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Antifungal Synergism: A Proposed Dosage for Corneal Storage Medium

Antifungal Synergism: A Proposed Dosage for Corneal Storage Medium Abstract • Fungal infections from eye bank-preserved corneas have led us to search for antifungal agents that will eliminate yeast and mold in McCarey-Kaufman (MK) medium and concurrently be nontoxic. Amphotericin B, natamycin, nystatin, and clotrimazole were tested in synergistic combinations in vitro against nine yeast and six mold specimens. For average yeast and mold concentrations of 3.4 × 104 and 1.36 × 104 colony-forming units (CFUs)/mL at 5 °C, and 3.36 × 104 and 2.3 × 103 CFUs/mL at 37 °C, respectively, a synergistic combination of all four drugs at one twelfth the minimal fungicidal concentrations proved fungicidal. This synergistic combination did not alter donor human corneal morphology under specular microscopy, nor did it inhibit rabbit corneal endothelial cell division preserved and propagated in antifungal supplemented MK medium. The synergistic drug mixture did prove to be fungicidal when the endothelial cells were challenged with fungal inoculum. References 1. Nelson JD, Mindrup EA, Chung CK, et al: Fungal contamination in organ culture . Arch Ophthalmol 1983;101:280-283.Crossref 2. Gandhi SS, Lamberts DW, Perry HD: Donor to host transmission of disease via corneal transplantation . Surv Ophthalmol 1981;25:306-311.Crossref 3. White JH: Fungal contamination of donor eyes . Br J Ophthalmol 1969;53:30-33.Crossref 4. Beyt BW, Waltman SR: Cryptococcal endophthalmitis after corneal transplantation . N Engl J Med 1978;248:825-826.Crossref 5. Larsen PA, Lindstrom RL, Doughman DJ: Torulopsis glabrata endophthalmitis after keratoplasty with an organ-cultured cornea . Arch Ophthalmol 1978;96:1019-1022.Crossref 6. Driebe WT, Stern GA: Microbial keratitis following corneal transplantation . Cornea 1983; 2:41-45.Crossref 7. Ghosheh R: Polyene antibiotics , in Smolin G, Okumota M (eds): Antimicrobial Agents in Ophthalmology . New York, Masson Publishing USA Inc, 1983, chap 16. 8. deLuise VP: Imidazoles: Mechanism of action and clinical ocular use , in Smolin G, Okumota M (eds): Antimicrobial Agents in Ophthalmology . New York, Masson Publishing USA Inc, 1983, chap 17. 9. Havener WH: Antibiotics , in Ocular Pharmacology . St Louis, CV Mosby Co, 1983, chap 6. 10. Medoff G, Kobayashi GS: Strategies in the treatment of systemic fungal infections . N Engl J Med 1980;302:145-155.Crossref 11. Bell RW, Ritchey JP: Subconjunctival nodules after amphotericin B injection . Arch Ophthalmol 1973;90:402-404.Crossref 12. Cutler JE, Binder PS, Paul TO, et al: Metastatic coccoidioid endophthalmitis . Arch Ophthalmol 1978;96:689-691.Crossref 13. Ellison AC: Intravitreal effects of pimaricin in experimental fungal endophthalmitis . Am J Ophthalmol 1976;81:157-161. 14. Shadomy S, Espinel-Ingroff A: Susceptibility testing with antifungal drugs , in Lennette EH, Balows A, Hausler WJ, et al (eds): Manual of Clinical Microbiology , ed 3. Washington, DC, American Society of Microbiology, 1980, chap 62. 15. Sundar Raj CV, Freeman IL, Church RL, et al: Biochemical characterization of procollagen-collagen synthesized by rabbit corneal endothelial cells in culture . Invest Ophthalmol Vis Sci 1979;18:75-84. 16. Goldman KN, Centifanto Y, Kaufman HE, et al: Prevention of surface bacterial contamination of donor corneas . Arch Ophthalmol 1978; 96:2277-2280.Crossref 17. Deighton FJ, Hall NK, Larsh HW: Merthiolate treatment of pathogenic fungi . J Clin Microbiol 1979;10:144-146. 18. Foster CS, Lass JH, Morgan-Wallace K, et al: Ocular toxicity of topical antifungal agents . Arch Ophthalmol 1981;99:1081-1084.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Ophthalmology American Medical Association

