The echinocandins.
The changing pattern in fungal infections has driven the need to expand the targets of antifungal activity. The echinocandins are the newest addition to the arsenal against fungal infections. Three echinocandins have been approved by the United States Food and Drug Administration: caspofungin, micafungin, and anidulafungin. These agents have a broad spectrum of activity and are similar to each other with respect to in vitro activity against Candida sp, with micafungin and anidulafungin having similar minimum inhibitory concentrations (MICs) that are generally lower than the MIC of capsofungin. The MICs of the echinocandins are highest against Candida parapsilosis; however, whether this will affect clinical outcomes is unknown. Several case reports have identified clinical failure due to elevated MICs with caspofungin or micafungin against Candida albicans, Candida krusei, and C. parapsilosis. Resistance to the echinocandin class was present in some but not all of the isolates. Empiric therapy with one of the echinocandins for candidemia or invasive candidiasis in patients with neutropenia and those without neutropenia appears to be appropriate when one factors in mortality rate, the increasing frequency of non-albicans Candida infections, and the broad spectrum, safety, and fungicidal effect of the echinocandins. After speciation of the organism, continued therapy with an echinocandin can and should be reevaluated. The echinocandins demonstrate similar in vitro and in vivo activity against Aspergillus sp, but only caspofungin is approved for treatment in patients who are intolerant of or refractory to other therapies. Voriconazole and amphotericin B have demonstrated synergy with the echinocandins. The clinical response to combination therapy has been variable; however, the mortality rate appears to be lower with combination therapy than monotherapy. Large controlled trials are needed to determine the role of combination therapy for invasive aspergillosis. Micafungin and anidulafungin generally have a lower frequency of adverse reactions compared with caspofungin. Phlebitis (3.5-25% of patients) and elevated liver enzyme levels (1-15%) occur more often with caspofungin compared with micafungin and anidulafungin (< 8%). Overall, the three echinocandins are relatively safe and effective agents for the treatment of Candida infections.
Cappelletty
Diane
D
College of Pharmacy, University of Toledo, Toledo, Ohio 43606, USA. Diane.cappelletty@utoledo.edu
Eiselstein-McKitrick
Kasi
K
D000077612:Anidulafungin; D000935:Antifungal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001230:Aspergillus / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D000077336:Caspofungin; D003454:Cryptococcus / Q000187:drug effects; D054714:Echinocandins; D005656:Fungal Proteins / Q000627:therapeutic use*; D006801:Humans; D055666:Lipopeptides; D008074:Lipoproteins / Q000627:therapeutic use; D000077551:Micafungin; D008826:Microbial Sensitivity Tests; D009181:Mycoses / Q000188:drug therapy*; D010456:Peptides, Cyclic / Q000494:pharmacology / Q000627:therapeutic use*
D000935:Antifungal Agents; D054714:Echinocandins; D005656:Fungal Proteins; D055666:Lipopeptides; D008074:Lipoproteins; D010456:Peptides, Cyclic; D000077612:Anidulafungin; C007572:echinocandin B; D000077336:Caspofungin; D000077551:Micafungin