Clinical characteristics, epidemiology, and mortality of patients receiving antifungal therapy at a university hospital of the Triângulo Mineiro, Brazil / Aspectos clínicos, epidemiológicos e mortalidade de pacientes em uso de terapia antifúngica em um hospital universitário do Triângulo Mineiro, Brasil / Aspectos clínicos, epidemiológicos y mortalidad de pacientes en uso de terapia antifúngica en un hospital universitario del Triângulo Mineiro, BrasiL

Background and Objectives: Invasive fungal infections are associated with high morbidity and mortality in patients admitted to hospital, including those receiving appropriate therapy. The aim of this study was to evaluate the use of prophylactic and preemptive antifungal therapy; clinical and epidemiological features; and mortality of patients admitted to an infectious disease ward of a public high complexity hospital in Uberlandia, Minas Gerais, Brazil. Methods: This is a retrospective study carried out in the infectious diseases ward of a public university hospital in Brazil. Data from patients hospitalized in 2019 and 2020 who received azole antifungals (fluconazole, itraconazole, or voriconazole), echinocandin (anidulafungin), and polyene (amphotericin B) were collected from medical records. Results: During the study period, 111 patients received one or more antifungal agent. The length of hospital stays of patients (29.35 days; p=0.0252), mean number of days of antibacterial drug use (23.5 days; p=0.0164), a diagnosis of AIDS (p=0.0397), mechanical ventilation (MV) (p<0.001), and presence of a nasoenteral tube (p<0.01) were variables that were associated with death. Fungal infection was confirmed in 79 (71.2%) patients who used antifungal drugs. The most frequent fungi isolated were Candida spp. (36; 32.4%) and Cryptococcus spp. (22; 19.8%), and there was an association between infection with these fungi and mortality (p<0.05; OR: 7.61 and 5.53, respectively). Regarding antifungal therapy indication, 56 (50.4%) patients received it as empirical therapy, 33 (29.7%) as targeted therapy, and 22 (19.8%) as preemptive therapy. Conclusion: The factors that contributed to mortality of the patients were longer hospital stays, AIDS, antibacterial medication use, mechanical ventilation, and presence of a nasoenteral tube. The type of antifungal therapy used did not influence the mortality in these patients.(AU)

Justificativa e Objetivos: As infecções fúngicas invasivas apresentam alta morbimortalidade para pacientes hospitalizados, inclusive para aqueles em uso de terapia apropriada. O objetivo foi avaliar a terapia antifúngica profilática e preemptiva, as características clínicas e epidemiológicas, e a mortalidade de pacientes internados em uma enfermaria de doenças infecciosas de um hospital público de alta complexidade de Uberlândia, Minas Gerais, Brasil. Métodos: Trata-se de estudo retrospectivo realizado em uma enfermaria de doenças infecciosas. Os dados coletados dos prontuários foram referentes aos pacientes internados nos anos de 2019 e 2020 e que fizeram uso de antifúngicos azólicos (fluconazol, itraconazol ou voriconazol), equinocandinas (anidulafungina) e poliênicos (anfotericina B). Resultados: Durante o período, 111 pacientes usaram um ou mais antifúngicos. O tempo de internação (29,35 dias, p= 0,0252), média de dias de uso de antibacterianos (23,5 dias; p=0,0164), aids (p=0,0397), uso de ventilação mecânica (VM; p <0,001) e uso de sonda nasoenteral (p<0,01) foram variáveis que se relacionaram com desfecho morte. A infecção por fungos foi confirmada em cultura para 79 (71,2%) pacientes em terapia antifúngica. Os fungos mais frequentes foram Candida spp. (36; 32,4%) e Cryptococcus spp. (22; 19,8%), mostrando relação da infecção por esses fungos com a mortalidade (p<0,05; OR: 7,61 e 5,53, respectivamente). Quanto à terapia, 56 (50,4%) pacientes estavam em terapia empírica; 33 (29,7%) usaram como terapia alvo; e 22 (19,8%) usavam como terapia preemptiva. Conclusão: A mortalidade foi mais frequente entre os pacientes com maior tempo de hospitalização, que tinham aids e que fizeram uso de antibióticos, de ventilação mecânica e de sonda nasoenteral em algum momento da internação. O tipo de terapia antifúngica não influenciou a mortalidade desses pacientes.(AU)

