methylamphotericin-b and Candidiasis

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

AME appeared to be as effective as AmB in the treatment of mycoses in humans. AME was much less nephrotoxic than AmB, and was better tolerated in terms of rapid onset and reversible adverse reactions. AME may be more ototoxic than AmB. AME, even as AmB and OAME, may cause neurotoxicity and leukoencephalopathy, particularly when high doses are given for long periods.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Candidiasis; Coccidioidomycosis; Cryptococcosis; Female; Follow-Up Studies; Humans; Male; Middle Aged; Mycoses

After intravenous Candida albicans infection, rats received orinthyl amphotericin methyl ester, amphotericin B, or diluent intravenously. At doses of 0.1 and 0.5 mg/kg, the drugs were equally effective in preventing deaths. However, at doses of 2.0 mg/kg, mortality after treatment with amphotericin B was greater than that after placebo, whereas orinthyl amphotericin methyl ester was fully protective.

Topics: Amphotericin B; Animals; Antifungal Agents; Candidiasis; Rats; Rats, Inbred Strains

Quantitative mycologic techniques were used to evaluate the efficacy of topical amphotericin B methyl ester in two models of yeast infection in rabbit eyes. Doses of 1%, 0.5%, and 0.15% were used in a model of superficial Candida albicans infection. The 1% dose of drug was highly efficacious, abolishing the disease after 2 days of treatment. With doses of 0.5% and 0.15%, decreasing efficacy was observed. Antifungal activity did not deteriorate when 1% prednisolone acetate was administered concomitantly with the 1% dose. In a model of deep stromal infection, the administration of topical 1% amphotericin B methyl ester was highly efficacious when the corneal epithelium was absent. Even in corneas with intact epithelium, a reduced though still significant effect was noted.

Topics: Administration, Topical; Amphotericin B; Animals; Antifungal Agents; Candidiasis; Corneal Diseases; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Drug Therapy, Combination; Prednisolone; Rabbits; Time Factors

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

Amphotericin B methyl ester (AME) has been reported to possess in vitro antifungal activity similar to that of amphotericin B and to have less intrinsic toxicity in mice and dogs. For these reasons AME has been porposed as an alternative to amphotericin B in the therapy of deep mycoses. For comparison of the therapeutic efficacy of the two polyenes in laboratory animals before initiation of studies in humans, groups of mice were infected with Candida albicans, Cryptococcus neoformans, and Blastomyces dermatitidis. Treatment consisted of two or more doses of each drug given by the intravenous route. Concurrently, studies of subacute toxicity were conducted in the same species to permit calculation of therapeutic indices. These studies have shown that AME, as the ascorbate salt, is substantially less efficacious than amphotericin B (in colloidal dispersion with sodium deoxycholate) for treatment of the fungal infections and that amphotericin B had a higher therapeutic ratio for all infections studied than did AME.

Topics: Amphotericin B; Animals; Ascorbic Acid; Blastomyces; Blastomycosis; Candida albicans; Candidiasis; Cryptococcosis; Cryptococcus; Cryptococcus neoformans; Dose-Response Relationship, Drug; Drug Evaluation; Lethal Dose 50; Male; Mice