Efficacy of amphotericin B or amphotericin B-intralipid in combination with caspofungin against experimental aspergillosis.
OBJECTIVE
Infections caused by Aspergillus species are increasing in importance, especially among immunocompromised hosts. The objective of this study was to evaluate the efficacy of combination treatment consisting of the polyene amphotericin B (AMB) or amphotericin B-intralipid admixture (AMB-IL) and the echinocandin caspofungin (CAS) in experimental murine systemic aspergillosis. Inhibition of synthesis of a major component of the fungal cell wall and an effect on the cell membrane, by combining echinocandin and a polyene, may result in a synergistic interaction in vitro and in vivo against Aspergillus fumigatus.


METHODS
ICR mice were immunosuppressed by intraperitoneal (ip) administration of cyclophosphamide (CY). Three days post-CY administration the mice were inoculated intravenously (iv) with A. fumigatus conidia. Infection and treatment were evaluated during an observation period of 30 days in terms of mortality (survival rate and mean survival time) and morbidity (quantitative determination of fungal burden, histopathology, and detection of serum galactomannan).


RESULTS
The data showed that combined CAS and AMB or AMB-IL treatment increased the survival of the mice (up to 69.2%) as compared to those treated with each agent alone (44.4, 40.7 and 50%, respectively), and prolonged their mean survival time to 22.5 days. These combinations also resulted in reduction of fungal burden in organs, and decrease in serum galactomannan.


CONCLUSIONS
The successful results obtained in the experimental animal model of this study may possibly open the way to more effective management of aspergillosis in humans.
Sionov
Edward
E
Department of Human Microbiology, Sackler School of Medicine, Tel-Aviv University, Ramat Aviv, Tel-Aviv 69978, Israel.
Mendlovic
Sonia
S
Segal
Esther
E
D000666:Amphotericin B / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy*; D000077336:Caspofungin; D004359:Drug Therapy, Combination; D054714:Echinocandins; D005260:Female; D055666:Lipopeptides; D008172:Lung Diseases, Fungal / Q000188:drug therapy*; D051379:Mice; D008813:Mice, Inbred ICR; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000627:therapeutic use*
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D010456:Peptides, Cyclic; D000666:Amphotericin B; D000077336:Caspofungin