Search

Recently, a large number of nosocomial infections have been caused by an emerging pathogen that is rising as a worldwide issue in human health: Candida auris. This yeast is considered resistant to antifungals of the first-line therapies, and consequently it is related to morbidity and mortality. Therefore, the aim of this research was to determine the in vitro anti-C. auris activity against twenty-three resistant clinical strains of different essential oils (EOs), pure or in combination with traditional antifungal agents, mainly caspofungin, fluconazole, micafungin and 5-flucytosine. Broth dilution assay was performed to evaluate the fungistatic and fungicidal effectiveness of fifteen EOs towards all the C. auris isolates. The data demonstrated that EOs were able to prevent C. auris growth, with MIC values ranging from 0.03 to 1% for the efficacious EOs (thyme, cinnamon, geranium, clove bud, lemongrass and mentha of Pancalieri), whereas the MICs were >1% for the ineffective ones. Thereafter, the six most effective EOs were used to perform the checkerboard experiments by assaying simultaneously the activity of EOs and traditional antifungals towards two selected strains. The most promising synergic combinations towards C. auris, depending on the isolate, were those with micafungin and geranium, thyme, cinnamon, lemongrass or clove bud EOs, with fluconazole and mentha of Pancalieri EO, and with 5-flucytosine and mentha of Pancalieri EO. These EOs and their combinations with antifungal drugs may provide a useful therapeutic alternative that could reduce the dose of the individual components, limiting the overall side effects. These associations might be a prospective option for the future treatment of infections, thus helping to overcome the challenging issue of resistance in C. auris.

With respect to other fields, bone tissue engineering has significantly expanded in recent years, leading not only to relevant advances in biomedical applications but also to innovative perspectives. Polycaprolactone (PCL), produced in the beginning of the 1930s, is a biocompatible and biodegradable polymer. Due to its mechanical and physicochemical features, as well as being easily shapeable, PCL-based constructs can be produced with different shapes and degradation kinetics. Moreover, due to various development processes, PCL can be made as 3D scaffolds or fibres for bone tissue regeneration applications. This outstanding biopolymer is versatile because it can be modified by adding agents with antimicrobial properties, not only antibiotics/antifungals, but also metal ions or natural compounds. In addition, to ameliorate its osteoproliferative features, it can be blended with calcium phosphates. This review is an overview of the current state of our recent investigation into PCL modifications designed to impair microbial adhesive capability and, in parallel, to allow eukaryotic cell viability and integration, in comparison with previous reviews and excellent research papers. Our recent results demonstrated that the developed 3D constructs had a high interconnected porosity, and the addition of biphasic calcium phosphate improved human cell attachment and proliferation. The incorporation of alternative antimicrobials—for instance, silver and essential oils—at tuneable concentrations counteracted microbial growth and biofilm formation, without affecting eukaryotic cells’ viability. Notably, this challenging research area needs the multidisciplinary work of material scientists, biologists, and orthopaedic surgeons to determine the most suitable modifications on biomaterials to design favourable 3D scaffolds based on PCL for the targeted healing of damaged bone tissue.

Background: Treatment options for aspergillosis include amphotericin B (AMB) and azole compounds, such as itraconazole (ITZ). However, serious side effects related to these antifungal agents are increasingly evident, and resistance continues to increase. Currently, a new trend in drug discovery to overcome this problem is represented by natural products from plants, or their extracts. Particularly, there is a great interest in essential oils (EOs) recognized for their antimicrobial role towards bacteria, fungi and viruses. Methods: In this study, we evaluated the antifungal activity of eleven commercial EOs—clove, eucalyptus, geranium, hybrid lavender, lavender, lemon, lemongrass, neroli, oregano, tea tree and red red thyme—in comparison with AMB and ITZ against Aspergillus flavus, A. fumigatus and A. niger clinical isolates. Antifungal activity was determined by broth microdilution method, agar diffusion technique, fungistatic and fungicidal activities and vapor contact assay. Results: Gas chromatography–mass spectrometry analysis displayed two groups of distinct biosynthetical origin: monoterpenes dominated the chemical composition of the most oils. Only two aromatic compounds (eugenol 78.91% and eugenyl acetate 11.64%) have been identified as major components in clove EO. Lemongrass EO exhibits the strongest antimicrobial activity with a minimum inhibitory concentration of 0.56 mg/mL and a minimum fungicidal concentration of 2.25–4.5 mg/mL against Aspergillus spp. strains. Clove and geranium EOs were fairly effective in inhibiting Aspergillus spp. growth. Conclusions: These results demonstrate the antimicrobial potential of some EOs and support the research of new alternatives or complementary therapies based on EOs.

