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Invasive infections caused by non-albicans Candida are increasing worldwide. However, there is still a lack of information on invasive candidiasis (IC) in the pediatric setting, including susceptibility profiles and clonal studies. We investigated the clinical, epidemiologic, and laboratory characteristics of IC, possible changes in antifungal susceptibility profiles over time, and the occurrence of clonality in our tertiary children's hospital. We analyzed 123 non-duplicate Candida isolates from sterile sites of pediatric patients in a tertiary hospital in southern Brazil, between 2016 and 2021. Data on demographics, comorbidities, and clinical outcomes were collected. Candida species distribution, antifungal susceptibility profiles, biofilm production, and molecular epidemiology of isolates were assessed using reference methods. The range of IC incidence was 0.88-1.55 cases/1000 hospitalized patients/year, and the IC-related mortality rate was 20.3%. Of the total IC cases, 42.3% were in patients aged < 13 months. Mechanical ventilation, parenteral nutrition, and intensive care unit (ICU) admission were common in this group. In addition, ICU admission was identified as a risk factor for IC-related mortality. The main site of Candida spp. isolation was blood, and non-albicans Candida species were predominant (70.8%). No significant clonal spread was observed among isolates of the three most commonly isolated species, and 99.1% of all isolates were biofilm producers. Non-albicans Candida species were predominant in this study. Notably, clonal expansion and emergence of antifungal drug resistance were not observed in our pediatric setting.
The epidemiology of invasive candidiasis has changed over time and there is still a lack of information in the pediatric setting. Non-albicans Candida species predominated in this study, clonal expansion and emergence of antifungal drug resistance were not observed in our pediatric setting.
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Antifúngicos , Candida , Candidiasis Invasiva , Pruebas de Sensibilidad Microbiana , Centros de Atención Terciaria , Humanos , Centros de Atención Terciaria/estadística & datos numéricos , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Candidiasis Invasiva/microbiología , Candidiasis Invasiva/mortalidad , Candidiasis Invasiva/epidemiología , Lactante , Masculino , Femenino , Brasil/epidemiología , Preescolar , Candida/efectos de los fármacos , Candida/aislamiento & purificación , Candida/clasificación , Niño , Hospitales Pediátricos/estadística & datos numéricos , Biopelículas/crecimiento & desarrollo , Biopelículas/efectos de los fármacos , Incidencia , Farmacorresistencia Fúngica , Adolescente , Recién Nacido , Factores de Riesgo , Estudios RetrospectivosRESUMEN
Aim: To evaluate the antifungal activity of amlodipine against strains of Candida spp. and to its possible mechanism of action.Methods: Broth microdilution tests were used to determine the minimum inhibitory concentration, while the synergistic activity was evaluated by calculating the fractional inhibitory concentration index. The action of amlodipine against biofilms was determined using the MTT assay and its possible mechanism of action was investigated through flow cytometry tests.Results: Amlodipine showed MICs ranging from 62.5 to 250 µg/ml, in addition to action against pre-formed and forming biofilms, with reductions between 50 and 90%. Amlodipine increases the externalization of phosphatidylserine and reduces the cell viability of fungal cells, suggesting apoptosis.Conclusion: Amlodipine had good antifungal activity against planktonic cells and biofilms of Candida spp., by leading the cells to apoptosis.
Candida is a type of fungus that can cause diseases. This fungus became stronger over time and drugs can no longer kill them easily, so it is important to find new drugs. We decided to study whether amlodipine, a drug used for heart disease, has action against Candida. We discovered that amlodipine make fungi weaker. We still need to do more studies to find out if amlodipine can help prevent Candida diseases.
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Amlodipino , Antifúngicos , Biopelículas , Candida , Pruebas de Sensibilidad Microbiana , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Antifúngicos/farmacología , Candida/efectos de los fármacos , Candida/fisiología , Candida/crecimiento & desarrollo , Amlodipino/farmacología , Viabilidad Microbiana/efectos de los fármacos , Apoptosis/efectos de los fármacos , Humanos , Citometría de Flujo , Plancton/efectos de los fármacos , Plancton/crecimiento & desarrolloRESUMEN
Aim: Evaluate the anticandidal effect of Croton heliotropiifolius Kunth essential oil and its interaction with azoles and N-acetylcysteine (NAC) against planktonic cells and biofilms.Materials & methods: Broth microdilution and checkerboard methods were used to evaluate the individual and combined activity with fluconazole and itraconazole (ITRA). The antibiofilm effect of the oil was assessed in 96-well plates alone and combined with ITRA and NAC, and cytotoxicity determined by MTT.Results: The oil inhibited all Candida species growth. The activity was enhanced when associated with ITRA and NAC for planktonic cells and biofilms in formation. The effective concentrations were lower than the toxic ones to V79 cells.Conclusion: C. heliotropiifolius Kunth essential oil is an anticandidal alternative, and can be associated with ITRA and NAC.
