Interaction of carvacroland voriconazole against drug – resistant Candida strains isolated from patients with candidiasis

Objective

Terpenoid phenols, especially 5-isopropyl-2-methylphenol (carvacrol), are components of plant essential oils that exhibit potent antifungal activity against a wide range of pathogens, including Candida species. The purpose of this study was to determine the interaction activity of carvacrol in combination with voriconazole against Candida albicans (C. albicans), C. glabrata and C. krusei isolates.

Chemical composition,antioxidant activity and antifungal effects of five Iranian essential oils against Candida strains isolated from urine samples

Systemic candidiasis has become an emerging fungal infection in recent years. Anti-Candida resistance to conventional antifungal agents has subsequently increased. This study reported the chemical composition, antioxidant and anti-Candida activity of Origanum majorana, Artemisia dracunculus, Cymbopogon citrate, Cinnamomum verum and Caryophyllus aromaticus essential oils. Different Candida species, from urine tracts of hospitalized patients, were included to be challenged with understudied essential oils. Chemical compositions were determined using gas chromatography/mass spectroscopy (GC/MS) analysis and antioxidant activity was measured using DDPH assay. MIC of these essential oils was evaluated using broth micro-dilution test. Caryophyllus aromaticus had the highest antioxidant activity while the lowest antioxidant activity was for Artemisia dracunculus. MICs of Cinnamomum verum, Caryophillium aromaticus, Artemisia dracunculus, Origanum vulgare and Cymbopogon citratus essential oils ranged from 125 to 175 μg/mL (mean value: 147.7 ± 25.5 μg/mL), 700 to 1000 μg/mL (mean value: 740.9 ± 105.4 μg/mL), 1000 to 2000 μg/mL (mean value: 1454.5 ± 509.6 μg/mL), 173 to 350 μg/mL (mean value: 208 ± 55.8 μg/mL) and 125 to 175 μg/mL (mean value: 156.8 ± 24.6 μg/mL) for different Candida species, respectively. In general, natural compounds are suitable to be used as anti-Candida and antioxidant agents. However in this stage, these compounds could be applied as supplementary agents along with conventional antifungal drugs.     

In vitro susceptibility of Candida spp. to fluconazole,itraconazole and voriconazole and the correlation between triazoles susceptibility: Results from a five-year study

Candida spp. is a common cause of invasive fungal disease. The aim of this study was to examine the susceptibility of Candida spp. to fluconazole, itraconazole and voriconazole and explore the correlation between triazoles susceptibility. The antifungal susceptibility in the present study was measured by ATB Fungus 3 method, and the potential relationship was examined by obtaining the correlation of measured minimal inhibitory concentrations (MICs) of Candida spp. isolates. A total of 2099 clinical isolates of Candida spp. from 1441 patients were analyzed. The organisms included 1435 isolates of Candida albicans, 207 isolates of Candida glabrata, 65 isolates of Candida parapsilosis, 31 isolates of Candida krusei, 268 isolates of Candida tropicalis. Voriconazole and itraconazole were more active than fluconazole and against Candida spp. in vitro. The fluconazole, itraconazole and voriconazole MIC₉₀ (MIC for 90% of the isolates) for all Candida spp. isolates was 4 mg/L, 1 mg/L and 0.25 mg/L, respectively. There was a moderate correlation between the fluconazole MIC_s for Candida spp. isolates and this for voriconazole (R² = 0.475; P < 0.01) and itraconazole (R² = 0.431; P < 0.01). Voriconazole MICs for the Candida spp. isolates also correlated with those for itraconazole (R² = 0.401; P < 0.01). These observations suggest that the in vitro susceptibility of Candida spp. to fluconazole, itraconazole and voriconazole exhibits a moderate correlation.     

Molecular identification and antifungal susceptibility testing of Candida species isolated from dental plaques

Objective

The aim of the present study was to provide insight into the prevalence and susceptibility profiles of Candida species isolated from the dental plaque of Iranian immunocompetent patients. As a biofilm, Candida species are responsible for several disorders common to the oral cavity including gingivitis, dental caries, periodontitis, and the less common severe systemic infections specifically in immunosuppressed individuals.