The use of essential oils is increasingly being investigated among new therapeutic approaches based on medicinal plants and their extracts. With the wide use of synthetic and semi-synthetic antimicrobial drugs, the spread of drug-resistant clinical isolates has increased, and research is directed towards natural products, such as essential oils, as useful antimicrobial resources. In the context of a prospective infection, we compared the impact of essential oils and common antimicrobial agents on the microbicidal activity of human phagocytes. Here, we present the results of our decades-long investigation into the effectiveness of thyme red oil (26.52% thymol chemotype), tea tree oil (TTO), and Mentha of Pancalieri [(Mentha x piperita (Huds) var. officinalis (Sole), form rubescens (Camus) (Lamiaceae)] essential oils on human polymorphonuclear leukocytes (PMNs) capacity to kill clinical strains of Candida albicans and C. krusei when compared to three antifungal drugs used to treat candidiasis (fluconazole, anidulafungin, and caspofungin) These essential oils demonstrate antifungal drug-like and/or superior efficacy in enhancing intracellular killing by PMNs, even at subinhibitory concentrations. Our results are compared with data in the literature on essential oils and immune system interactions. This comparison would aid in identifying therapeutic solutions to the increasingly prevalent antibiotic resistance as well as filling in any remaining knowledge gaps on the bioactivity of essential oils.

Abstract Background Cryptococcal infections, besides being a problem for immunocompromised patients, are occasionally being a problem for immunocompetent patients. In addition, the lower susceptibility of this yeast to azoles is a growing problem in health care. To date, there are very few molecules with any activity towards Cryptococcus neoformans, leading to heightened interest in finding new alternatives or adjuvants to conventional drugs for the treatment of mycosis caused by this yeast. Since the essential oils (EOs) are considered as a potential rich source of bioactive antimicrobial compounds, we evaluated the antifungal activity of Origanum vulgare (oregano), Pinus sylvestris (pine), and Thymus vulgaris (thyme red) EOs, and their components (α-pinene, carvacrol, thymol) compared with fluconazole, itraconazole, and voriconazole, against C.neoformans clinical strains. Then, we investigated the effect of EOs and components in combination with itraconazole. Methods EO composition was analysed by Gas chromatography-mass spectrometry (GC-MS). A broth microdilution method was used to evaluate the susceptibility of C.neoformans to azoles, EOs and components. Checkerboard tests, isobolograms and time-kill assays were carried out for combination studies. Results Six C.neoformans isolates were susceptible to azoles, while one C.neoformans exhibited a reduced susceptibility to all tested azole drugs. All EOs exerted a good inhibitory activity against all C.neoformans strains. Pine EO was the most effective. Among components, thymol exerted the most remarkable activity. By checkerboard testing and isobolographic analysis, combinations of itraconazole with oregano, pine, or thyme EOs, and carvacrol were found to be synergistic (FICI≤0.5) against azole susceptible C.neoformans. Regarding the azole not susceptible C.neoformans strain, the synergistic effect with itraconazole was observed with thyme EO (chemotype: thymol 26.52%; carvacrol 7.85%), and carvacrol. Time-kill assays confirmed the synergistic effects of itraconazole and oregano or thyme EO against azole susceptible C.neoformans. Binary mixtures of itraconazole/thyme EO or carvacrol yielded additive effects on the azole not susceptible C.neoformans. Conclusions Our findings highlight the potential effectiveness of thyme, oregano EOs, and carvacrol as natural and cost-effective adjuvants when used in combination with itraconazole. Identification of EOs exerting these effects could be one of the feasible ways to overcome drug resistance, reducing drug concentration and side effects.

The epidemiology of yeast infections and resistance to available antifungal drugs are rapidly increasing, and non-albicans Candida species and rare yeast species are increasingly emerging as major opportunistic pathogens. In order to identify new strategies to counter the threat of antimicrobial resistant microorganisms, essential oils (EOs) have become an important potential in the treatment of fungal infections. EOs and their bioactive pure compounds have been found to exhibit a wide range of remarkable biological activities. We investigated the in vitro antifungal activity of nine commercial EOs such as Thymus vulgaris (thyme red), Origanum vulgare (oregano), Lavandula vera (lavender), Pinus sylvestris (pine), Foeniculum vulgare (fennel), Melissa officinalis (lemon balm), Salvia officinalis (sage), Eugenia caryophyllata (clove) and Pelargonium asperum (geranium), and some of their main components (α-pinene, carvacrol, citronellal, eugenol, γ-terpinene, linalool, linalylacetate, terpinen-4-ol, thymol) against non-albicans Candida strains and uncommon yeasts. The EOs were analyzed by GC-MS, and their antifungal properties were evaluated by minimum inhibitory concentration and minimum fungicidal concentration parameters, in accordance with CLSI guidelines, with some modifications for EOs. Pine exhibited strong antifungal activity against the selected non-albicans Candida isolates and uncommon yeasts. In addition, lemon balm EOs and α-pinene exhibited strong antifungal activity against the selected non-albicans Candida yeasts. Thymol inhibited the growth of all uncommon yeasts. These data showed a promising potential application of EOs as natural adjuvant for management of infections by emerging non-albicans Candida species and uncommon pathogenic yeasts.

