To determine whether intravitreal dexa methasone administration can alter the elimination of intravitreal vancomycin hydrochloride in rabbit eyes with experimental Streptococcus pneumoniae endophthalmitis. Methods: Albino rabbits were infected with an intravitreal inoculum of S pneumoniae (2 ϫ 10 3 colony-forming units) and randomized after 24 hours to treatment with intravitreal vancomycin hydrochloride (1 mg), alone or in combination with intravitreal dexamethasone (400 µg). For comparison, uninfected eyes were similarly treated. All eyes were enucleated 24, 48, or 72 hours after treatment, and vitreous levels of vancomycin were quantitated using a fluorescence polarizing immunoassay. Results: The half-life of intravitreal vancomycin in infected eyes was prolonged from 48 to 84 hours when eyes were treated with dexamethasone. Conversely, such treatment shortened the half-life in uninfected eyes from 56 to 42 hours. Conclusions: Intravitreal dexamethasone administration reduces the elimination of intravitreal vancomycin in rabbit eyes with pneumococcal endophthalmitis, whereas an opposite effect is noted in uninfected eyes.
Most HIV-infected patients with newly diagnosed CMV retinitis had visual symptoms at presentation regardless of the zone of retinal involvement. The incidence of visual symptoms correlated with the degree of retinal involvement.
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. Intraocular fungal infection can result from an exogenous inoculation of the microorganism, as in posttraumatic or postoperative endophthalmitis, or from an endogenous source, as in patients with fungemia. Fungal endophthalmitis accounts for 12% of all cases of infectious endophthalmitis and is a leading cause of endogenous infectious endophthalmitis (29). The most common cause of fungal endophthalmitis is Candida albicans.Traditionally, the commonly used therapy for fungal endophthalmitis consists of intravenous amphotericin B, used alone or in combination with vitrectomy and intravitreal injection of amphotericin B (1, 8, 14-16, 20, 22, 23). Although intravenous amphotericin B therapy is often effective for treatment of chorioretinitis associated with fungal endophthalmitis, treatment failure can occur in eyes with advanced endophthalmitis with marked vitreous infiltrates due to the poor penetration of the drug into the vitreous (8). In addition, systemic administration of the drug requires prolonged hospitalization and is associated with unpleasant and potentially dangerous side effects. Treatment efficacy for advanced endophthalmitis may be enhanced by combining systemic amphotericin B therapy with vitrectomy and intravitreal amphotericin B injections, but such procedures are associated with potential morbidity.For these reasons, the current advocated treatment for fungal endophthalmitis is controversial, and the therapy often is individualized on the basis of the severity of the endophthalmitis (8). In patients with endogenous Candida endophthalmitis without evidence of systemic infection, vitrectomy alone or vitrectomy...
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