Activity of liposomal nystatin against disseminated Aspergillus fumigatus infection in neutropenic mice.
The purpose of this study was to examine the activity of liposomal nystatin against a disseminated Aspergillus fumigatus infection in neutropenic mice. Mice were made neutropenic with 5-fluorouracil and were administered the antifungal drug intravenously for 5 consecutive days beginning 24 h following infection. Liposomal nystatin, at doses as low as 2 mg/kg of body weight/day, protected neutropenic mice against Aspergillus-induced death in a statistically significant manner at the 50-day time point compared to either the no-treatment, the saline, or the empty-liposome group. This protection was approximately the same as that for free nystatin, a positive control. Histopathological results showed that liposomal nystatin cleared the lungs, spleen, pancreas, kidney, and liver of Aspergillus and that there was no organ damage at the day 5 time point, which was after only three doses of liposomal nystatin. Based on these results in mice, it is probable that liposomal nystatin will be effective against Aspergillus infection in humans.
Wallace
T L
TL
Aronex Pharmaceuticals, Inc., The Woodlands, Texas 77381, USA. twallace@aronex.com
Paetznick
V
V
Cossum
P A
PA
Lopez-Berestein
G
G
Rex
J H
JH
Anaissie
E
E
D000666:Amphotericin B / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001228:Aspergillosis / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000187:drug effects; D004337:Drug Carriers; D008081:Liposomes; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008826:Microbial Sensitivity Tests; D009503:Neutropenia / Q000139:chemically induced / Q000150:complications*; D009761:Nystatin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D009924:Organ Culture Techniques
D000935:Antifungal Agents; D004337:Drug Carriers; D008081:Liposomes; D009761:Nystatin; D000666:Amphotericin B