Liposomal amphotericin B (AmBisome) compared with amphotericin B both followed by oral fluconazole in the treatment of AIDS-associated cryptococcal meningitis.

OBJECTIVE: Amphotericin B deoxycholate initial therapy and fluconazole maintenance therapy is the treatment of choice for AIDS-associated cryptococcal meningitis. However, the administration of amphotericin B is associated with considerable toxicity. A potential strategy for reducing the toxicity and increasing the therapeutic index of amphotericin B is the use of lipid formulations of this drug. DESIGN AND METHODS: HIV-infected patients with cryptococcal meningitis were randomized to treatment with either liposomal amphotericin B (AmBisome) 4 mg/kg daily or standard amphotericin B 0.7 mg/kg daily for 3 weeks, each followed by fluconazole 400 mg daily for 7 weeks. During the first 3 weeks, clinical efficacy was assessed daily. Mycological response was primarily evaluated by cerebrospinal fluid (CSF) cultures at days 7, 14, 21 and 70. RESULTS: Of the 28 evaluable patients, 15 were assigned to receive AmBisome and 13 to receive amphotericin B. Baseline characteristics were comparable. The time to and the rate of clinical response were the same in both arms. AmBisome therapy resulted in a CSF culture conversion within 7 days in six out of 15 patients versus one out of 12 amphotericin B-treated patients (P = 0.09), within 14 days in 10 out of 15 AmBisome patients versus one out of nine amphotericin B patients (P = 0.01), and within 21 days in 11 out of 15 AmBisome patients versus three out of eight amphotericin B patients (P = 0.19). When Kaplan-Meier estimates were used to compare time to CSF culture conversion, AmBisome was more effective (P < 0.05; median time between 7 and 14 days for AmBisome versus > 21 days for amphotericin B). AmBisome was significantly less nephrotoxic. CONCLUSIONS: A 3-week course of 4 mg/kg AmBisome resulted in a significantly earlier CSF culture conversion than 0.7 mg/kg amphotericin B, had equal clinical efficacy and was significantly less nephrotoxic when used for the treatment of primary episodes of AIDS-associated cryptococcal meningitis.

Survival after rhino-orbital-cerebral mucormycosis in an immunocompetent patient.

OBJECTIVE: Rhino-orbital-cerebral mucormycosis is usually associated with a poor prognosis and is almost exclusively seen in immunocompromised patients. We report the third documented case of rhino-orbital-cerebral mucormycosis caused by Apophysomyces elegans (a new genus of the family Mucoraceae first isolated in 1979) in an immunocompetent individual. Orbital exenteration and radical debridement of involved adjacent structures combined with intravenous liposomal amphotericin resulted in patient survival. DESIGN: Interventional case report. METHOD: A 59-year-old immunocompetent white man sustained a high-pressure water jet injury to the right inner canthus while cleaning an air conditioner filter. He later had "orbital cellulitis" develop that did not respond to antibiotics and progressed to orbital infarction. Imaging studies and biopsy results led to a diagnosis of mucormycosis. Tissue culture grew Apophysomyces elegans, a new genus of the family Mucoraceae first isolated in 1979. Orbital exenteration and radical debridement of involved adjacent structures, combined with intravenous liposomal amphotericin, resulted in patient survival. RESULTS: After orbital exenteration and debridement of involved adjacent structures along with intravenous liposomal amphotericin, our patient has remained free from relapse with long-term follow-up. CONCLUSIONS: The agent causing this case of rhino-orbital-cerebral mucormycosis (Apophysomyces elegans) contrasts with the three genera most commonly responsible for mucormycosis (Rhizopus, Mucor, and Absidia) in that infections with this agent tend to occur in warm climates, by means of traumatic inoculation, and in immunocompetent patients. Rhino-orbital-cerebral mucormycosis should be considered in all patients with orbital inflammation associated with multiple cranial nerve palsies and retinal or orbital infarction, regardless of their immunologic status. A team approach to management is recommended for early, appropriate surgery and systemic antifungal agents.