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Cerebral phaeohyphomycosis caused by Ramichloridium mackenziei is universally fatal. All reported cases with long-term follow-up have indicated 100% mortality despite antifungal therapy and surgical intervention. We describe the case of a 62-year-old patient who underwent renal transplantation and had a cerebral abscess caused by R. mackenziei. The infection progressed despite surgical evacuation and therapy with liposomal amphotericin B, itraconazole, and 5-flucytosine. The patient was subsequently treated with the investigational triazole posaconazole oral suspension, 800 mg/day, in divided doses. Treatment with posaconazole resulted in progressive clinical and radiologic improvement. The patient is alive four years after diagnosis and maintained on posaconazole therapy. This case supports the potential role of this extended-spectrum azole in the treatment of this serious fungal infection of the central nervous system.

Ramichloridium obovoideum ("Ramichloridium makenziei") is a rare cause of lethal cerebral phaeohyphomycosis. It has been, so far, geographically restricted to the Middle East. BALB/c mice were inoculated with two strains of R. obovoideum intracranially. Therapy with amphotericin B, itraconazole, or the investigational triazole SCH 56592 was conducted for 10 days. Half the mice were monitored for survival and half were killed for determination of the fungal load in brain tissue. Recipients of SCH 56592 had significantly prolonged survival and lower brain fungal burden, and this result was found for mice infected with both of the fungal strains tested. Itraconazole reduced the brain fungal load in mice infected with one strain but not the other, while amphotericin B had no effect on brain fungal concentrations. This study indicates a possible role of SCH 56592 in the treatment of the serious cerebral phaeohyphomycosis due to R. obovoideum.

Current therapy for leishmaniasis is unsatisfactory. Efficacious and safe oral therapy would be ideal. We examined the efficacy of SCH 56592, an investigational triazole antifungal agent, against cutaneous infection with Leishmania amazonensis and visceral infection with Leishmania donovani in BALB/c mice. Mice were infected in the ear pinna and tail with L. amazonensis promastigotes and were treated with oral SCH 56592 or intraperitoneal amphotericin B for 21 days. At doses of 60 and 30 mg/kg/day, SCH 56592 was highly efficacious in treating cutaneous disease, and at a dose of 60 mg/kg/day, it was superior to amphotericin B at a dose of 1 mg/kg/day. The means of tail lesion sizes were 0.32 +/- 0.12, 0.11 +/- 0.06, 0.17 +/- 0.07, and 0.19 +/- 0.08 mm for controls, SCH 56592 at 60 and 30 mg/kg/day, and amphotericin B recipients, respectively (P = 0.0003, 0.005, and 0.01, respectively). Parasite burden in draining lymph nodes confirmed these efficacy findings. In visceral leishmaniasis due to L. donovani infection, mice treated with SCH 56592 showed a 0.5- to 1-log-unit reduction in parasite burdens in the liver and the spleen compared to untreated mice. Amphotericin B at 1 mg/kg/day was superior to SCH 56592 in the treatment of visceral infection, with a 2-log-unit reduction in parasite burdens in both the liver and spleen. These studies indicate very good activity of SCH 56592 against cutaneous leishmaniasis due to L. amazonensis infection and, to a lesser degree, against visceral leishmaniasis due to L. donovani infection in susceptible BALB/c mice.