Hamycin

The efficacy of antifungal agent, hamycin, in a murine model of disseminated candidiasis was studied. Mice were intravenously infected with Candida albicans blastoconidia and treated for 14 days with intraperitoneal hamycin, oral fluconazole, or a combination of these two. Hamycin alone was most efficacious in prolonging survival and in decreasing renal colony counts, usually with complete sterilization of the kidneys by the end of the treatment period. Fluconazole improved survival rates and effected a decrease in renal colony counts, but kidneys were not microbiologically sterilized. Combination therapy with hamycin and fluconazole did not result in a decrease in the efficacy of hamycin by either end point (survival or renal colony counts). High-pressure liquid chromatographic analysis of Hamycin concentrations in serum indicated lowlevels of absorption of the drug. From the results of the present study, it can be concluded that hamycin is effective in the treatment of murine invasive candidiasis and that the theoretical concern about adverse interactions between the two drug does not apply to the dosages studied in these experiments.

Invasive pulmonary aspergillosis is a major life threatening complication among transplant recipient and patients receiving cancer chemotherapy. In a rat model of progressive pulmonary aspergillosis that is characterized by hyphal bronchopneumonia, aerosol hamycin (aero-H; 0.68 mg/kg given 2 days before infection) significantly delayed mortality in rats compared with animals in control group. The first death in the aero-H-treated group occurred on day 12, by which time six of the eight control animals had died. The same dose of aero-H given as treatment (0.68 mg/kg given 24 h after infection and than daily for 6 days) was also effective. In this trial, eight of the ten animals treated with aero-H survived for 7 day, whereas only one of ten control animals survived. Colony counts in lungs homogenates obtained 24 h after infection showed an 80-fold reduction in the number of viable spores in animals that had received 2.8 mg/kg doses of aero-H 2 days prior to infection.

Hamycin, an antifungal agent, has been widely used for tropical applications in fungal infections of human. The present article briefly summarises its clinical studies, progress in the development of liposomal formulations and future research strategy in which both the clinicians and the scientists should be interested.