Echinocandin antifungal drugs.
The echinocandins are large lipopeptide molecules that are inhibitors of beta-(1,3)-glucan synthesis, an action that damages fungal cell walls. In vitro and in vivo, the echinocandins are rapidly fungicidal against most Candida spp and fungistatic against Aspergillus spp. They are not active at clinically relevant concentrations against Zygomycetes, Cryptococcus neoformans, or Fusarium spp. No drug target is present in mammalian cells. The first of the class to be licensed was caspofungin, for refractory invasive aspergillosis (about 40% response rate) and the second was micafungin. Adverse events are generally mild, including (for caspofungin) local phlebitis, fever, abnormal liver function tests, and mild haemolysis. Poor absorption after oral administration limits use to the intravenous route. Dosing is once daily and drug interactions are few. The echinocandins are widely distributed in the body, and are metabolised by the liver. Results of studies of caspofungin in candidaemia and invasive candidiasis suggest equivalent efficacy to amphotericin B, with substantially fewer toxic effects. Absence of antagonism in combination with other antifungal drugs suggests that combination antifungal therapy could become a general feature of the echinocandins, particularly for invasive aspergillosis.
Denning
David W
DW
Education and Research Centre, Wythenshawe Hospital, Southmoor Road, M23 9LT, Manchester, UK. ddenning@man.ac.uk
D000666:Amphotericin B / Q000627:therapeutic use; D000935:Antifungal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy*; D002177:Candidiasis / Q000188:drug therapy*; D000077336:Caspofungin; D002986:Clinical Trials as Topic; D054714:Echinocandins; D005656:Fungal Proteins; D006801:Humans; D055666:Lipopeptides; D008074:Lipoproteins / Q000627:therapeutic use; D000077551:Micafungin; D010455:Peptides / Q000627:therapeutic use; D010456:Peptides, Cyclic / Q000627:therapeutic use; D016896:Treatment Outcome
D000935:Antifungal Agents; D054714:Echinocandins; D005656:Fungal Proteins; D055666:Lipopeptides; D008074:Lipoproteins; D010455:Peptides; D010456:Peptides, Cyclic; D000666:Amphotericin B; C042101:cilofungin; C007572:echinocandin B; D000077336:Caspofungin; D000077551:Micafungin