Review Question - QID 100875

Caspofungin is an echinocandin that works by inhibiting 1,3-beta-glucan synthase, an enzyme that helps form the cell wall of fungi.

There are a variety of anti-fungal medications with different mechanisms of action. Echinocandins are a class of anti-fungal that work by inhibiting 1,3-beta-glucan synthase, an enzyme that is part of the pathway of beta-glucan synthesis. Beta-glucan is a an important part of the cell wall of certain medically relevant fungi (e.g. Aspergillus). There are only 3 Echinocandins approved by the FDA, caspofungin, micafungin, and anidulafungin (note that they all end in -fungin).

Mayr et al. review the mechanism of action and use of caspofungin. They note that it has an excellent safety profile and has good activity against a range of Candida species and is useful as an alternative therapy for aspergillus infections. They note that organisms resistant to caspofungin have been documented, but there is no clear pattern of factors contributing to caspofungin resistance.

Steinbach et al. enrolled 196 pediatric and 25 neonatal patients in an epidemiological survey of invasive candidiasis in hospitalized patients. They found that most of the infections had non-albicans Candida species as an etiology, and the most commonly used treatments were fluconazole, caspofungin, and liposomal amphotericin B for neonatal patients. For pediatric patients the most commonly prescribed anti-fungals were fluconazole, liposomal amphotericin B and micafungin. They noted that treatment outcomes for both pediatric and neonatal patients were similar regardless of drug class used.

Illustration A is a diagram of the mechanisms of action of several anti-fungals.
Illustration B is an endoscopy image of a patient with esophageal candidiasis.

Incorrect Answers:
Answer 1: Pore formation in cell membranes is the mechanism of action of Polyenes anti-fungals like amphotericin B and Nystatin.
Answer 2: Inhibition of ergosterol synthesis is the mechanism of action of azole anti-fungals (e.g. ketoconazole).
Answer 3: Inhibition of squalene epoxidase is the mechanism of action of Terbinafine.
Answer 4: Inhibition of pyrimidine synthesis is the mechanism of action of flucytosine.