TY - JOUR
T1 - Treatment of exogenous Candida endophthalmitis in rabbits with oral fluconazole
AU - Park, Susanna Soon Chun
AU - D'Amico, D. J.
AU - Paton, B.
AU - Baker, A. S.
PY - 1995
Y1 - 1995
N2 - We investigated the efficacy of oral fluconazole, alone or in combination with oral flucytosine (5FC), in treating Candida endophthalmitis using a rabbit model. Albino rabbits were infected with an intravitreal inoculation of 1,000 CFU of susceptible Candida albicans and randomized 5 days later to receive treatment with oral fluconazole alone (80 mg/kg of body weight per day), a combination of fluconazole and 5FC (100 mg/kg/12 h), or no treatment. The treatment effect was assessed at 2 and 4 weeks after therapy by funduscopy, quantitative vitreous culture, and histopathology. Intravitreal levels of fluconazole, 2 to 24 h after the first dose, were measured to be >10 times the MIC of the drug for C. albicans. Among rabbits treated with fluconazole for 2 weeks, 67% had a >90% reduction in fungal load (P <0.05) and 33% were sterile. After 4 weeks, all had a >99% reduction in fungal load (P <0.05) and 75% were sterile (P = 0.01). This treatment effect was unchanged 4 weeks after discontinuation of fluconazole. Among rabbits treated with fluconazole and 5FC for 2 weeks, 67% died during therapy. Among the surviving rabbits, 75% had a >90% reduction in fungal load (P <0.05) and 25% were sterile. We conclude that oral fluconazole may be useful for treatment of Candida endophthalmitis. Addition of 5FC was associated with high toxicity and minimal additional antifungal effect in our rabbit model.
AB - We investigated the efficacy of oral fluconazole, alone or in combination with oral flucytosine (5FC), in treating Candida endophthalmitis using a rabbit model. Albino rabbits were infected with an intravitreal inoculation of 1,000 CFU of susceptible Candida albicans and randomized 5 days later to receive treatment with oral fluconazole alone (80 mg/kg of body weight per day), a combination of fluconazole and 5FC (100 mg/kg/12 h), or no treatment. The treatment effect was assessed at 2 and 4 weeks after therapy by funduscopy, quantitative vitreous culture, and histopathology. Intravitreal levels of fluconazole, 2 to 24 h after the first dose, were measured to be >10 times the MIC of the drug for C. albicans. Among rabbits treated with fluconazole for 2 weeks, 67% had a >90% reduction in fungal load (P <0.05) and 33% were sterile. After 4 weeks, all had a >99% reduction in fungal load (P <0.05) and 75% were sterile (P = 0.01). This treatment effect was unchanged 4 weeks after discontinuation of fluconazole. Among rabbits treated with fluconazole and 5FC for 2 weeks, 67% died during therapy. Among the surviving rabbits, 75% had a >90% reduction in fungal load (P <0.05) and 25% were sterile. We conclude that oral fluconazole may be useful for treatment of Candida endophthalmitis. Addition of 5FC was associated with high toxicity and minimal additional antifungal effect in our rabbit model.
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M3 - Article
C2 - 7786003
AN - SCOPUS:0028903794
VL - 39
SP - 958
EP - 963
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
SN - 0066-4804
IS - 4
ER -