Justificación y Objetivos: Las infecciones fúngicas invasivas presentan una alta morbilidad y mortalidad en los pacientes hospitalizados, incluidos aquellos que utilizan la terapia adecuada. El objetivo fue evaluar la terapia antimicótica profiláctica y preventiva, las características clínicas, epidemiológicas y la mortalidad de pacientes ingresados en una sala de enfermedades infecciosas de un hospital público de alta complejidad en Uberlândia, Minas Gerais, Brasil. Métodos: Este es un estudio retrospectivo realizado en la sala de enfermedades infecciosas de un hospital universitario público en Brasil. Los datos recogidos de las historias clínicas se referían a pacientes hospitalizados en 2019 y 2020 y que utilizaban antifúngicos azoles (fluconazol, itraconazol o voriconazol), equinocandinas (anidulafungina) y polienos (anfotericina B). Resultados: Durante el período, 111 pacientes usaron uno o más antifúngicos. El tiempo de estancia hospitalaria (29,35 días, p= 0,0252), promedio de días de uso de antibacteriano (23,5 días; p=0,0164), SIDA (p=0,0397), uso de ventilación mecánica (VM; p<0,001) y uso de sonda nasoenteral (p<0,01) fueron variables que se relacionaron con el desenlace de muerte. La infección por hongos se confirmó en cultivo en 79 (71,2%) pacientes que usaban medicamentos antimicóticos. Los agentes fúngicos más frecuentes fueron Candida spp. (36; 32,4%) y Cryptococcus spp. (22; 19,8%), mostrando relación entre la infección por estos hongos y la mortalidad (p<0,05; 7,61 y 5,53, respectivamente). En cuanto a la terapia, 56 (50,4%) pacientes estaban en terapia empírica; 33 (29,7%) la utilizaron como terapia diana; y 22 (19,8%) la utilizaron como terapia preventiva. Conclusión: La mortalidad fue más frecuente entre los pacientes con mayor tiempo de internación, que tenían SIDA y que utilizaron antibióticos, ventilación mecánica y sonda nasoenteral en algún momento de la internación. El tipo de terapia antifúngica no influyó en la mortalidad de estos pacientes.(AU)

Systematic review and meta-analysis on synthetic antifungal versus keratolytic agents for topical treatment of Pityriasis Versicolor

Background@#Pityriasis versicolor is a common fungal infection of the superficial skin layer caused by Malassezia furfur, a normal commensal in the skin. Keratolytic agents are popular, cheap, and readily available over-the-counter treatments for pityriasis versicolor. Conventional antifungal agents are more expensive, requiring prescription, and may induce resistant strains. However, evidence of their comparative safety and efficacy is still lacking. @*Objectives@#To assess the efficacy and safety of synthetic antifungals compared to keratolytic agents in the topical treatment of pityriasis versicolor through a systematic review.@*Methods@#We searched the following databases: MEDLINE (from 1966) through PubMed, CENTRAL (Issue 9 of 12, September 2021), EMBASE (from 1974), LILACS (from 1987); Herdin (from 1970), www.clinicaltrials.gov, www. isrctn.com, www.trialregister.nl. We contacted researchers in the field, hand searched relevant conference abstracts, and the Journal of the Philippine Dermatological Society 1992-2019. We included all randomized controlled trials involving patients with diagnosed active pityriasis versicolor where topical antifungal was compared with a topical keratolytic for treatment. Two review authors independently applied eligibility criteria, assessed risk of bias using the Cochrane collaboration tool, and extracted data from included studies. We used RevMan 5.3 to pool dichotomous outcomes using risk ratios (RR) and continuous outcomes using the mean difference (MD), using random-effects meta-analysis. We tested for statistical heterogeneity using both the Chi² test and the I² test. We presented results using forest plots with 95% confidence intervals. We planned to create a funnel plot to determine publication bias but were unable to due to few studies. A Summary of Findings table was created using GRADE profile software for the primary outcomes. @*Results@#We included 8 RCTs with a total of 617 participants that compared azole preparations (ketoconazole, bifonazole and econazole) versus keratolytic agents (selenium sulfide, adapalene, salicylic-benzoic acid). Pooled data showed that azoles did not significantly differ from keratolytic agents for clinical cure (RR 0.99, 0.88, 1.12; 4 RCTs, N=274, I2=55%; very low-quality evidence), and adverse events (0.59 [0.17, 2.06]; very low-quality evidence) based on 6 RCTs (N=536). There were two patients given a keratolytic agent (selenium sulfide shampoo) who had acute dermatitis and discontinued treatment. @*Conclusion@#It is uncertain whether topical azoles are as effective as keratolytic agents in clinical clearance and occurrence of adverse events in patients with pityriasis versicolor. A wider search of grey literature and local studies are warranted. Larger RCTs with low risk of bias are recommended.

