The overall purpose of this proposal is to develop more effective ocular antifungal therapy through an increased understanding of the efficacy and pharmacokinetics of antifugal agents as they apply to the eye. We plan to continue our therapeutic studies of topical antifungal agents using our quantitative models of Candida keratitis in the rabbit eye. We will investigate the susceptibility of different growth phases of the inoculum to antifungal agents and will develop dose response data for various drugs. The predictive value of in vitro susceptibility tests will be evaluated in this model for a large series of strains and we will investigate the phenomenon of potentiation and antogonism when combinations of antifungal agents are used in vivo. The relationship of the adverse effect of steroid to the efficacy of antifungal agents will be explored with a number of isolates. We plan to continue our studies of drug levels in the eye following topical and periocular administration in order to define the kinetics of uptake and clearance. Newer drugs, particularly liposomally bound antifungal agents will be evaluated in this model.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY001621-10
Application #
3256053
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1979-04-01
Project End
1987-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
10
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37203
Braun, B R; Head, W S; Wang, M X et al. (2000) Identification and characterization of TUP1-regulated genes in Candida albicans. Genetics 156:31-44
Wang, M X; Shen, D J; Liu, J C et al. (2000) Recurrent fungal keratitis and endophthalmitis. Cornea 19:558-60
O'Day, D M; Head, W S (2000) Advances in the management of keratomycosis and Acanthamoeba keratitis. Cornea 19:681-7
O'Day, D M; Head, W S; Csank, C et al. (2000) Differences in virulence between two Candida albicans strains in experimental keratitis. Invest Ophthalmol Vis Sci 41:1116-21
O'Day, D M; Head, W S; Robinson, R D et al. (1999) Contact lens-induced infection--a new model of Candida albicans keratitis. Invest Ophthalmol Vis Sci 40:1607-11
Chang, M S; Tsai, J C; Yang, R et al. (1997) Induction of rabbit cyclooxygenase 2 in the anterior uvea following glaucoma filtration surgery. Curr Eye Res 16:1147-51
Lamps, C A; Oeltmann, T N; Collins Jr, M J et al. (1995) Development of a chitin assay for the quantification of fungus. Curr Eye Res 14:637-41
Klippenstein, K; O'Day, D M; Robinson, R D et al. (1993) The qualitative evaluation of the pharmacokinetics of subconjunctivally injected antifungal agents in rabbits. Cornea 12:512-6
O'Day, D M; Head, W S; Robinson, R D et al. (1992) The evaluation of therapeutic responses in experimental keratomycosis. Curr Eye Res 11:35-44
O'Day, D M; Head, W S; Robinson, R D et al. (1992) Ocular pharmacokinetics of saperconazole in rabbits. A potential agent against keratomycoses. Arch Ophthalmol 110:550-4

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