Candida is a type of fungus that can cause disease in people. In recent years, the number of available drugs to treat this disease have declined. It is important to search for new drugs. Plants are often used to improve health, so we tested the essential oil of a plant called Croton heliotropiifolius to see if it could kill the fungus. We found that the essential oil could kill the fungus, and could be used with other drugs to improve their effects.
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Acetilcisteína , Antifúngicos , Biopelículas , Candida , Croton , Itraconazol , Pruebas de Sensibilidad Microbiana , Aceites Volátiles , Croton/química , Aceites Volátiles/farmacología , Aceites Volátiles/química , Itraconazol/farmacología , Antifúngicos/farmacología , Acetilcisteína/farmacología , Biopelículas/efectos de los fármacos , Candida/efectos de los fármacos , Sinergismo Farmacológico , Animales , Línea Celular , Fluconazol/farmacología , CricetinaeRESUMEN
The skin of patients with atopic dermatitis (AD) has a greater diversity of mycobiota. An observational, prospective, cross-sectional, analytical, and comparative study was conducted involving 80 patients with AD Group (ADG) and 50 individuals without AD (wADG) in a tertiary hospital in Brazil. Skin scale samples were collected from the frontal, cervical, fossae cubital, and popliteal regions and identified using molecular biology techniques. The results showed that 47.5% of ADG had identified yeasts compared to 0% of wADG (P < .001). The yeasts Rhodotorula mucilaginosa and Candida parapsilosis were the most abundant. The probability of colonization increased with age, showing values of 40% at 60 months and 80% at 220 months (P = .09). The cervical region (12.5%) was colonized to the greatest extent. Our findings revealed that positive mycology was not more probable when the scoring of atopic dermatitis or eczema area and severity index value increased (P = .23 and .53, respectively). The results showed that the sex, age, and different population types directly affected the composition of the mycobiota in the population analyzed. A higher frequency of colonization and greater diversity of yeast species were detected in the cutaneous mycobiota of children with AD.
Atopic dermatitis (AD) is a skin disease that can be colonized by microorganisms. We evaluated patients with and without the disease and found a higher frequency of colonization by Rhodotorula mucilaginosa and Candida parapsilosis on the skin of children with AD.
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Dermatitis Atópica , Piel , Levaduras , Humanos , Dermatitis Atópica/microbiología , Masculino , Femenino , Preescolar , Niño , Estudios Prospectivos , Estudios Transversales , Brasil , Levaduras/aislamiento & purificación , Levaduras/clasificación , Levaduras/genética , Adolescente , Lactante , Piel/microbiología , Micobioma , Centros de Atención TerciariaRESUMEN
Candida species are among the priority pathogens in the area of research and development. Due to the problems associated with resistance to antifungals, new therapeutic alternatives are necessary. In this regard, drug repositioning has gained prominence. The objective of this study was to evaluate the activity of three tricyclic antidepressants (TCAs) - amitriptyline (AMT), nortriptyline (NOR) and clomipramine (CLO) - isolated or associated with antifungals against strains of Candida spp., as well as to analyze the possible mechanism of action. Among the methods used were broth microdilution tests, tolerance level assessment, checkerboard assays, flow cytometry and fluorescence microscopy. Furthermore, Candida cells were visualized after treatments by scanning electron microscopy (SEM). AMT presented MIC 50% in the range of 16 to 128 µg/mL, NOR from 8 to 128 µg/mL, and CLO from 8 to 64 µg/mL, with all three TCAs having a fungicidal inhibitory action profile. For these TCAs, there was synergism with amphotericin B (AMB) in 100% of the isolates. In association with fluconazole (FLC) and itraconazole (ITR), there were mostly indifferent interactions. TCAs isolated and associated with AMB reduced cell viability, promoted DNA fragmentation and damage, caused mitochondrial depolarization, externalization of phosphatidylserine, produced reactive oxygen species (ROS), decreased reduced glutathione (GSH) and increased carbonyl protein levels, causing morphological changes. The results suggest the antifungal mechanism of the TCAs works via the apoptotic pathway.
