Combination antifungal therapy: where are we now, and where are we going?
Combination therapy with amphotericin B and flucytosine is considered to be the treatment of choice for cryptococcal infections. However, for other infections and combinations of antifungal infections, the data are less clear-cut. The concurrent use of amphotericin B with an azole has elicited controversy, given the potential of antimicrobial antagonism. The results of one recent candidemia study suggest that the potential antagonism may not be an issue; the combination of amphotericin B and fluconazole provided more effective clearance of Candida from the bloodstream than did fluconazole used alone. Several in vitro and animal studies have shown antagonism between the azoles and amphotericin B for aspergillosis. However, introduction of the new class of agents that target beta-glucan synthase (echinocandins) has invigorated the prospects of combination therapy. The echinocandins and polyenes are not antagonistic, and there is evidence that the echinocandins may provide additive to synergistic activity in combination with triazoles. For patients whose aspergillosis is progressing despite monotherapy, the addition of a second agent, such as an echinocandin, may be reasonable.
Marr
Kieren
K
Program in Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.
D000666:Amphotericin B / Q000627:therapeutic use*; D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy; D001393:Azoles / Q000627:therapeutic use*; D002177:Candidiasis / Q000188:drug therapy; D000077336:Caspofungin; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D054714:Echinocandins; D015725:Fluconazole / Q000627:therapeutic use; D006801:Humans; D066298:In Vitro Techniques; D055666:Lipopeptides; D008074:Lipoproteins / Q000627:therapeutic use; D000077551:Micafungin; D009181:Mycoses / Q000188:drug therapy*; D010456:Peptides, Cyclic / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use; D065819:Voriconazole
D000935:Antifungal Agents; D001393:Azoles; D054714:Echinocandins; D055666:Lipopeptides; D008074:Lipoproteins; D010456:Peptides, Cyclic; D011743:Pyrimidines; D014230:Triazoles; D000666:Amphotericin B; D015725:Fluconazole; D000077336:Caspofungin; D065819:Voriconazole; D000077551:Micafungin