In vitro synergy of eugenol and methyleugenol with fluconazole against clinical Candida isolates

Abstract

The species Candida is a group of opportunistic pathogenic commensals in immunecompromised patients. Treatment of Candida infections is becoming increasingly difficult due to antifungal drug resistance, especially with fluconazole (FLC), which is a commonly used azole. In the present study the in vitro antifungal activity of eugenol (EUG) and methyleugenol (MEUG) alone and in combination against 64 FLC-sensitive and 34 FLC-resistant clinical Candida isolates is highlighted. All the strains were susceptible to both the naturally occurring phenyl propanoids. The nature of the interaction was studied from fractional inhibitory concentration indices (FICIs) for both EUG plus FLC, and MEUG plus FLC combinations calculated from chequerboard microdilution assays. FICI values depicted a high synergism of FLC with both compounds, which was greatest with MEUG. FLC-resistant Candida isolates showed high sensitivity to both compounds. No antagonistic activity was seen in the strains tested in the present study. From these results we suggest that EUG and MEUG have great potential as antifungals, and that FLC can be supplemented with EUG and MEUG to treat FLC-resistant Candida infections.

Study of the antifungal potential of (r)-(+)-citronellal and its association with therapeutic agents used in the treatment of vulvovaginal candidiasis

“…In view of this context, the reality of the current clinical situation of the emerging cases of antimicrobial resistance, the treatment of infections by C. albicans and several other microorganisms has become more difficult, reflecting in a higher frequency of therapeutic failure to the monotherapy (AHMAD et al, 2010).…”

“…In these cases, the research of the interactions of natural and synthetic products on the effectiveness of the conventional antifungal medications seems to us as being quite promising if the combination results in a better activity spectrum and reduced toxicity in comparison to complementary schemes of a single agent (ROLING et al, 2002, AHMAD et al, 2010. This way, it seems that the modification of the antimicrobial activity resulting from the associations, with the expansion of the sensitivity profile of resistant fungal strains shows to be a new strategy in clinical practice, with the potential of being a modifier of the resistance profile (CUENCA-ESTRELLA, 2004, OLIVEIRA et al, 2006, RIBEIRO et al, 2013.…”

Antifungal activity of synthetic antiseptics and natural compounds against Candida dubliniensis before and after in vitro fluconazole exposure

“…Similar to the results for carvacrol, the MIC and MFC values for eugenol were higher in the FS C. dubliniensis group than in the FR C. dubliniensis group. Conflicting results have been reported by Ahmad et al 19 , who noted that FR strains had higher sensitivity to eugenol than the standard or clinical strains did. In addition to its use as an antiseptic agent, eugenol is applied topically to dental cavities, used as a component of dental protectives, and combined with zinc oxide to form zinc oxide eugenol, which has restorative and prosthodontic applications in dentistry 20 .…”

“…Thymol causes protein denaturation and damage to cellular membranes, which results in the leakage of intracellular components 5 . As suggested by Ahmad et al 19 , the antifungal activities of carvacrol, eugenol, and thymol against FR and FS C. dubliniensis highlight the possibility that these compounds could expand the existing class of useful antifungal agents. Thus, these compounds might be used in pharmaceutical products, such as the antiseptic ingredients for mouthwashes.…”

Reversing Antifungal Drug Resistance using Natural Plant Products

“…Inhibition of drug efflux pumps using natural plant products seems to be excellent strategy for overcoming or rather reversing drug resistance in pathogenic fungal species. Natural compounds like thymol and carvacrol can be administered along with conventional antifungal drugs to improve the efficacy and reduce the dose administered as they have a synergistic effect [13,[23][24][25]. Fluconazole is the most prescribed azole for fungal infections specially Candidiasis [26,27].…”