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The increase in fungal resistance is a major public health concern. In this context, Candida spp. is an important genus related to invasive diseases, especially in immunosuppressed patients. The relevance of alternative approaches to increasing fungal resistance stands out, in which products of natural origin demonstrate potential antifungal activity in vitro against Candida spp. In this sense, this work aimed to evaluate the in vitro activity of tannic acid against Candida spp. Minimum inhibitory concentration (MIC) was determined for tannic acid and the antifungals, and the checkerboard assay was performed to analyze the interactions between them. Furthermore, we evaluated the tannic acid antibiofilm activity and its possible mechanism of action. Tannic acid showed MIC ranging to 0.06 to 0.5 µg/ml and showed no loss of effectiveness when combined with antifungals. Also, is safe at the concentrations it exerts its antifungal activity in pre-formed biofilms, as demonstrated by IC50 in murine fibroblasts cells and the hemolytic assay. Additionally, its mechanisms of action can be related with induction of signals that lead to apoptosis in fungal cells.
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The use of recreational waters is a widespread activity worldwide, and one of the risks associated with this practice is the exposure of bathers to microorganisms that may arise due to pollution caused by inadequate infrastructure and sanitation. In the present work, we isolated Candida spp. (n = 24) from five recreational beaches in Rio de Janeiro, Brazil, in order to evaluate their susceptibility to antifungals, the production of virulence attributes and the in vivo virulence using Tenebrio molitor larvae as a model. The ITS1-5.8S-ITS2 gene sequencing identified thirteen isolates (54.1 %) as C. tropicalis, seven (29.1 %) as C. krusei (Pichia kudriavzevii), one (4.2 %) as C. rugosa (Diutina rugosa), one (4.2 %) as C. mesorugosa (Diutina mesorugosa), one (4.2 %) as C. utilis (Cyberlindnera jadinii) and one (4.2 %) as C. parapsilosis. C. tropicalis isolates showed resistance to azoles and susceptibility to amphotericin B, flucytosine and caspofungin. C. krusei isolates were resistant to fluconazole, caspofungin and itraconazole, with 42.8 % resistance to flucytosine, besides susceptibility to voriconazole and amphotericin B. The remaining species were susceptible to all tested antifungals. All Candida isolates adhered to abiotic surfaces and formed biofilm on polystyrene, albeit to varying degrees, and produced aspartic protease and hemolytic activity, which are considered fungal virulence attributes. C. tropicalis, C. krusei and C. utilis isolates produced phytase, while the only esterase producer was C. tropicalis. Regarding resistance to osmotic stress, all isolates of C. tropicalis, C. parapsilosis and C. mesorugosa grew up to 7.5 % NaCl; the remaining isolates grew up to 1.87-3.75 % NaCl. The mortality caused by fungal challenges in T. molitor larvae was variable, with C. tropicalis, C. utilis and C. parapsilosis being more virulent than C. krusei and C. rugosa complex. Collectively, the presence of these yeasts, particularly the virulent and resistant isolates, in recreational waters can pose a significant health risk to bathers.
