Voice Prosthesis Coated with Sustained Release Varnish Containing Clotrimazole Shows Long-Term Protection against Candida albicans: An InVitro Study.

Ronit Vogt Sionov,Michael Friedman,Irith Gati,Doron Steinberg,Menachem Gross,David Kirmayer

doi:10.3390/molecules26175395

Ronit Vogt Sionov, Michael Friedman + Show 4 more

Open Access

https://doi.org/10.3390/molecules26175395

Copy DOI

Abstract

Fungal biofilm formation on voice prosthesis (VP) is a major health problem that requires repeated replacement of the prosthesis. Candida albicans is one of the pathogens that frequently inhabits the VP. We proposed that coating VPs with sustained-release varnish (SRV) containing clotrimazole (CTZ) might prevent fungal biofilm formation. The long-term antifungal activities of SRV-CTZ- versus SRV-placebo-coated VPs was tested daily by measuring the inhibition zone of C. albicans seeded on agar plates or by measuring the fungal viability of C. albicans in suspension. The extent of biofilm formation on coated VPs was analyzed by confocal microscopy and scanning electron microscopy. We observed that SRV-CTZ-coated VPs formed a significant bacterial inhibition zone around the VPs and prevented the growth of C. albicans in suspension during the entire testing period of 60 days. Fungal biofilms were formed on placebo-coated VPs, while no significant biofilms were observed on SRV-CTZ-coated VPs. HPLC analysis shows that CTZ is continuously released during the whole test period of 60 days at a concentration above the minimal fungistatic concentration. In conclusion, coating VPs with an SRV-CTZ film is a potential effective method for prevention of fungal infections and biofilm formation on VPs.

Highlights

Voice prostheses (VPs) are indwelling silicone valves that are used for speech rehabilitation in patients with laryngeal malignancies after laryngectomy [1]
We initially analyzed the planktonic growth of C. albicans in the presence of CTZ, and found that the minimum fungistatic concentration was 0.3 μg/mL after a 24 h incubation at 37 ◦C when measuring the optical density (OD) at 595 nm in the microdilution assay (Figure 1A)
Microscopic inspection of the fungi showed that C. albicans treated with 0.03 μg/mL CTZ appeared mainly in yeast form with short hyphal outgrowth, which was in sharp contrast to control fungi that have formed an extended network of long hyphae

Summary

Introduction

Voice prostheses (VPs) are indwelling silicone valves that are used for speech rehabilitation in patients with laryngeal malignancies after laryngectomy [1]. Microbial growth is promoted in the environment of the esophagus where they are exposed to food, saliva, liquids, humidity, and temperature close to 37 ◦C [1]. Candida albicans is the predominant fungal species and Staphylococcus aureus is the most frequent bacterial colonizer found on VPs [2]. C. albicans better colonizes surfaces in CO2-rich environments such as those provided by exhaled breath, and the fungi can penetrate the silicone of the device, eventually rendering it completely unusable [1,2]. Due to fungal and bacterial proclivity for growth in such a favorable environment, the median VP lifespan is reported to range between 60–92 days, depending on the device [3,4]

Methods

Results

Conclusion