Alternate-Day Amphotericin B Therapy in the Treatment of Rhinocerebral Phycomycosis (Mucormycosis)

Successful treatment of rhinocerebral phycomycosis is limited because of late diagnosis, resistance of the etiological agents to antifungal drugs, inaccessibility of the lesions, and the fulminant nature of the disease, especially in the patient with diabetic acidosis. Two diabetic patients with rhinocerebral phycomycosis and acidosis were successfully treated by 1 alternate-day amphotericin B administered intravenously at 1.2 mg/kg body weight, 2 control of the diabetic acidosis, 3 local surgical excision of involved sinus tissues, and 4 irrigation of paranasal sinuses with amphotericin B. Mean 48-hr serum levels of amphotericin B were 0.34 µg/ml and 0.45 µg/ml in the two patients. The minimal inhibitory concentration of amphotericin B for Rhizopus oryzae in one patient was 1,000 µg/ml. Although the high blood level of amphotericin B needed to inhibit growth of the organism is unattainable using ordinary doses, the drug is known to be effective in vivo in phycomycete-infected animals and should be part of the therapeutic regimen in human phycomycosis. Creatinine clearance was found to be a more sensitive parameter of renal function than blood urea nitrogen or serum creatinine and was decreased in both patients during treatment with amphotericin B. Ater the drug was discontinued, creatinine clearance returned to normal levels in one patient and to near-pretreatment levels in the second patient. Alternate-day therapy with intravenously administered amphotericin B produced serum levels of the drug 48 hr after infusion that are considered to be adequate for most of the systemic mycotic agents. This regimen was tolerated better by the patients and may have offered less hazard of renal damage during treatment than daily therapy.