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Antifúngicos , Candida , Farmacorresistencia Fúngica , Brasil , Antifúngicos/farmacología , Candida/efectos de los fármacos , Candida/patogenicidad , Candida/genética , Virulencia , Pruebas de Sensibilidad Microbiana , Animales , PlayasRESUMEN
Vulvovaginal candidiasis (VVC) remains a prevalent fungal disease, characterized by challenges, such as increased fungal resistance, side effects of current treatments, and the rising prevalence of non-albicans Candida spp. naturally more resistant. This study aimed to propose a novel therapeutic approach by investigating the antifungal properties and toxicity of 2-hydroxychalcone (2-HC) and 3'-hydroxychalcone (3'-HC), both alone and in combination with fluconazole (FCZ) and clotrimazole (CTZ). A lipid carrier (LC) was also developed to deliver these molecules. The study evaluated in vitro anti-Candida activity against five Candida species and assessed cytotoxicity in the C33-A cell line. The safety and therapeutic efficacy of in vivo were tested using an alternative animal model, Galleria mellonella. The results showed antifungal activity of 2-HC and 3'-HC, ranging from 7.8 to 31.2 as fungistatic and 15.6 to 125.0 mg/L as fungicide effect, with cell viability above 80% from a concentration of 9.3 mg/L (2-HC). Synergistic and partially synergistic interactions of these chalcones with FCZ and CTZ demonstrated significant improvement in antifungal activity, with MIC values ranging from 0.06 to 62.5 mg/L. Some combinations reduced cytotoxicity, achieving 100% cell viability in many interactions. Additionally, two LCs with suitable properties for intravaginal application were developed. These formulations demonstrated promising therapeutic efficacy and low toxicity in Galleria mellonella assays. These results suggest the potential of this approach in developing new therapies for VVC.
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Introduction. The development of new antifungal drugs has become a global priority, given the increasing cases of fungal diseases together with the rising resistance to available antifungal drugs. In this scenario, drug repositioning has emerged as an alternative for such development, with advantages such as reduced research time and costs.Gap statement. Propafenone is an antiarrhythmic drug whose antifungal activity is poorly described, being a good candidate for further study.Aim. This study aims to evaluate propafenone activity against different species of Candida spp. to evaluate its combination with standard antifungals, as well as its possible action mechanism.Methodology. To this end, we carried out tests against strains of Candida albicans, Candida auris, Candida parapsilosis, Candida tropicalis, Candida glabrata and Candida krusei based on the evaluation of the MIC, minimum fungicidal concentration and tolerance level, along with checkerboard and flow cytometry tests with clinical strains and cell structure analysis by scanning electron microscopy (SEM).Results. The results showed that propafenone has a 50% MIC ranging from 32 to 256 µg ml-1, with fungicidal activity and positive interactions with itraconazole in 83.3% of the strains evaluated. The effects of the treatments observed by SEM were extensive damage to the cell structure, while flow cytometry revealed the apoptotic potential of propafenone against Candida spp.Conclusion. Taken together, these results indicate that propafenone has the potential for repositioning as an antifungal drug.
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Antifúngicos , Candida , Pruebas de Sensibilidad Microbiana , Propafenona , Antifúngicos/farmacología , Candida/efectos de los fármacos , Candida/crecimiento & desarrollo , Propafenona/farmacología , Humanos , Itraconazol/farmacología , Sinergismo Farmacológico , Farmacorresistencia Fúngica/efectos de los fármacos , Candidiasis/microbiología , Candidiasis/tratamiento farmacológico , Reposicionamiento de MedicamentosRESUMEN
Abstract Objectives: Fungal infections (FI) pose a public health concern and significantly increase mortality rates, especially within Neonatal Intensive Care Units (NICU). Thus, this study aimed to investigate epidemiological indicators, risk factors, and lethality predictors associated with FI in a NICU. Methods: This study included 1,510 neonates admitted to the NICU of a reference hospital in Brazil between 2015 and 2022. Demographic data, such as sex, birth weight, gestational age, and use of invasive devices were analyzed. Results: Thirty neonates developed invasive FI, totaling 33 episodes and an incidence of 1.2 per 1,000 patient days. Candida albicans was the most frequent species (52.9 %), the bloodstream was the most affected site (78.9 %), and 72.7 % of infections occurred between 2015 and 2018. The lethality rate associated with FI was 33.3 %, and 90 % of deaths occurred within 30 days of diagnosis of infection. Weight < 750 g, prolonged hospital stay, use of parenteral nutrition, and broad-spectrum antimicrobials were independent risk factors for infection occurrence, especially glycopeptides and 4th generation cephalosporins, having a considerable role in the increase in fungal infections. Weight < 750 g was considered a significant predictor of lethality, and C. albicans had the highest lethality rate (40 %). Conclusion: These findings highlight the elevated lethality rate associated with these infections, reinforcing the importance of developing strategies to control FI within NICU.
