Antifungal combination therapy

Abstract

There is described antifungal combination therapy comprising the use of known antifungal agents such as the azoles or polyenes in combination with a pneumocandin derivative antifungal agent. More particularly, the invention relates to antifungal combination therapy comprising the use of azoles such as fluconazole, voriconazole, itraconazole, ketoconazole, miconazole, ER 30346, SCH 56592; polyenes such as amphotericin B, nystatin or liposomal and lipid forms thereof such as Abelcet, AmBisome and Amphocil; purine or pyrimidine nucleotide inhibitors such as flucytosine; or polyoxins such as nikkomycins, in particular nikkomycin Z or other chitin inhibitors, elongation factor inhibitors such as sordarin and analogs thereof, mannan inhibitors such as predamycin, bactericidal/permeability-inducing (BPI) protein products such as XMP.97 or XMP.127 or complex carbohydrate antifungal agents such as CAN-296 in combination with a pneumocandin derivative as described herein.

1. A method of treating fungal infection which comprises administering therapeutically effective amounts of a pneumocandin derivative with a compound selected from an azole, polyene, purine nucleotide inhibitor, pyrimidine nucleotide inhibitor, mannan inhibitor, protein elongation factor inhibitor or bactericidal/permeability increasing protein product. 
     
     
       2. The method of  claim 1  which comprises administering therapeutically effective amounts of a pneumocandin derivative and a polyene. 
     
     
       3. The method of  claim 1  which comprises administering therapeutically effective amounts of a pneumocandin derivative and an azole. 
     
     
       4. The  A method of  claim 1  wherein the pneumocandin derivative is  treating fungal infection which comprises administering therapeutically effective amounts of 
                 
 
       or a pharmaceutically acceptable salt thereof, with a compound selected from an azole, polyene, purine nucleotide inhibitor, pyrimidine nucleotide inhibitor, mannan inhibitor, protein elongation factor inhibitor or bactericidal/permeability increasing protein product. 
     
     
       5. The method of claim  2    4  wherein the pneumocandin derivative is 
                 
 
       or apharmaceutically acceptable salt thereof  compound is a polyene. 
     
     
       6. The method of claim  3    4  wherein the pneumocandin derivative is 
                 
 
       or a pharmaceutically acceptable salt thereof  compound is an azole. 
     
     
       7. The method of claim  1    4  wherein the azole is selected from the group consisting of fluconazole, voriconazole, itraconazole, ketoconazole, miconazole, ER 30346, SCH 56592; the polyenes is selected from the group consisting of amphotericin B, nystatin or liposomal and lipid forms thereof; the purine or pyrimidine nucleotide inhibitors is flucytosine; the polyoxin is nikkomycin Z, the elongation factor inhibitor is sordarin and analogs thereof and the mannan inhibitor is predamycin. 
     
     
       8. The method of  claim 7  wherein the azole is fluconazole. 
     
     
       9. The method of  claim 7  wherein the polyene is amphotericin B. 
     
     
       10. The method of claim  1    4  wherein the infection is caused by a fungal pathogen selected from Cryptococcus spp., Candida spp., Aspeigillus spp., Histoplasma spp., Coccidioides spp., Paracoccidioides spp. Blastomyces spp., Fusarium spp., Sporothrix spp., Trichosporon spp., Rhizopus spp., Pseudallescheria spp. dermatophytes, Paeciliomyces spp., Alternaria spp., Curvularia spp., Exophiala spp., Wangiella spp., Penicillium spp., Saccharomyces spp., Dematiaceous fungi or Pneumnocystis carinii. 
     
     
       11. The method of claim  2    5  wherein the infection is caused by the fungal pathogen selected from Cryptococcus spp., Candida spp., Aspergillus spp., Histoplasma spp., Coccidioides spp., Paracoccidioides spp. Blastomyces spp., Fusarium spp., Sporothrix spp., Trichosporon spp., Rhizopus spp., Pseudallescheria spp., dermatophytes, Paeciliomyces spp., Alternaria spp., Curvularia spp., Exophiala spp., Wangiella spp., Penicillium spp., Saccharomyces spp., Dematiaceous fungi or Pneumocystis carinii. 
     
     
       12. The method of claim  3    6  wherein the infection is caused by the fungal pathogen selected from Cryptococcus spp., Candida spp., Aspergillus spp., Histoplasma spp., Coccidioides spp., Paracoccidioides spp. Blastomyces spp., Fusarium spp., Sporothrix spp., Trichosporon spp., Rhizopus spp., Pseudallescheria spp., dermatophytes, Paeciliomyces spp., Alternaria spp., Curvularia spp., Exophiala spp., Wangiella spp., Penicillium spp., Saccharomyces spp., Dematiaceous fungi or Pneumocystis carinii. 
     
     
       13. The method of  claim 10  wherein the fungal pathogen is selected from Cryptococcus spp., Candida spp. or Aspergillus spp. 
     
     
       14. The method of  claim 11  wherein the fungal pathogen is selected from Cryptococcus spp., Candida spp. or Aspergillus spp. 
     
     
       15. The method of  claim 12  wherein the fungal pathogen is selected from Cryptococcus spp., Candida spp. or Aspergillus spp.