Oral mucositis caused by Candida glabrata biofilms: failure of the concomitant use of fluconazole and ascorbic acid.

Abstract

Candida glabrata is becoming one of the most prevalent pathogenic yeasts in cases of oral diseases. Mucositis is an recurrent oral infection in immunocompromised patients, and the actual guidelines recommend the use of fluconazole (Flu) for many cases. However, the azole resistance by C. glabrata is renowned, causing a reduced therapeutic response, especially when it occurs in biofilms. In this study, we performed an in vitro evaluation of an alternative pharmacotherapy for C. glabrata biofilm infections, combining ascorbic acid (AA) with Flu. AA is recognized for degrading β-glucans, an important compound of the biofilm matrices, which prevent drug diffusion. Routine clinical 30 or 40 mg/l doses of Flu were applied to C. glabrata biofilms simultaneously with 200 or 300 mg/l of AA. The results showed that this combination effectively promoted the degradation of the biofilm network, but unfortunately, also stimulated the growth of the yeasts population due to release of several glucose monomers during β-glucans hydrolysis. AA lead to the hydrolysis of the β-glucans of the matrix, liberating glucose molecules which are used as carbon souce by the yeasts, thus suppressing the desired antifungal effect of the drug combination with Flu. Unlike to what happens in treatment of bacterial infection, AA should not be used together with Flu in the treating oral mucositis caused by Candida.