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OBJECTIVE: This study aims to analyze the prevalence of Candida spp. colonization in oral leukoplakia and oral lichen planus lesions, verify the influence of systemic and local factors, besides identify and determine the in vitro antifungal susceptibility profile of Candida species. MATERIALS AND METHODS: Samples were collected by swabbing from oral lesions and healthy mucosa and cultured on Sabouraud Dextrose and CHROMagar® Candida plates. Species identification was confirmed with MALDI-TOF MS analysis. RESULTS: Candida spp. was found in 36.8% of cases of oral leukoplakia and 18.2% of cases of oral lichen planus. Candida albicans was the only species found in oral lichen planus lesions (n = 2, 100%) and the most prevalent in oral leukoplakia (n = 5, 76.4%). Among the non-albicans Candida species found in oral leukoplakia were C. parapsilosis (n = 2, 25.5%) and C. tropicalis (n = 1, 14.1%). Candida isolates were susceptible to all antifungals tested. CONCLUSION: C. albicans was the most commonly found species in the studied lesions. No correlation was found between systemic and local factors with positive cases of oral lichen planus. However, smoking and alcohol consumption may be associated with positive cases of oral leukoplakia, especially the non-homogeneous clinical form. In addition, there is a possible predisposition to associated Candida colonization in cases of epithelial dysplasia found in oral leukoplakia. The antifungal medications tested showed excellent efficacy against isolates.
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Antifúngicos , Candida , Leucoplasia Bucal , Liquen Plano Oral , Pruebas de Sensibilidad Microbiana , Humanos , Liquen Plano Oral/microbiología , Liquen Plano Oral/patología , Leucoplasia Bucal/microbiología , Leucoplasia Bucal/patología , Candida/efectos de los fármacos , Candida/aislamiento & purificación , Candida/clasificación , Masculino , Persona de Mediana Edad , Femenino , Antifúngicos/farmacología , Adulto , Anciano , Candidiasis Bucal/microbiología , Adulto Joven , PrevalenciaRESUMEN
The content of chemical constituents in Eugenia uniflora leaf extracts correlates positively with biological activities. The experimental objective was to carry out the phytochemical screening and purification of the major polyphenols from the leaves of E. uniflora. In addition, the anti-Candida activity of the hydroalcoholic extract, fraction, subfractions and polyphenols purified were evaluated. After partitioning of the extract with ethyl acetate, the fractions were chromatographed on Sephadex® LH-20 gel followed by RP-flash chromatography and monitored by TLC and RP-HPLC. The samples were characterized by mass spectrometry (LC-ESI-QTOF-MS2) and subjected to the microdilution method in 96-well plates against strains of C. albicans, C. auris, and C. glabrata. Myricitrin (93.89%; w/w; m/z 463.0876), gallic acid (99.9%; w/w; m/z 169.0142), and ellagic acid (94.2%; w/w; m/z 300.9988) were recovered. The polyphenolic fraction (62.67% (w/w) myricitrin) and the ellagic fraction (67.86% (w/w) ellagic acid) showed the best antifungal performance (MIC between 62.50 and 500 µg/mL), suggesting an association between the majority constituents and the antifungal response of E. uniflora derivatives. However, there is a clear dependence on the presence of the complex chemical mixture. In conclusion, chromatographic strategies were effectively employed to recover the major polyphenols from the leaves of the species.