Over the past 20–30 years, Trichophyton rubrum represented the most widespread dermatophyte with a prevalence accounting for 70% of dermatophytosis. The treatment for cutaneous infections caused by Trichophyton spp. are imidazoles (ketoconazole (KTZ)) and triazoles (itraconazole (ITZ)). T. rubrum can develop resistance to azoles after prolonged exposure to subinhibitory concentrations resulting in therapeutic failures and chronic infections. These problems have stimulated the search for therapeutic alternatives, including essential oils, and their potential use in combination with conventional antifungals. The purpose of this study was to evaluate the antifungal activity of tea tree oil (TTO) (Melaleuca alternifolia essential oil) and the main components against T. rubrum and to assess whether TTO in association with KTZ/ITZ as reference drugs improves the antifungal activity of these drugs. We used a terpinen-4-ol chemotype (35.88%) TTO, and its antifungal properties were evaluated by minimum inhibitory and minimum fungicidal concentrations in accordance with the CLSI guidelines. The interaction between TTO and azoles was evaluated through the checkerboard and isobologram methods. The results demonstrated both the fungicide activity of TTO on T. rubrum and the synergism when it was used in combination with azoles. Therefore, this mixture may reduce the minimum effective dose of azole required and minimize the side effects of the therapy. Synergy activity offered a promise for combination topical treatment for superficial mycoses.

The aim of this study was to evaluate the influence of tea tree oil (TTO) and “Mentha of Pancalieri” essential oil (MPP) on intracellular killing of Candida krusei, often resistant to conventional drugs, by polymorphonuclear leucocytes (PMNs). Intracellular killing was investigated by incubating yeasts and PMNs with essential oils (EOs) at 1/4 and 1/8 × MIC (Minimal Inhibitory Concentration), in comparison with anidulafungin, used as a reference drug. Killing values were expressed as Survival Index (SI) values. The cytotoxicity of EOs was evaluated by 3-[4,-5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Both EOs were more efficaceous at 1/8 × MIC than 1/4 × MIC, with killing values higher than observed in EO-free systems and in presence of anidulafungin, indicating that the decreasing concentrations did not cause lower candidacidal activity. This better activity at 1/8 × MIC is probably due to the EOs’ toxicity at 1/4 × MIC, suggesting that at higher concentrations EOs might interfere with PMNs functionality. TTO and MPP at 1/8 × MIC significantly increased intracellular killing by PMNs through their direct action on the yeasts (both EOs) or on phagocytic cells (MPP), suggesting a positive interaction between EOs and PMNs to eradicate intracellular C. krusei. These data showed a promising potential application of TTO and “Mentha of Pancalieri” EO as natural adjuvants in C. krusei infection management.

The promising antimicrobial activity of essential oils (EOs) has led researchers to use them in combination with antimicrobial drugs in order to reduce drug toxicity, side effects, and resistance to single agents. Mentha x piperita, known worldwide as “Mentha of Pancalieri”, is produced locally at Pancalieri (Turin, Italy). The EO from this Mentha species is considered as one of the best mint EOs in the world. In our research, we assessed the antifungal activity of “Mentha of Pancalieri” EO, either alone or in combination with azole drugs (fluconazole, itraconazole, ketoconazole) against a wide panel of yeast and dermatophyte clinical isolates. The EO was analyzed by GC-MS, and its antifungal properties were evaluated by minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) parameters, in accordance with the CLSI guidelines, with some modifications. The interaction of EO with azoles was evaluated through the chequerboard and isobologram methods. The results suggest that this EO exerts a fungicidal activity against yeasts and a fungistatic activity against dermatophytes. Interaction studies with azoles indicated mainly synergistic profiles between itraconazole and EO vs. Candida spp., Cryptococcus neoformans, and Trichophyton mentagrophytes. Thus, the “Mentha of Pancalieri” EO may act as a potential antifungal agent and could serve as a natural adjuvant for fungal infection treatment.