methylamphotericin-b and Endophthalmitis

To compare in vitro susceptibility of amphotericin B (AMB) and amphotericin B methyl ester (AME) (a more soluble and less toxic formulation of AMB) against Candida albicans isolates recovered from human cases of endophthalmitis.. The in vitro susceptibility of AMB and AME was determined for C. albicans isolates recovered from endophthalmitis (N=10) and for C. albicans ATCC reference strain 90028 using the Clinical and Laboratory Standards Institute M27-A2 (NCCLS/CLSI) broth dilution method. All isolates were obtained from samples of vitreous humor of patients with suspected endophthalmitis within the last 5 years at the Bascom Palmer Eye Institute, University of Miami Miller School of Medicine (Miami, FL).. The minimal inhibitory concentrations (MICs) of AME were equal to or lower than values for AMB in 7 of the 10 isolates; range: AME (0.125-1 μg/mL) versus (0.5-1 μg/mL) for AMB. The MIC(90) value of both drugs was equal (1 μg/mL). Compared with AMB, the minimal fungicidal concentrations (MFCs) of AME were equal to or lower in 8 of 10 isolates; range: AME (0.125-2 μg/mL) versus AMB (0.25-4 μg/mL). MFC(90) values of AME (1 μg/mL) was slightly superior to AMB (2 μg/mL). The MIC of the quality control strain (ATCC(®) 90028) was within an acceptable range.. AME was equivalent to AMB in vitro against C. albicans. This formula may offer a slightly more efficient and less toxic formulation for the treatment of Candida endophthalmitis.

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Candidiasis; Endophthalmitis; Eye Infections, Fungal; Humans; Microbial Sensitivity Tests; Solubility; Vitreous Body

Progressive endogenous Candida albicans endophthalmitis was established in rabbits by intravenous (IV) injection of blastospores (2.0 to 5.0 x 10/kg). Severity of infection was directly related to the strain and inoculum size. Intravenous amphotericin B (1.0 mg/kg/day), IV amphotericin B methyl ester ascorbate (5.0 mg/kg/day), and oral ketoconazole (80 mg/kg/day) effectively prevented or reduced the severity of infection when therapy was initiated 24 hours following inoculation of blastospores and continued for five to seven days. Intravenous miconazole (30 mg/kg/day) was ineffective in this model. Intravenous amphotericin B(1.0 to 2.0 mg/kg on alternate days), IV amphotericin B methyl ester ascorbate (5.0 mg/kg/day), and oral ketoconazole (80 mg/kg/day reduced the severity of C albicans endophthalmitis when therapy was initiated seven days following injection of blastospores and continued for 28 days. Oral flucytosine (75 and 150 mg/kg/day in four doses) produced uniformly fatal hepatic necrosis in uninfected rabbits.

Topics: Amphotericin B; Animals; Antifungal Agents; Candidiasis; Endophthalmitis; Imidazoles; Injections, Intravenous; Ketoconazole; Male; Piperazines; Rabbits

Topics: Amphotericin B; Animals; Antifungal Agents; Candidiasis; Disease Models, Animal; Drug Therapy, Combination; Endophthalmitis; Fluorescein Angiography; Imidazoles; Injections, Intravenous; Ketoconazole; Miconazole; Microbial Sensitivity Tests; Piperazines; Rabbits; Retinitis; Time Factors