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Antifúngicos , Eugenia , Extractos Vegetales , Hojas de la Planta , Polifenoles , Polifenoles/farmacología , Polifenoles/química , Polifenoles/aislamiento & purificación , Eugenia/química , Hojas de la Planta/química , Antifúngicos/farmacología , Antifúngicos/química , Antifúngicos/aislamiento & purificación , Extractos Vegetales/farmacología , Extractos Vegetales/química , Pruebas de Sensibilidad Microbiana , Candida/efectos de los fármacos , Espectrometría de Masas en Tándem/métodos , Espectrometría de Masa por Ionización de Electrospray/métodos , Cromatografía Líquida de Alta Presión/métodos , Ácido Gálico/farmacología , Ácido Gálico/químicaRESUMEN
BACKGROUND: Extensive antifungal drug use has enhanced fungal resistance, resulting in persistent mycoses. Combining antifungal plant extracts/compounds with these drugs offers good alternatives to increase the activity of both partners, minimize side effects, and overcome drug resistance. In our previous study, Phytolacca tetramera berries extracts demonstrated activity against Candida spp., correlating with the amount of the main constituent phytolaccoside B and its genin, phytolaccagenin. The extracts and phytolaccagenin altered the fungal plasma membrane by binding to ergosterol, whereas phytolaccoside B increased chitin synthase activity. However, the presence of triterpenoid saponins in Phytolacca spp. has been linked to acute toxicity in humans. PURPOSE: This study aimed to evaluate combinations of P. tetramera berries extracts, phytolaccoside B and phytolaccagenin, together with commercial antifungals [amphotericin B, fluconazole, itraconazole, posaconazole, and caspofungin] against Candida albicans and Candida glabrata, to find synergistic effects with multi-target actions, in which the doses of both partners are reduced, and therefore their toxicity. Additionally, we intended to explore their anti-virulence capacity, thereby hindering the development of drug-resistant strains. METHODS: The effects of these combinations were evaluated using both the checkerboard and isobologram methods. Fractional Inhibitory Concentration Index and Dose Reduction Index were calculated to interpret the combination results. To confirm the multi-target effect, studies on mechanisms of action of synergistic mixtures were performed using ergosterol-binding and quantification assays. The ability to inhibit Candida virulence factors, including biofilm formation and eradication from inert surfaces, was also evaluated. Quantification of active markers was performed using a validated UHPLC-ESI-MS method. RESULTS: Eight synergistic combinations of P. tetramera extracts or phytolaccagenin (but not phytolaccoside B) with itraconazole or posaconazole were obtained against C. albicans, including a resistant strain. These mixtures acted by binding to ergosterol, decreasing its whole content, and inhibiting Candida biofilm formation in 96-well microplates and feeding tubes in vitro, but were unable to eradicate preformed biofilms. CONCLUSIONS: This study demonstrated the synergistic and anti-virulence effects of P. tetramera berries extracts and phytolaccagenin with antifungal drugs against Candida spp., providing novel treatment avenues for fungal infections with reduced doses of both natural products and commercial antifungals, thereby mitigating potential human toxicity concerns.
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Antifúngicos , Candida albicans , Sinergismo Farmacológico , Frutas , Pruebas de Sensibilidad Microbiana , Phytolacca , Extractos Vegetales , Antifúngicos/farmacología , Antifúngicos/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Frutas/química , Candida albicans/efectos de los fármacos , Phytolacca/química , Candida glabrata/efectos de los fármacos , Saponinas/farmacología , Candida/efectos de los fármacosRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Candida auris poses a severe global health threat, with many strains resistant to antifungal treatments, complicating therapy. Exploring natural compounds alongside conventional drugs offers promising therapeutic avenues. The antifungal potential of the ethanolic extract from Caryocar brasiliense (Cb-EE), a plant native to the Brazilian cerrado and renowned for its medicinal properties, was investigated against C. auris. AIM OF THE STUDY: The study examined the chemical composition, antifungal activity, mechanisms of action, and in vivo effects of Cb-EE. MATERIALS AND METHODS: Leaves of C. brasiliense were processed to extract ethanolic extract, which was evaluated for phenolic compounds, flavonoids, and tannins. The antifungal capacity was determined through broth microdilution and checkerboard methods, assessing interaction with conventional antifungals. RESULTS: Cb-EE demonstrated fungistatic activity against various Candida species and Cryptococcus neoformans. Synergy with fluconazole and additive effects with other drugs were observed. Cb-EE inhibited C. auris growth, with the combination of fluconazole extending inhibition. Mechanistic studies revealed interference with fungal membranes, confirmed by sorbitol protection assays, cellular permeability tests, and scanning electron microscopy (SEM). Hemocompatibility and in vivo toxicity tests on Tenebrio molitor showed safety. CONCLUSION: Cb-EE, alone or in combination with fluconazole, effectively treated C. auris infections in vitro and in vivo, suggesting its prospective role as an antifungal agent against this emerging pathogen.
