Antibiofilm Treatment for Onychomycosis and Chronic Fungal Infections

Abstract

Onychomycosis is a difficult-to-treat chronic fungal infection of the nail. The chronic nature of onychomycosis, with relevance to current treatment practices, could be attributed to host anergy, development of increased virulence in causal agents (multidrug resistance efflux pump), and biofilms. Biofilms must be disrupted prior to antifungal treatment suggesting the necessity of combination treatment. Once the biofilm has been disrupted, further techniques in addition to antifungal usage are suggested to ensure a positive prognosis including use of antimicrobial photodynamic therapy or low-frequency surface acoustic waves. Overall, with continued success in developing antibiofilm treatment for bacterial and yeast pathogens, therapy can be more quickly expanded to dermatophytes. With a rise in predisposing factors, it is important to preemptively address treatment for this disease with continued investigation into antibiofilm therapy including optimal treatment combinations and dosages targeted specifically at dermatophytes.

Onychomycosis: An Updated Review

“…The extracellular matrix acts as a protective barrier to the organism such as a fungus within the biofilm [ 167 ]. As such, biofilms increase fungal resistance to antifungal agents by reducing penetration of these agents, along with protection from host defenses [ 81 , 168 ]. Therefore, fungal biofilms may account for the persistence of onychomycosis as well as high rate of recurrence and relapse of onychomycosis [ 167 ].…”

Innovative Physical Approaches for Onychomycosis: Peeling, Lasers and Beyond

“…They include mechanical removal (surgical debridement), chemical disruption of the extracellular polymeric substance components (echinocandins, DNase I enzyme, terpinen-4-ol-loaded lipid nanoparticles, povidone-iodine), thermal disruption (selective photothermolytic effect achieved by laser devices), photochemical damage induced by generation of reactive oxygen species and singlet oxygen using antimicrobial photodynamic therapy, or low-frequency surface acoustic waves. Although the majority of the approaches have shown in vitro and/or in vivo success against bacterial and yeast biofilm disruption, the same may be modulated and fine-tuned to cover dermatophytes [1]. …”

“…Although genetically determined anergy, or lack of immune response to specific fungal antigens, have been reported in patients with chronic dermatophytosis (e.g., ONM is often ignored by the affected patients for years before seeking treatment), factors such as pathogen virulence, drug resistance, and most importantly formation of biofilms by Trichophyton rubrum and Candida spp. contribute to the suboptimal or nonresponse to drugs in ONM [1]. Microbial pathogens including fungi have become smarter and more civilized by secreting a thick layer of extracellular polymeric substance composed of polysaccharides, proteins, lipids, and extracellular DNA, which constitute the biofilm within which they thrive and survive, supporting each other in a colonial fashion.…”

“…In addition to the formation of a robust impenetrable mechanical barrier that insulates their colonies from the environment (especially topical antifungals), biofilms provide increased communication, virulence, better metabolic cooperation, and concerted gene expression, leading to increased resistance to antifungal agents (for example, by activation of drug efflux pump genes). Moreover, the host immune system is unable to access the fungi encased in a mature biofilm, leading to tissue damage from an ineffectual immune response with persistence of infection [1, 2]. Therefore, disruption of fungal biofilms before or concomitant with antifungal drug therapy is essential for successful eradication of infection.…”

Chemical Peeling as an Innovative Treatment Alternative to Oral Antifungals for Onychomycosis in Special Circumstances

“…Apart from being contraindicated or doubtful safety of oral antifungals in such situations, drug interactions that may arise due to patients’ polypharmacy and strong impact of drugs like itraconazole on CYP isoforms constitute major impediments for considering oral antifungal agents in such patients [1]. Topical antifungal medications alone are a poor choice for ONM involving multiple toe nails owing to modest improvement and need for prolonged therapy.…”