Newer combination antifungal therapies for invasive aspergillosis.
Optimal therapy for invasive aspergillosis is unknown, and many clinicians have attempted to utilize a combination antifungal approach to improve outcomes. However, while numerous in vitro studies, animal models, and clinical reports suggest the possibility that combination antifungal therapy might offer improved results, there is no definitive accepted strategy. The currently available antifungals used in various combination approaches have not demonstrated clear improvement over monotherapy. The current classes of drugs targeting the cell wall and cell membrane may need adjunctive agents focused on separate cellular pathways, such as cell stress response or cellular signaling, to maximize efficacy. The calcineurin and the Hsp90 pathways are two such untouched arenas in which targeted manipulation may lead to great advances against aspergillosis.
Steinbach
William J
WJ
Department of Pediatrics, Division of Pediatric Infectious Diseases, Duke University, Durham, NC 27710, USA. stein022@mc.duke.edu
Juvvadi
Praveen R
PR
Fortwendel
Jarrod R
JR
Rogg
Luise E
LE
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy* / Q000382:microbiology; D001230:Aspergillus / Q000187:drug effects* / Q000472:pathogenicity; D019703:Calcineurin / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D018841:HSP90 Heat-Shock Proteins / Q000187:drug effects / Q000502:physiology; D006801:Humans
D000935:Antifungal Agents; D018841:HSP90 Heat-Shock Proteins; D019703:Calcineurin