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Antifúngicos , Farmacorresistencia Fúngica Múltiple , Pruebas de Sensibilidad Microbiana , Extractos Vegetales , Hojas de la Planta , Antifúngicos/farmacología , Antifúngicos/aislamiento & purificación , Animales , Extractos Vegetales/farmacología , Hojas de la Planta/química , Candida auris/efectos de los fármacos , Candida auris/aislamiento & purificación , Fluconazol/farmacología , Tenebrio , Sinergismo Farmacológico , Brasil , Candida/efectos de los fármacos , Cryptococcus neoformans/efectos de los fármacosRESUMEN
OBJECTIVES: Fungal infections (FI) pose a public health concern and significantly increase mortality rates, especially within Neonatal Intensive Care Units (NICU). Thus, this study aimed to investigate epidemiological indicators, risk factors, and lethality predictors associated with FI in a NICU. METHODS: This study included 1,510 neonates admitted to the NICU of a reference hospital in Brazil between 2015 and 2022. Demographic data, such as sex, birth weight, gestational age, and use of invasive devices were analyzed. RESULTS: Thirty neonates developed invasive FI, totaling 33 episodes and an incidence of 1.2 per 1,000 patient days. Candida albicans was the most frequent species (52.9 %), the bloodstream was the most affected site (78.9 %), and 72.7 % of infections occurred between 2015 and 2018. The lethality rate associated with FI was 33.3 %, and 90 % of deaths occurred within 30 days of diagnosis of infection. Weight < 750 g, prolonged hospital stay, use of parenteral nutrition, and broad-spectrum antimicrobials were independent risk factors for infection occurrence, especially glycopeptides and 4th generation cephalosporins, having a considerable role in the increase in fungal infections. Weight < 750 g was considered a significant predictor of lethality, and C. albicans had the highest lethality rate (40 %). CONCLUSION: These findings highlight the elevated lethality rate associated with these infections, reinforcing the importance of developing strategies to control FI within NICU.
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Unidades de Cuidado Intensivo Neonatal , Humanos , Recién Nacido , Femenino , Brasil/epidemiología , Masculino , Factores de Riesgo , Incidencia , Estudios Retrospectivos , Micosis/mortalidad , Micosis/epidemiología , Tiempo de Internación/estadística & datos numéricos , Edad Gestacional , Peso al NacerRESUMEN
Invasive fungal infections (IFIs) caused by Candida species are an emerging threat globally, given that patients at-risk and antifungal resistance are increasing. Antimicrobial peptides (AMPs) have shown good therapeutic capacity against different multidrug-resistant (MDR) microorganisms. This study evaluated the activity of the synthetic peptide, PNR20, against Candida albicans ATCC 10231 and a MDR Colombian clinical isolate of Candida auris. Perturbation of yeast cell surface was evaluated using scanning electron microscopy. Cell viability of Vero cells was determined to assess peptide toxicity. Additionally, survival, fungal burden, and histopathology of BALB/c mice infected intravenously with each Candida species and treated with PNR20 were analyzed. Morphological alterations were identified in both species, demonstrating the antifungal effect of PNR20. In vitro, Vero cells' viability was not affected by PNR20. All mice infected with either C. albicans or C. auris and treated with PNR20 survived and had a significant reduction in the fungal burden in the kidney compared to the control group. The histopathological analysis in mice infected and treated with PNR20 showed more preserved tissues, without the presence of yeast, compared to the control groups. This work shows that the utilization of PNR20 is a promising therapeutic alternative against disseminated candidiasis.
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Onychomycosis is a nail infection caused by dermatophytes, non-dermatophyte fungi, and yeasts, especially Candida species. The present study evaluated the combinatorial effect of different cultured extracts of Candida parapsilosis and Trichophyton mentagrophytes and Trichophyton rubrum with fluconazole, itraconazole, and terbinafine against clinical isolates of Trichophyton rubrum. In addition, investigation of the action of the extracts on the wall or membrane was performed. Pure and mixed cultures of Candida parapsilosis and dermatophytes were filtered through a 0.2-µm membrane and submitted to liquid-liquid extraction using ethyl acetate. After a checkerboard, trial with drugs was performed to evaluate the synergistic interaction with the extract. The results obtained for the minimum inhibitory concentration (MIC) of extracts against the T. rubrum strain in isolation were 500-8000 µg/mL. The MIC range for fluconazole, itraconazole, and terbinafine were 2-32 µg/mL, 0.25-0.5 µg/mL, 0.03-64 µg/mL, respectively. However, when the extract was combined with drugs, the MIC values decreased: extracts 1.9-1000 µg/mL, fluconazole 0.25-4, itraconazole 0.03-0.06 µg/mL, and terbinafine 0.001-0.02 µg/mL. The MIC values of the extracts in the Roswell Park Memorial Institute 1640 medium (RPMI) supplemented with sorbitol did not change, suggesting any action on the cell wall. However, in the presence of RPMI supplemented with ergosterol, MIC values of the extracts increased by up to 2×, indicating action on the fungal cell membrane. A synergistic action was observed between products and drugs, detecting a decrease in MIC values. There is potential and a new therapeutic perspective for fungal control.