Synthesis,characterization and antifungal activity of a novel formulated nanocomposite containing Indolicidin and Graphene oxide against disseminated candidiasis

Objective

Candidiasis is one of the most opportunistic fungal infections in immunocompromised patients. The emergence of multidrug-resistant Candida species necessitates the development of novel antifungal agents. Seeking to the discovery of natural antifungal agents, this study aimed to synthesize a novel formulated nanocomposite containing Indolicidin (IN), antimicrobial peptide, and Graphene oxide (GO), kind of nanomaterial, against Candida growth using in vitro and in vivo experiments for the first time.

In vitro activity of antifungal combinations against planktonic and sessile cells of Candida albicans isolated from medical devices in an intensive care department

Background

Invasive fungal infections are an emerging health problem worldwide. They are responsible for a significant rate of morbidity and mortality. Infections caused by Candida albicans involve proliferation of biofilms on biotic or abiotic surface. These adherent communities exhibit characteristics distinct from planktonic cells such as the ability to tolerate high concentrations of antifungal.

Evaluation of biofilm formation ability in different Candida strains and anti-biofilm effects of Fe3O4-NPs compared with Fluconazole: an in vitro study

Objective

Biofilm formation ability is one of the major virulence factors contributing to the pathogenesis of Candida species. Biofilms produced by Candida spp. cause complicated treatments and contribute to increasing unpleasant mortality rates. Nanoparticles of Fe₃O₄ (Fe₃O₄-NPs) are considered due to their magnetic and biochemical properties, as well as their low costs. The purpose of present study was to determine biofilm formation ability in different Candida strains and evaluation of anti-biofilm effect of Fe₃O₄-NPs compared with FLC.

Isavuconazole: A new broad-spectrum azole. Part 1: In vitro activity

Triazoles compounds are first-line agents for the treatment of invasive fungal diseases. Isavuconazole is the most recent triazole compound, approved in 2015 by the FDA and the EMA to treat invasive aspergillosis and mucormycosis. We reviewed here the in vitro activity of isavuconazole against a vast spectrum of species. Isavuconazole MICs were evaluated using CLSI, EUCAST or Etest methods, with no significant differences between the technics. Low MIC₅₀ and MIC₉₀ (< 1 μg/mL) were described for isavuconazole against the majority of Candida spp., except for C. glabrata and C. krusei. In vitro activity against Aspergillus spp. varied according to the species with an overall MIC₉₀ of 1 μg/mL ranging from 0.125 μg/mL (A. fumigatus) to 16 μg/mL (A. niger, A. tubingiensis). As for Aspergillus, the activity of isavuconazole against agents of mucormycosis varies upon genus and species, with an overall MIC₉₀ from 4 (Rhizopus spp.) to 16 μg/mL (Rhizomucor spp. and Mucor spp.). Recently, to help detecting non-wild-type isolates, EUCAST committee has proposed ECOFFs values for C. albicans, C. parapsilosis and C. tropicalis (0.03 μg/mL), for Aspergillus fumigatus (2 μg/mL), A. nidulans (0.25 μg/mL), A. terreus (1 μg/mL), A. flavus (2 μg/mL) and A. niger (4 μg/mL). Moreover, clinical breakpoints (susceptible/resistant) were defined for Aspergillus fumigatus (1 μg/mL), A. nidulans (0.25 μg/mL) and A. terreus (1 μg/mL). Using these breakpoints, isavuconazole showed activity against the vast majority of fungi.     

Anti-Candida activity of the water-soluble lectin from Moringa oleifera seeds (WSMoL)

This work reports the effects of the water-soluble lectin from Moringa oleifera seeds (WSMoL) on growth and survival of Candida species. In addition, cellular alterations linked to the antifungal effect were investigated. The minimal inhibitory (MIC) and fungicidal (MFC) concentrations were determined and 24-h growth curves in absence and presence of lectin were established. Flow cytometry was used to evaluate the induction of apoptosis/necrosis, alterations in mitochondrial membrane potential (ΔΨm), and occurrence of lysosomal damage. WSMoL inhibited the growth of C. albicans, C. glabrata, C. krusei and C. parapsilosis with MIC of 20 μg/mL. The lowest MFC (20 μg/mL) was detected for C. glabrata and the highest (80 μg/mL) for C. albicans and C. parapsilosis. The inhibitory effect started from the ninth to nineteenth hour of incubation depending on the fungal species. Incubation with the lectin at the MIC for 24 h increased the number of cells undergoing apoptosis and necrosis. Hyperpolarization of the mitochondrial membrane was detected after 12-h treatment, followed by reduction of ΔΨm or depolarization after 24 h. No lysosomal damage was detected in treated cells. In conclusion, WSMoL is a fungistatic and fungicide agent against Candida with differential effects depending on the species.     

