Combinatorial strategies for combating invasive fungal infections.
Invasive fungal infections are an important cause of human mortality and morbidity, particularly for immunocompromised populations. However, there remains a paucity of antifungal drug treatments available to combat these fungal pathogens. Further, antifungal compounds are plagued with problems such as host toxicity, fungistatic activity, and the emergence of drug resistance in pathogen populations. A promising therapeutic strategy to increase drug effectiveness and mitigate the emergence of drug resistance is through the use of combination drug therapy. In this review we describe the current arsenal of antifungals in medicine and elaborate on the benefits of combination therapy to expand our current antifungal drug repertoire. We examine those antifungal combinations that have shown potential against fungal pathogens and discuss strategies being employed to discover novel combination therapeutics, in particular combining antifungal agents with non-antifungal bioactive compounds. The findings summarized in this review highlight the promise of combinatorial strategies in combatting invasive mycoses.
a Michael G. DeGroote Institute for Infectious Disease Research and the Department of Biochemistry and Biomedical Sciences , McMaster University , Hamilton , ON , Canada.
Michaela
M
Spitzer
a Michael G. DeGroote Institute for Infectious Disease Research and the Department of Biochemistry and Biomedical Sciences , McMaster University , Hamilton , ON , Canada.
Nicole
N
Robbins
a Michael G. DeGroote Institute for Infectious Disease Research and the Department of Biochemistry and Biomedical Sciences , McMaster University , Hamilton , ON , Canada.
Gerard D
GD
Wright
D000818:Animals; D000935:Antifungal Agents / Q000009:adverse effects / 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; D003453:Cryptococcosis / Q000188:drug therapy; D003454:Cryptococcus / Q000187:drug effects; D055808:Drug Discovery / Q000379:methods*; D025141:Drug Resistance, Fungal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D000072742:Invasive Fungal Infections / Q000188:drug therapy* / Q000382:microbiology; D009181:Mycoses / Q000382:microbiology
D000935:Antifungal Agents
Aspergillus; Candida; Cryptococcus; antifungal; combination therapy; drug synergy