Combination antifungals: an update.
Invasive fungal infections are an important cause of morbidity and mortality in specific patient populations. There has been an impressive increase in the antifungal armamentarium, yet optimal therapies for many invasive fungal infections remain unknown. Genomic sequencing of a number of pathogenic fungi will pave the way to discovering additional newer targets for antifungal drug design. These new discoveries, plus the existing repertoire of antifungal agents, create the need to effectively model single and combination antifungal agents. Future therapies may also include the use of cell-stress pathway inhibitors in combination with existing antifungal agents. This review focuses on combination antifungal therapy against Cryptococcus neoformans, Candida and Aspergillus species. Combination therapy is only supported by randomized clinical trials for cryptococcal meningitis. We review data from in vitro and animal model studies as well as insights from clinical trials to discuss current thoughts and highlight the gaps in our knowledge surrounding combination antifungal therapy.
Segal
Brahm H
BH
Roswell Park Cancer Institute, Division of Infectious Diseases, Elm & Carlton Streets, Buffalo, NY 14263, USA. brahm.segal@roswellpark.org
Steinbach
William J
WJ
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy*; D001230:Aspergillus / Q000187:drug effects; D002175:Candida / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy*; D003455:Cryptococcus neoformans / Q000187:drug effects*; D004359:Drug Therapy, Combination; D016469:Fungemia / Q000188:drug therapy*; D006801:Humans; D016919:Meningitis, Cryptococcal / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D015398:Signal Transduction / Q000187:drug effects
D000935:Antifungal Agents