TY - JOUR
T1 - Combination Therapy in Experimental Invasive Aspergillosis
AU - Andriole, Vincent T.
AU - George, David
AU - Kordick, Dorsey
AU - Miniter, Peggy
AU - Patterson, Thomas F.
N1 - Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 1993/9
Y1 - 1993/9
N2 - Combination antifungal therapy was assessed in an immunosuppressed rabbit model of invasive aspergillosis. Treatment with fluconazole, amphotericin B, or a combination of both significantly prolonged survival of animals lethally challenged with Aspergillus fumigatus. High-dose amphotericin B was the most effective therapy for invasive aspergillosis. Although no antagonism was seen when fluconazole was given prophylactically or therapeutically in combination with amphotericin B, combination therapy did not augment the antifungal activity of amphotericin B. Animals given a sublethal challenge of A.fumigatus had lower mortality rates when given amphotericin B, fluconazole as treatment or prophylaxis, or various combination therapies. Only animals treated with flucytosine had mortality rates comparable to those of controls. No antagonism was observed with combinations of fluconazole and amphotericin B, flucytosine and amphotericin B, or fluconazole and flucytosine. These observations provide evidence that fluconazole, flucytosine, and amphotericin B used in various combinations are not antagonistic and may provide some insight into the treatment of invasive aspergillosis in humans.
AB - Combination antifungal therapy was assessed in an immunosuppressed rabbit model of invasive aspergillosis. Treatment with fluconazole, amphotericin B, or a combination of both significantly prolonged survival of animals lethally challenged with Aspergillus fumigatus. High-dose amphotericin B was the most effective therapy for invasive aspergillosis. Although no antagonism was seen when fluconazole was given prophylactically or therapeutically in combination with amphotericin B, combination therapy did not augment the antifungal activity of amphotericin B. Animals given a sublethal challenge of A.fumigatus had lower mortality rates when given amphotericin B, fluconazole as treatment or prophylaxis, or various combination therapies. Only animals treated with flucytosine had mortality rates comparable to those of controls. No antagonism was observed with combinations of fluconazole and amphotericin B, flucytosine and amphotericin B, or fluconazole and flucytosine. These observations provide evidence that fluconazole, flucytosine, and amphotericin B used in various combinations are not antagonistic and may provide some insight into the treatment of invasive aspergillosis in humans.
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U2 - 10.1093/infdis/168.3.692
DO - 10.1093/infdis/168.3.692
M3 - Article
C2 - 8354911
AN - SCOPUS:0027225946
VL - 168
SP - 692
EP - 698
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
SN - 0022-1899
IS - 3
ER -