Anticandidal synergistic activity of Ocimum sanctum and fluconazole of azole resistance strains of clinical isolates

Candida albicans is the most prevalent fungal pathogen in humans. It is the causative agent and most associated with serious fungal infection, accounting for more than 90% of cases. It is a most common cause of deep mycoses and vulvovaginal candidiasis. In the present study we found that methanolic extract of O. sanctum in combination of fluconazole shows higher zone of inhibition and lesser MIC values as compared to methanolic extract of leaves of O. sanctum or fluconazole when used alone. Synergistic antimicrobial activity was found when methanolic extract of leaves of O. sanctum was used in combination with fluconazole against C. albicans azole resistance strains isolated from catheter tip (CT) and high vaginal swab (HVS) (FIC ≤ 0.5). Partial synergistic activity was observed against urine (U). Methanolic extract of stem of O. sanctum in combination with fluconazole gave indifferent antifungal results (FIC = 1.0–4.0). Benzene extract of the leaf and stem of O. sanctum in combination with fluconazole showed indifferent antifungal results (FIC = 1.0–4.0). Aqueous extract of leaves of O. sanctum in combination with fluconazole showed partial synergistic antimicrobial activity against catheter tip (CT) and high vaginal swab (HVS) and urine (U) (FIC = 0.5–1.0). In the present study we evaluate the synergism of C. albicans against azole resistant clinical isolates. This study indicates clear evidence supporting the traditional use of O. sanctum in treating Candida infectious diseases.     

Species identification and in vitro antifungal susceptibility testing of Aspergillus section Nigri strains isolated from otomycosis patients

Introduction

Aspergillus niger is the most commonly reported etiology of otomycosis based on morphological characteristics. This fungus is a member of Aspergillus section Nigri, a set of morphologically indistinguishable species that can harbor various antifungal susceptibility patterns. The aim of this study was to accurately identify and determine the susceptibility pattern of a set of black aspergilli isolated from otomycosis patients.

Antifungal susceptibility of oral isolates of Candida species from chronic kidney disease patients on chronic dialysis

Chronic renal disease patients under chronic dialysis (CRDD) have a multifactorial immunological deterioration with an increased risk of Candida infections. Incidence of Candida infections is increasing. Choice of suitable antifungal agents is limited due to the resistance of some species to several antifungals. Aim of the present study was to identify the distribution and antifungal susceptibility patterns of oral isolated Candida species from infected and colonized patients, as well as to investigate the risk factors for oral infection in patients on dialysis. Cross-sectional study, approved by the institutional bioethics committees was performed in CRDD patients. Demographic, clinic data, and oral mucosa samples were obtained. Infection diagnosis was established clinically and confirmed with exfoliative cytology, each sample was plated on CHROMagar Candida and incubated at 36 °C for 2 days. Yeast species were identified by carbohydrate assimilation ID 32 C AUX system and the apiweb database. For the antifungal susceptibility test, the M44 A-3 method (CLSI) using fluconazole (FCZ), miconazole (MCZ), nystatin (NYS), and voriconazole (VCZ). Study included 119 participants, the main cause of CRD was nephropathy due to DM2 (58%), and three-fourths of the patients were under hemodialysis. Candida prevalence was 56.3% of 67 colonized or infected patients, 88 isolates were obtained. Principal identified species were C. albicans (51.1%), C. glabrata (25%), and C. tropicalis (14.8%). C. glabrata showed a reduced response to FCZ in 50% of isolates and C. albicans had a reduced response in 16% of the isolates. Antifungal agent with the least efficacious response or with the lowest susceptibility in the isolates of these patients was MCZ, followed by VCZ and FCZ, whereas NYS induced the best antifungal response.     