RESUMEN
Species of the genus Candida, characterized as commensals of the human microbiota, are opportunistic pathogens capable of generating various types of infections with high associated costs. Considering the limited pharmacological arsenal and the emergence of antifungal-resistant strains, the repositioning of drugs is a strategy used to search for new therapeutic alternatives, in which minocycline and doxycycline have been evaluated as potential candidates. Thus, the objective was to evaluate the in vitro antifungal activity of two tetracyclines, minocycline and doxycycline, and their possible mechanism of action against fluconazole-resistant strains of Candida spp. The sensitivity test for antimicrobials was performed using the broth microdilution technique, and the pharmacological interaction with fluconazole was also analysed using the checkerboard method. To analyse the possible mechanisms of action, flow cytometry assays were performed. The minimum inhibitory concentration obtained was 4-427 µg ml-1 for minocycline and 128-512 µg ml-1 for doxycycline, and mostly indifferent and additive interactions with fluconazole were observed. These tetracyclines were found to promote cellular alterations that generated death by apoptosis, with concentration-dependent reactive oxygen species production and reduced cell viability. Therefore, minocycline and doxycycline present themselves as promising study molecules against Candida spp.
Asunto(s)
Antifúngicos , Fluconazol , Humanos , Fluconazol/farmacología , Antifúngicos/farmacología , Candida , Minociclina/farmacología , Doxiciclina/farmacología , Antibacterianos/farmacología , Pruebas de Sensibilidad Microbiana , Farmacorresistencia FúngicaRESUMEN
Advances in the knowledge of the pathogenesis of SARS-CoV-2 allowed the survival of COVID-19 patients in intensive care units. However, due to the clinical characteristics of severe patients, they resulted in the appearance of colonization events. Therefore, we speculate that strains of Candida spp. isolated from COVID-19 patients have virulent genetic and phenotypic backgrounds involved in clinical worsening of patients. The aim of this work was to virutype Candida spp. strains isolated from colonized COVID-19 patients, analyze their genomic diversity, and establish clonal dispersion in care areas. The virulent potential of Candida spp. strains isolated from colonized COVID-19 patients was determined through adhesion tests and the search for genes involved with adherence and invasion. Clonal association was done by analysis of intergenic spacer regions. Six species of Candida were involved as colonizing pathogens in COVID-19 patients. The genotype analysis revealed the presence of adherent and invasive backgrounds. The distribution of clones was identified in the COVID-19 care areas, where C. albicans was the predominant species. Evidence shows that Candida spp. have the necessary genetic tools to be able colonize the lungs, and could be a possible causal agent of coinfections in COVID-19 patients. The detection of dispersion of opportunistic pathogens can be unnoticed by classical epidemiology. Epidemiological surveillance against opportunistic fungal pathogens in COVID-19 patients is an immediate need, since the findings presented demonstrate the potential virulence of Candida spp.
RESUMEN
As a new approach, pyrrolo[1,2-a]pyrazines were synthesized through the cyclization of 2-formylpyrrole-based enaminones in the presence of ammonium acetate. The enaminones were prepared with a straightforward method, reacting the corresponding alkyl 2-(2-formyl-1H-pyrrol-1-yl)acetates, 2-(2-formyl-1H-pyrrol-1-yl)acetonitrile, and 2-(2-formyl-1H-pyrrol-1-yl)acetophenones with DMFDMA. Analogous enaminones elaborated from alkyl (E)-3-(1H-pyrrol-2-yl)acrylates were treated with a Lewis acid to afford indolizines. The antifungal activity of the series of substituted pyrroles, pyrrole-based enaminones, pyrrolo[1,2-a]pyrazines, and indolizines was evaluated on six Candida spp., including two multidrug-resistant ones. Compared to the reference drugs, most test compounds produced a more robust antifungal effect. Docking analysis suggests that the inhibition of yeast growth was probably mediated by the interaction of the compounds with the catalytic site of HMGR of the Candida species.