Antifungal Combinations in Dermatophytes

Abstract

Dermatophytes are the most common cause of fungal infections worldwide, affecting millions of people annually. The emergence of resistance among dermatophytes along with the availability of antifungal susceptibility procedures suitable for testing antifungal agents against this group of fungi make the combinatorial approach particularly interesting to be investigated. Therefore, we reviewed the scientific literature concerning the antifungal combinations against dermatophytes. A literature search on the subject performed in PubMed yielded 68 publications: 37 articles referring to in vitro studies and 31 articles referring to case reports or clinical studies. In vitro studies involved over 400 clinical isolates of dermatophytes (69% Trichophyton spp., 29% Microsporum spp., and 2% Epidermophyton floccosum). Combinations included two antifungal agents or an antifungal agent plus another chemical compound including plant extracts or essential oils, calcineurin inhibitors, peptides, disinfectant agents, and others. In general, drug combinations yielded variable results spanning from synergism to indifference. Antagonism was rarely seen. In over 700 patients with documented dermatophyte infections, an antifungal combination approach could be evaluated. The most frequent combination included a systemic antifungal agent administered orally (i.e., terbinafine, griseofulvin, or azole—mainly itraconazole) plus a topical medication (i.e., azole, terbinafine, ciclopirox, amorolfine) for several weeks. Clinical results indicate that association of antifungal agents is effective, and it might be useful to accelerate the clinical and microbiological healing of a superficial infection. Antifungal combinations in dermatophytes have gained considerable scientific interest over the years and, in consideration of the interesting results available so far, it is desirable to continue the research in this field.

Apiaceae Essential Oils: Boosters of Terbinafine Activity against Dermatophytes and Potent Anti-Inflammatory Effectors

“…It is known that such compounds are lipophilic and have a small molecular size which enable their passive diffusion through fungi membranes [16]. Volatile compounds exert their fungicidal activity through different mechanisms of action that include, among others, the perturbation of the lipid membrane organization [60] followed by the increased permeability of the fungal cell wall/membrane, the extravasation of cell constituents, the inhibition of ergosterol synthesis, and cell lysis [15,23]. Moreover, it was reported that several main constituents of the Apiaceae EOs included in our study acted on the virulence factors and resistance mechanisms of T. rubrum.…”

“…Considering the lipophilic nature of EOs components, their high volatility and chemical instability, the encapsulation in nanoformulated delivery systems could be an approach to overcome such limitations and boost the antidermatophytic activity of EOs [15,22,82]. The additional data regarding their skin and nail permeation, elucidation of their mechanism of activity, and whether in vitro results translate into similar outcomes in in vivo models, are in high demand.…”

“…Combinatorial strategies associating conventional antifungals with plant-derived products represent a promising approach to increase the efficacy of extant treatment regimens in dermatophytosis and to overcome fungal resistance [14,15]. In this context, synergistic combinations can exert a multi-target antifungal activity, thus increasing the potency of conventional drugs and tackling multi-drug microbial resistance.…”

“…The antidermatophytic propensities of EOs are also well-documented and include the disruption of the cell wall/membrane; the inhibition of spore germination, ergosterol and cellular proteins synthesis; efflux pumps, and biofilm formation [23,24]. Moreover, EOs exhibit anti-inflammatory effects, thus supporting lesion healing and alleviating symptoms related to dermatophytosis [14,15]. Apiaceae (Umbelliferae) family comprises 446 genera of 3540 herbaceous species distributed worldwide, many of them used in the food, pharmaceutical, and cosmetic industries [25,26].…”

Honokiol and Magnolol: Insights into Their Antidermatophytic Effects

“…Combination therapy associating antifungal drugs is already used to improve the monotherapy results in clinical settings of refractory dermatophytosis [28,29]. In addition, combinatorial strategies associating conventional drugs (e.g., terbinafine) and plant phenolics have already been proposed as a complementary therapy against dermatophytes [21,30].…”