Aerosol amphotericin B is effective for prophylaxis and therapy in a rat model of pulmonary aspergillosis.
Invasive pulmonary aspergillosis is a major life-threatening complication among transplant recipients and patients receiving cancer chemotherapy. In a rat model of progressive pulmonary aspergillosis that is characterized by hyphal bronchopneumonia, aerosol amphotericin B (aero-AmB; 1.6 mg/kg given 2 days before infection) significantly delayed mortality in rats compared with animals in a control group. The first death in the aero-AmB-treated group occurred on day 11, by which time seven of the eight control animals had died. The same dose of aero-AmB given as treatment (1.6 mg/kg given 24 h after infection and then daily for 6 days) was also effective. In this trial, eight of the ten animals treated with aero-AmB survived for 7 days, whereas only one of ten control animals survived. Colony counts in lung homogenates obtained 24 h after infection showed an 80-fold reduction in the number of viable spores in animals that had received 6.4-mg/kg doses of aero-AmB 2 days prior to infection. At 48 h after administering a single 1.6- or 3.2-mg/kg dose of aero-AmB, mean lung concentrations were 2.79 and 5.22 micrograms/g of tissue, respectively. We conclude, therefore, that aero-AmB kills inhaled spores and delays the progression of pulmonary aspergillosis by inhibiting mycelial proliferation.
Schmitt
H J
HJ
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Bernard
E M
EM
Häuser
M
M
Armstrong
D
D
D000336:Aerosols; D000666:Amphotericin B / Q000008:administration & dosage* / Q000032:analysis / Q000627:therapeutic use; D000818:Animals; D001228:Aspergillosis / Q000188:drug therapy* / Q000401:mortality / Q000517:prevention & control; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D007274:Injections, Intraperitoneal; D008168:Lung / Q000032:analysis / Q000382:microbiology; D008172:Lung Diseases, Fungal / Q000188:drug therapy* / Q000401:mortality / Q000517:prevention & control; D008297:Male; D009929:Organ Size; D051381:Rats; D011919:Rats, Inbred Strains
D000336:Aerosols; D000666:Amphotericin B