We studied the penetration of three azole compounds, ketoconazole, itraconazole, and fluconazole, into the ocular tissues and fluids of rabbits in the presence and absence of ocular inflammation. Drug concentrations were compared with those found in serum and cerebrospinal fluid. The rank order of penetration into eye tissue was fluconazole > ketoconazole > itraconazole. Fluconazole penetrated freely into both inflamed and uninflamed eyes. The presence of inflammation improved penetration of all three compounds into ocular fluids and tissues. Penetration of these azoles into the anterior chamber of uninflamed eyes and into the cerebrospinal fluid was similar. All three azole compounds reduced the number of yeasts found in the eye in hematogenous Candida albicans endophthalmitis in rabbits when therapy was initiated within 24 h of inoculation. However, only ketoconazole significantly reduced yeast counts in the eye when therapy was postponed for 7 days.The incidence of ocular fungal infections has increased (10, 11, 26) due to a number of factors: increased prevalence of immunosuppression associated with organ transplantation and malignancies; prolonged recovery from complex surgical procedures; and increasing use of antibiotics, immunosuppressive agents, intravenous catheters, and hyperalimentation fluids. Endogenous Candida endophthalmitis (ECE) also occurs in heroin addicts
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