Digestion of Echinocandins.

K. KELLEY, S. CHAPMAN, J. D. CLEARY;

Author address: 

Univ. of Mississippi Med. Ctr., Jackson, MS.

Abstract: 

Backround: Breakthrough, superficial yeast (oral-pharyngeal, OPC) infections have been reported despite prophylactic or treatment with systemic echinocandins. Enzymatic digestion in saliva has been postulated as a cause of these therapeutic failures. Our purpose is to dentify sources of echinocandin "œdigestion" from salival enzymes. Methods: Anidulafungin 10-1000ug/mL was tested alone or in combination with salivary enzymes including; Amylase (0-500 units/mL), carboxypeptidase A (0-100 units/mL) & B (0-100 units/mL), leucine aminopeptidase (0-200 units/mL), invertase (0-200 units/mL), kallikrein (0-10ug/mL), lactoperoxidase (0-60 units/mL), lysozyme (0-200units/mL). Incubation of salivary enzymes or sham with anidulafungin was performed for 48 hours at 27oC. Antifungal concentrations were assessed using bioassay. In brief, overnight Candida albicans cultures were grown in Mueller Hinton broth at 37oC. Approximately 1x106 C. albicans cells were plated on Mueller Hinton agar. Nitrocellulose discs (1mm) were saturated with 15uL of each sample (drug or enzyme/drug mixture), placed on inoculated agar and incubated for 48 hours at 37oC. ANOVA was performed to test for significance. Results: All enzymes "œdigested" anidulafungin, decreasing measured concentrations 8-12%. However, amylase, leucine aminopeptidase, lactoperoxidase significantly decreased measured concentrations nearly (24%) while carboxypeptidase A & B decreased measured concentration 30 & 37%, respectively. Invertase and kallikrein did not significantly affect outcomes. A natural product (Enzymedica) containing a combination of these enzymes decreased anidulafungin nearly 20%. Conclusions: Common salivary enzymes or pharmaceutical replacement enzymes decreased concentrations of anidulafungin, presumably through ring digestion. These data may suggest a mechanism for decreased clinical responsiveness of OPC.
2006

abstract No: 

M-366

Full conference title: 

46th Interscience Conference on Antimicrobial Agents and Chemotherapy
    • ICAAC 46th