royalty to UGARF for those rights. A percentage of the royalties is paid to the inventors. Dr. Ritchie is a principle in Molecular Therapeutics. Drs. Weinstein, Moore, Wooley, and Ritchie and UGARF have submitted a patent application for the ophthalmic use of chelating solutions.

The authors thank Drs. Ellen Belknap and Dennis Brooks for providing ophthalmic fungal isolates, Alcon Research Incorporated for donating reference-grade natamycin, and Melinda Pethel for technical assistance.

Cover American Journal of Veterinary Research
American Journal of Veterinary Research
Publication Date:
01 Apr 2006
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