The current treatment for
pulmonary aspergillosis,
amphotericin B, is toxic and not always effective. This study was done to evaluate combinations of
amphotericin B with other agents in an animal model of
pulmonary aspergillosis. Sprague-Dawley rats were treated with
cortisone acetate, infected intratracheally with 10(6) spores of Aspergillus fumigatus, and followed daily for survival. Mortality among controls started on day 2, and it was 80% by day seven, whereas
therapy with
amphotericin B resulted in survival of all animals. When given alone,
ketoconazole,
5-fluorocytosine and
rifampin did not improve survival. The combination of
ketoconazole with
amphotericin B resulted in complete antagonism. When animals received a combination of
aerosol amphotericin B prophylaxis two days prior to
infection followed by treatments with SCH39304 or
itraconazole seven days after
infection, survival rates were superior as compared to animals that had received
aerosol prophylaxis only. The combinations of either
5-fluorocytosine or
rifampin with
amphotericin B were not better than
amphotericin B alone. While combinations with
5-fluorocytosine or
rifampin appear not to offer any advantage over
therapy with
amphotericin B alone, additional studies to further evaluate the role of
azoles in combination
therapy are needed.