Combination of Farnesol with Common Antifungal Drugs: Inhibitory Effect against Candida Species Isolated from Women with RVVC

Abstract

Background and Objectives: Vulvovaginal candidiasis (VVC) is a mucous membrane infection, with an increased rate of antifungal resistance of Candida species. In this study, the in vitro efficacy of farnesol alone or in combination with traditional antifungals was assessed against resistant Candida strains recovered from women with VVC. Materials and Methods: Eighty Candida isolates were identified by multiplex polymerase chain reaction (PCR), and the antifungal susceptibility to amphotericin B (AMB), fluconazole (FLU), itraconazole (ITZ), voriconazole (VOR), clotrimazole (CTZ), and farnesol was tested by the standard microdilution method. The combinations of farnesol with each antifungal were calculated based on the fractional inhibitory concentration index (FICI). Result: Candida glabrata was the predominant species (48.75%) isolated from vaginal discharges, followed by C. albicans (43.75%), C. parapsilosis (3.75%), a mixed infection of C. albicans and C. glabrata (2.5%) and C. albicans and C. parapsilosis (1%). C. albicans and C. glabrata isolates had lower susceptibility to FLU (31.4% and 23.0%, respectively) and CTZ (37.1% and 33.3%, respectively). Importantly, there was “synergism” between farnesol–FLU and farnesol–ITZ against C. albicans and C. parapsilosis (FICI = 0.5 and 0.35, respectively), reverting the original azole-resistant profile. Conclusion: These findings indicate that farnesol can revert the resistance profile of azole by enhancing the activity of FLU and ITZ in resistant Candida isolates, which is a clinically promising result.

A Combination of β-Aescin and Newly Synthesized Alkylamidobetaines as Modern Components Eradicating the Biofilms of Multidrug-Resistant Clinical Strains of Candida glabrata

“…Moreover, some C. glabrata strains are characterized by intrinsic resistance to this antifungal agent [ 12 , 36 ]. Even though azoles are the drugs of first choice in treating candidiasis, pathogens’ susceptibility has decreased dramatically in the last few decades, according to the development of various resistance mechanisms [ 36 , 37 ]. Therefore, the current stock of drugs used to combat fungal infections remains inadequate, and infections caused by C. glabrata strains resistant to a single drug and multiple drugs are becoming a common and difficult therapeutic challenge.…”

“…Searching for new efficient antifungal agents with minimal adverse effects and low toxicity often leads to abundant resources of natural substances, which are mainly present in plants [ 18 , 37 , 39 ] and bee products [ 40 ]. Compounds from natural products not only exhibit antifungal activity but also enhance the effects of synthetic drugs.…”

Molecular association of Candida albicans and vulvovaginal candidiasis: focusing on a solution

“…The inhibition is achieved by negatively regulating the RAS1-cAMP-PKA pathway by targeting CYR1. Farnesol has recently become a prospective drug due to its antifungal efficacy (Nikoomanesh et al, 2023). Probiotic vaginal colonization, particularly with Lactobacillus sp., has also been widely studied and shown to have a significantly lower risk of VVC and to even treat VVC.…”

Farnesol as an antifungal agent: comparisons among MTLa and MTLα haploid and diploid Candida albicans and Saccharomyces cerevisiae

“…For instance, Brasch et al (2014) detailed their effectiveness versus dermatophytes while Katragkou et al (2015) showed their synergistic effectiveness with fluconazole, amphotericin B, and micafungin versus C. albicans biofilms. More recently, Nagy et al (2020) reported that farnesol inhibited growth and biofilm forming ability by C. auris, Dekkerova et al (2022) confirmed a synergistic effect between farnesol and fluconazole in C. auris, and Nikoomanesh et al (2023) confirmed a synergism between farnesol and either fluconazole or itraconazole which restored the original sensitivity of azole-resistant C. albicans and Candida parapsilosis. The idea that C. albicans secretes antifungal molecules as a mechanism of competition with other fungi is longstanding.…”