Potential effect of 2-isopropyl-5-methylphenol (thymol) alone and in combination with fluconazole against clinical isolates of Candida albicans,C. glabrata and C. krusei

Limitations of antifungals used in the treatment of candidiasis, as the development of resistant strains, are known by the scientific community. In this context, the aim of this study was to investigate the activity of 2-isopropyl-5-methylphenol (thymol) in combination with fluconazole (FLZ) against clinical Candida strains. The antifungal activity of thymol along with FLZ was evaluated by the Clinical Laboratory Standards Institute (CLSI) M27-A2 broth microdilution method. In addition, synergism was observed for clinical strains of Candida spp. with combination of thymol-FLZ evaluated by the chequerboard microdilution method. The mean of minimum inhibitory concentration (MIC) values of thymol and FLZ were 49.37 and 0.475 μg/ml for C. albicans, 51.25 and 18.80 μg/ml for C. glabrata and 70 and 179.20 μg/ml for C. krusei strains, respectively. Thymol in combination with FLZ exhibited the synergistic effects against all species of Candida tested. FICI values for thymol plus FLZ ranged from 0.366 to 0.607 for C. albicans strains, 0.367 to 0.482 for C. glabrata strains, and 0.375 to 0.563 for C. krusei strains. No antagonistic activity was seen in the strains tested. Thymol was found to have a fungicidal effect on Candida species and a synergistic effect when combined with FLZ.     

Mode of action and anti-Candida activity of Artemisia annua mediated-synthesized silver nanoparticles

Candida albicans is a polymorphic opportunistic commensal that causes both superficial and systemic fungal infections especially in immunocompromised patients. Biologically synthesized silver nanoparticles (AgNPs) have emerged as potential antifungal agents. The present work evaluates the antifungal activity of Artemisia annua synthesized AgNPs against three Candida species (C. albicans ATCC 90028, C. tropicalis ATCC 750 and C. glabrata ATCC 90030). The in vitro effect of AgNPs was investigated for fungal growth, sterol content, secretion of hydrolytic enzymes and yeast-to-hyphal transition. The green synthesized AgNPs were effective against all the three species with minimum inhibitory concentration (MIC) in the range 80–120 μgml⁻¹. Candida glabrata showed greater sensitivity for AgNPs followed by Candida tropicalis and C. albicans. AgNPs at 4MIC were as effective as fluconazole (FLC) and caused only 5% haemolysis while FLC caused 50% haemolysis at the same concentration. The secretion of hydrolytic enzymes was the lowest in case of AgNP exposed C. glabrata. Yeast-to-hyphal transition was significantly reduced in treated C. albicans cells and showed disfigured morphology in SEM images. The decrease in ergosterol content was slightly higher (94%) in both C. glabrata and C. tropicalis in comparison to C. albicans (69%). Green synthesized AgNPs thus have immense potential as an antifungal and can play a crucial role in the management of Candida infections especially those caused by C. glabrata.     

Montivipera bornmuelleri venom selectively exhibits high cytotoxic effects on keratinocytes cancer cell lines

Context

The Viperidae family venom is a rich source of bioactive compounds such as many proteases, which cause tissue necrosis and affect mostly the vascular system. However, the venom exhibits therapeutic potentials and has contributed to the development of some medical drugs. Specifically, the Montivipera bornmuelleri venom has shown to exhibit antibacterial, pro-inflammatory and antifungal activities.

Comparative analysis of proteinase,phospholipase, hydrophobicity and biofilm forming ability in Candida species isolated from clinical specimens

Candida species are the commensal organisms of human and animal mucosa that cause a wide range of debilitating diseases in immunocompromised patients and other susceptible individuals. The present study aimed to investigate the ability of clinical isolates of various Candida species to produce proteinase and phospholipase, hydrophobicity and biofilm forming ability that assumed to have a vital role in Candida pathogenicity. Eighty-four Candida strains belonged to Candida albicans (44.1%), C. glabrata (5.9%), C. guilliermondii (5.9%), C. krusei (10.8%), C. parapsilosis (26.2%), and C. tropicalis (7.1%) were examined for proteinase and phospholipase production, cell surface hydrophobicity and biofilm forming ability. The production of proteinase and phospholipase was detected in 81 (96.4%) and 79 (94.1%) of the strains, respectively. C. albicans showed the highest proteinase and phospholipase activity (mean Pz values of 0.42 ± 0.25 and 0.72 ± 0.28) and biofilm formation ability (0.66 ± 0.22). C. parapsilosis had the highest hydrophobicity (42.97 ± 16.1), which showed a good correlation with biofilm formation ability. A considerable percentage of non-albicans Candida strains produced significant amounts of proteinase and phospholipase with a good ability of biofilm formation in vitro. Taken together, our results further substantiated that enzymatic activity, hydrophobicity and the ability for biofilm formation are important virulence factors which may be account for pathogenicity of various Candida species distributed in albicans and non-albicans groups.     