Antifungal Synergism: A Proposed Dosage for Corneal Storage Medium

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Publisher
American Medical Association
Copyright
Copyright © 1985 American Medical Association. All Rights Reserved.
ISSN
0003-9950
eISSN
1538-3687
DOI
10.1001/archopht.1985.01050020102030
Publisher site
See Article on Publisher Site

Abstract

Abstract • Fungal infections from eye bank-preserved corneas have led us to search for antifungal agents that will eliminate yeast and mold in McCarey-Kaufman (MK) medium and concurrently be nontoxic. Amphotericin B, natamycin, nystatin, and clotrimazole were tested in synergistic combinations in vitro against nine yeast and six mold specimens. For average yeast and mold concentrations of 3.4 × 104 and 1.36 × 104 colony-forming units (CFUs)/mL at 5 °C, and 3.36 × 104 and 2.3 × 103 CFUs/mL at 37 °C, respectively, a synergistic combination of all four drugs at one twelfth the minimal fungicidal concentrations proved fungicidal. This synergistic combination did not alter donor human corneal morphology under specular microscopy, nor did it inhibit rabbit corneal endothelial cell division preserved and propagated in antifungal supplemented MK medium. The synergistic drug mixture did prove to be fungicidal when the endothelial cells were challenged with fungal inoculum. References 1. Nelson JD, Mindrup EA, Chung CK, et al: Fungal contamination in organ culture . Arch Ophthalmol 1983;101:280-283.Crossref 2. Gandhi SS, Lamberts DW, Perry HD: Donor to host transmission of disease via corneal transplantation . Surv Ophthalmol 1981;25:306-311.Crossref 3. White JH: Fungal contamination of donor eyes . Br J Ophthalmol 1969;53:30-33.Crossref 4. Beyt BW, Waltman SR: Cryptococcal endophthalmitis after corneal transplantation . N Engl J Med 1978;248:825-826.Crossref 5. Larsen PA, Lindstrom RL, Doughman DJ: Torulopsis glabrata endophthalmitis after keratoplasty with an organ-cultured cornea . Arch Ophthalmol 1978;96:1019-1022.Crossref 6. Driebe WT, Stern GA: Microbial keratitis following corneal transplantation . Cornea 1983; 2:41-45.Crossref 7. Ghosheh R: Polyene antibiotics , in Smolin G, Okumota M (eds): Antimicrobial Agents in Ophthalmology . New York, Masson Publishing USA Inc, 1983, chap 16. 8. deLuise VP: Imidazoles: Mechanism of action and clinical ocular use , in Smolin G, Okumota M (eds): Antimicrobial Agents in Ophthalmology . New York, Masson Publishing USA Inc, 1983, chap 17. 9. Havener WH: Antibiotics , in Ocular Pharmacology . St Louis, CV Mosby Co, 1983, chap 6. 10. Medoff G, Kobayashi GS: Strategies in the treatment of systemic fungal infections . N Engl J Med 1980;302:145-155.Crossref 11. Bell RW, Ritchey JP: Subconjunctival nodules after amphotericin B injection . Arch Ophthalmol 1973;90:402-404.Crossref 12. Cutler JE, Binder PS, Paul TO, et al: Metastatic coccoidioid endophthalmitis . Arch Ophthalmol 1978;96:689-691.Crossref 13. Ellison AC: Intravitreal effects of pimaricin in experimental fungal endophthalmitis . Am J Ophthalmol 1976;81:157-161. 14. Shadomy S, Espinel-Ingroff A: Susceptibility testing with antifungal drugs , in Lennette EH, Balows A, Hausler WJ, et al (eds): Manual of Clinical Microbiology , ed 3. Washington, DC, American Society of Microbiology, 1980, chap 62. 15. Sundar Raj CV, Freeman IL, Church RL, et al: Biochemical characterization of procollagen-collagen synthesized by rabbit corneal endothelial cells in culture . Invest Ophthalmol Vis Sci 1979;18:75-84. 16. Goldman KN, Centifanto Y, Kaufman HE, et al: Prevention of surface bacterial contamination of donor corneas . Arch Ophthalmol 1978; 96:2277-2280.Crossref 17. Deighton FJ, Hall NK, Larsh HW: Merthiolate treatment of pathogenic fungi . J Clin Microbiol 1979;10:144-146. 18. Foster CS, Lass JH, Morgan-Wallace K, et al: Ocular toxicity of topical antifungal agents . Arch Ophthalmol 1981;99:1081-1084.Crossref

Journal

Archives of OphthalmologyAmerican Medical Association

Published: Feb 1, 1985

References