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Aims: The in vitro activity of ciclopirox olamine was evaluated against Cryptococcus spp. obtained from the cerebrospinal fluid (CSF) of immunocompromised patients., Methods and Results: The antifungal activity of ciclopirox olamine was tested against Cryptococcus spp. obtained from the CSF of immunocompromised patients, using amphotericin B and fluconazole as controls. The minimal inhibitory concentration was determined following the microdilution method indicated by the Clinical and Laboratory Standards Institute. The minimal fungicide concentration was determined by the absence of growth on Sabouraud dextrose agar. The data obtained showed that antifungal activity of ciclopirox olamine ranged from 0·25 to 1 μg ml(-1) ., Conclusions: This paper underscores the importance of the antifungal potential of ciclopirox olamine against Cryptococcus spp. as an alternative treatment against systemic cryptococosis. In vivo experiments are essential for future medical use., Significance and Impact of the Study: This was the first time that ciclopirox olamine was tested against Cryptococcus spp. using the reference method. The antifungal activity of this drug against this species suggests an applicable potential for systemic cryptococcosis therapy., (© 2010 The Authors. © 2010 The Society for Applied Microbiology.)

The in vivo antifungal activity of the naphthoquinone beta-lapachone against disseminated infection by Cryptococcus neoformans was investigated. Swiss mice were immunosuppressed daily with dexamethasone (0.5 mg per mouse) intraperitoneally for 3 days, the procedure was repeated 4 days later, and the animals were then challenged intravenously with C. neoformans (10(6) CFU/mL) 1 week later. Seven days after infection, the mice were divided into groups and treated daily with beta-lapachone (10 mg/kg, iv) for 7 (N = 6) and 14 days (N = 10). Amphotericin B (0.5 mg/kg) was used as comparator drug and an additional group received PBS. Treatment with beta-lapachone cleared the yeast from the spleen and liver, and the fungal burden decreased approximately 10(4) times in the lungs and brain 14 days after infection when compared to the PBS group (P < 0.05). This result was similar to that of the amphotericin B-treated group. Protection was suggestively due to in vivo antifungal activity of this drug and apparently not influenced by activation of the immune response, due to similar leukocyte cell counts among all groups. This study highlights the prospective use of beta-lapachone for treatment of disseminated cryptococcosis.

7 of 8 dogs receiving combination drug therapy consisting of flucytosine together with amphotericin B and/or a triazole for cryptococcosis or aspergillosis developed cutaneous or mucocutaneous eruptions during the course of treatment. Lesions resolved in all cases following discontinuation of flucytosine despite continued administration of other antifungals, suggesting the eruption was referable primarily to the flucytosine component of therapy. Lesions developed 13 to 41 days (median 20 days) after commencing flucytosine (105 to 188 mg/kg/day divided and given every 8 h; median dose rate 150 mg/kg/day). The cumulative dose of flucytosine given prior to the first signs of the drug eruption ranged from 1.7 to 6.8 g/kg (median 2.3 g/kg). The eruptions consisted of depigmentation, followed by ulceration, exudation and crust formation. The scrotum was affected in all 4 male dogs, the nasal plane in 6 of 7 cases, while the lips, vulva, external ear canal and integument were involved in a smaller number of cases. There was considerable variation in the severity of lesions, with changes being most marked when flucytosine was continued for several days after lesions first appeared. Some dogs experienced malaise and inappetence in association with the suspected drug eruption. Healing took a variable period, typically in excess of 2 weeks after discontinuing flucytosine, with up to 2 months being required for total resolution of the lesions. All lesions resolved eventually without scarring or permanent loss of pigment.