Susceptibility profile of Candida rugosa (Diutina rugosa) against antifungals and compounds of essential oils

Candida rugosa (recently reclassified Diutina rugosa) is an emerging pathogen affecting humans and animals. Candida resistance to existing drugs is an important factor to be monitored, as well as the need of researching alternatives to conventional antifungals. Here, we evaluated the in vitro effects of some antifungals and major components of essential oils by the broth microdilution method (CLSI M27-A3) against fifteen C. rugosa strains from animals isolated and molecular identificated. The results showed MIC₉₀ of: 0.125 μg/mL to ketoconazole and voriconazole, 0.25 μg/mL to micafungin, 0.5 μg/mL to anidulafungin, 1 μg/mL to caspofungin, 2 μg/mL to amphotericin B, itraconazole and flucytosin, 8 μg/mL to fluconazole, 16 μg/mL to nystatin and >128 μg/mL to terbinafine. The compounds carvacrol (MIC₉₀ 320 μg/mL), thimol (MIC₉₀ 320 μg/mL) and cinnamaldehyde (MIC₉₀ 160 μg/mL) demonstrated antifungal activity against the samples tested.     

Antifungal and antibacterial activity of densely dispersed silver nanospheres with homogeneity size which synthesized using chicory: An in vitro study

With increase in isolation of multi and extensive drug resistance hospital pathogens (MDR, XDR) in burn centers of many hospitals in the world, attempt to use nanomaterials for treatment of burn-infected patients is the focus of researches all around the world. In the present investigation silver nanospheres (Ag NSs) has been synthesized by chicory seed exudates (CSE). The various parameters influencing the mechanism of Ag NSs synthesis including temperature, concentration, pH and time were studied. Greener Ag NSs were formed when the reaction conditions were altered with respect to pH, concentration of AgNO₃ and incubation temperature. Finally, we evaluated antimicrobial activity of silver nanospheres biosynthesized by chicory (Cichodrium intybus) against most prevalent burn bacteria pathogens Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, and fungus Fusarium solani. The UV visible spectroscopy, X-Ray diffraction (XRD), dynamic light scattering (DLS) used for primary screening of physicochemical properties. The transmission electron microscopy (TEM) images showed the Ag NSs (with globular shape) with a size less than 25 nm that they have the same size about 8 nm (more than 97% are 8 nm). Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of Ag NSs against the standard strains of A. baumannii, P. aeruginosa and K. pneumonia showed a relatively high inhibitory and bactericidal activity (MIC 1.56 μg/mL and MBC 3.12 μg/mL) of the nanoparticles and F. solani cultures. In antifungal tests, the lowest level of zone of inhibition was observed at a concentration of 5 μg/mL synthesized silver nanospheres with the 7% inhibition of growth. Ag NSs have high antimicrobial activity against three common burn bacteria pathogens and fungus F. solani. Therefore, Ag NSs can be used to prevent burn infection and for wound healing.     

Antifungal activity of toothpastes against oral Candida isolates

Many types of toothpaste have been formulated over recent years to contain antimicrobial compounds with the aim of preventing or reducing plaque, calculus, gingivial inflammation or dental caries. Different brands have their own composition and concentration of ingredients for their efficacy. In this study, the anticandidal activity of six different toothpastes containing the following active ingredients: sodium fluoride, sodium monofluorophosphate, triclosan and herbal compounds were investigated against eight Candida species [Candida glabrata (n = 35), Candida albicans (n = 25), Candida krusei (n = 10), Candida tropicalis (n = 9), Candida pseudotropicalis (n = 7), Geotrichum candidum (n = 7), Candida lipolytica (n = 5), and Candida lusitaniae (n = 4)], isolated from oral cavities and denture using the agar-diffusion test. Five toothpastes were effective in inhibiting the growth of all Candida species, while one toothpaste was not effective against C. tropicalis, C. pseudotropicalis and C. lusitaniae. The herbal toothpaste exhibited good antifungal activity against all Candida species.