COMPOSITIONS AND METHODS FOR INHIBITING FUNGAL INFECTIONS
Compositions and methods for inhibiting fungal growth by administering AR-12 to a host infected with a fungus such as Histoplasma capsulatum, Aspergillus fumigatus, and Trichophyton rubrum, Paecilomyces, Rhizopus, Fusarium, Scedosporium, Lomentospora, Apophysomyces, Coccidioides, Blastomyces, non-albicans Candida, and Pneumocytis are provided.
1 . A method of inhibiting fungal growth in a host infected with a fungus selected from the group consisting of Histoplasma capsulatum, Aspergillus fumigatus, and Trichophyton rubrum, comprising administering AR-12 to the host in an amount sufficient to reduce fungal growth in the host by about 90%.
2 . The method of claim 1 , wherein the fungal growth is reduced by about 50%.
3 . The method of claim 2 , wherein AR-12 is provided to the host in an amount sufficient to achieve a blood, tissue, or organ concentration between about 10 μM and 40 μM.
4 . The method of claim 2 , wherein AR-12 is provided to the host in an amount sufficient to achieve a blood, tissue or organ concentration between about 8 μM and 24 μM.
5 . A method of inhibiting fungal growth in a host infected with a fungus, comprising administering AR-12 to the host in an amount sufficient to achieve a blood, tissue or organ concentration between about 3 μM and 8 μM, and wherein fungal growth is inhibited between about 10% and 50%.
6 . A method of inhibiting fungal growth in a host infected with one or more fungi selected from the group consisting of Paecilomyces, Rhizopus, Fusarium, Scedosporium, Lomentospora, Apophysomyces, Coccidioides, Blastomyces, non-albicans Candida, and Pneumocytis, comprising administering AR-12 to the host in an amount sufficient to achieve a concentration in the host sufficient to inhibit fungal growth by about 100%.
7 . The method of claim 6 , wherein the fungal growth is reduced by about 50%.
8 . The method of claim 6 , wherein AR-12 is administered in an amount sufficient to achieve a concentration in the blood of the host between about 1 μg/ml to about 100 μg/ml, or an equivalent concentration in tissue or an organ.
9 . The method of claim 7 , wherein AR-12 is administered in amount sufficient to achieve a concentration in the blood of the host between about 1 μg/ml to about 16 μg/ml, or an equivalent concentration in tissue or an organ.
10 . The method of claim 7 , further comprising administering one or more additional compounds to the host, said one or more additional compounds selected from the group consisting of clotrimazole, econazole, ketoconazole, miconazole, tioconazole, fluconazole, posaconazole, itraconazole, voriconazole, isavuconazonium, terbinafine, nystatin, amorolfine, griseofulvin, caspofungin, micafungin, anidulafungin, tevaborole, efinaconazole, amphotericin B deoxycholate, and liposomal amphotericin B.
11 . A method of inhibiting fungal growth in a host infected with a fungus, comprising:
administering AR-12 to the host in an amount sufficient to achieve a concentration in the blood of the host between about 1 μg/ml to about 100 μg/ml, or an equivalent concentration in tissue or an organ, for at least about 24 hours.
12 . The method of claim 11 , wherein AR-12 is administered for at least about 48 hours.
13 . The method of claim 12 , wherein AR-12 is administered for at least 72 hours.
14 . A method of inhibiting fungal growth in a host infected with Pneumocytis comprising administering AR-12 to the host in an amount sufficient to achieve a concentration in the host to reduce fungal growth in the host by about 50%.
15 . The method of claim 14 , wherein AR-12 is administered to the host in an amount sufficient to achieve a concentration in the blood of about 4.82 μg/ml, or an equivalent concentration in a tissue or organ.
16 . The method of claim 15 , wherein the Pneumocytis is Pneumocytis carinii.
17 . The method of claim 14 , wherein AR-12 is administered to the host in an amount sufficient to achieve a concentration in the blood of about 1.78 μg/ml, or an equivalent concentration in a tissue or organ.
18 . The method of claim 17 , wherein the Pneumocytis is Pneumocytis marina.
19 . The method of claim 11 , further comprising administering one or more additional compounds to the host, said one or more additional compounds selected from the group consisting of clotrimazole, econazole, ketoconazole, miconazole, tioconazole, fluconazole, posaconazole, itraconazole, voriconazole, isavuconazonium, terbinafine, nystatin, amorolfine, griseofulvin, caspofungin, micafungin, anidulafungin, tevaborole, efinaconazole, amphotericin B deoxycholate, and liposomal amphotericin B.
20 . A method of inhibiting fungal growth in a host infected with a non-albicans Candida fungus, comprising administering AR-12 to the host in an amount sufficient to achieve a concentration in the host to inhibit non-albicans Candida fungal growth by about 100%.
21 . The method of claim 20 , wherein the fungal growth is reduced by about 50%.
22 . The method of claim 20 , wherein AR-12 is administered in an amount sufficient to achieve a concentration in the host blood between about 1 μg/ml to about 100 μg/ml, or an equivalent concentration in a tissue or organ.
23 . The method of claim 22 , wherein AR-12 is administered in amount sufficient to achieve a concentration in the host blood between about 1 μg/ml to about 16 μg/ml, or an equivalent concentration in a tissue or organ.