Aerosol hamycin is effective for prophylaxis and therapy in a rat model of pulmonary aspergillosis.

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. At 48 h after administrating a single 0.68 or 1.36 mg/kg dose of aero-H, mean lung concentrations were 1.25 and 2.60 mg/g tissue, respectively. From the results of the present study it was concluded that aero-H killed inhaled spores and delays the progression of pulmonary aspergillosis by inhibiting mycelial proliferation.