Study on the antifungal activity and mechanism of Huangqin decoction against Trichophyton mentagrophytes / 中国药房

OBJECTIVE To study the antifungal activity of Huangqin decoction （HQD） against Trichophyton mentagrophytes and explore its mechanism. METHODS Minimal inhibitory concentration （MIC）， minimal fungicidal concentration （MFC）， mycelial length， spore germination rate， biomass and mycelium ultrastructure observation were performed to evaluate the antifungal activity of HQD against T. mentagrophytes. The effects of HQD on the cell wall of T. mentagrophytes were detected through sorbitol protection experiment. By measuring the content of ergosterol and the activities of squalene epoxide （SE） and lanosterol 14α-demethylase （CYP51）， the activity of HQD on the cell membrane of T. mentagrophytes was investigated. The effects of HQD on T. mentagrophytes mitochondria were investigated by determining the activities of malate dehydrogenase （MDH）， succinate dehydrogenase （SDH）， and ATPases （including sodium potassium ATPase， calcium magnesium ATPase， and total ATPase）. RESULTS HQD exhibited significant antifungal activity against T. mentagrophytes with MIC of 3.13 mg/mL and MFC of 25 mg/mL. After intervention with HQD， the mycelial length of T. mentagrophytes was significantly shortened （P＜0.05）； spore germination rate， biomass， the content of ergosterol in the cell membrane， the activities of SE and CYP51 in the cell membrane and MDH， SDH and ATPase in mitochondria were all decreased significantly （P＜0.05）； cell structure had been ；damaged to a certain extent， but the integrity of the cell wall had not been affected. CONCLUSIONS HQD shows significant antifungal activity against T. mentagrophytes， the mechanism of which may be associated with reducing the 0791- content of ergosterol in the cell membrane and the activities of SE， CYP51， and mitochondria-related enzymes.

Interpretation of China′s fungal infection management policy / 中华实用儿科临床杂志

Fungal infections are a growing public health threat, especially as the at-risk population for invasive fungal disease expanding and antifungal resistance emerging.In 2022, the World Health Organization released the first fungal priority pathogens list, aiming to encourage countries to strengthen the response to fungal infections.As one of the first countries to issue and implement the National Action Plan to Contain Antimicrobial Resistance in the world, China has attached great importance to the management of fungal infections.A series of actions and efforts have been made, including improving the legal and regulatory system related to the prevention and treatment of fungal infections, strengthening the management of clinical application of antifungal drugs, improving the diagnosis and treatment ability of fungal infections and the standardization of diagnosis and treatment, establishing a monitoring and evaluation system for fungal infections and drug resistance.Initial results have been achieved.In the future, under the guidance of the new national action plan to contain antimicrobial resistance, the level of diagnosis and treatment of fungal infections will be further improved to reduce the occurrence of fungal infections and the spread of antifungal resistance.

Clinical treatment and management of invasive fungal disease in recipients of solid organ transplantation / 器官移植

With widespread application of solid organ transplantation (SOT), the incidence of postoperative invasive fungal disease (IFD) in SOT recipients has been increased year by year. In recent years, the awareness of preventive antifungal therapy for SOT recipients has been gradually strengthened. However, the problem of fungal resistance has also emerged, leading to unsatisfactory efficacy of original standardized antifungal regimens. Drug-drug interaction and hepatorenal toxicity induced by drugs are also challenges facing clinicians. In this article, the characteristics of drug-drug interaction and hepatorenal toxicity among triazole, echinocandin and polyene antifungal drugs and immunosuppressants were reviewed, and postoperative preventive strategies for IFD in different types of SOT recipients and treatment strategies for IFD caused by infection of different pathogens were summarized, aiming to provide reference for physicians in organ transplantation and related disciplines.

Artemisia argyi extract subfraction exerts an antifungal effect against dermatophytes by disrupting mitochondrial morphology and function / 中国天然药物

Artemisia argyi (A. argyi), a plant with a longstanding history as a raw material for traditional medicine and functional diets in Asia, has been used traditionally to bathe and soak feet for its disinfectant and itch-relieving properties. Despite its widespread use, scientific evidence validating the antifungal efficacy of A. argyi water extract (AAWE) against dermatophytes, particularly Trichophyton rubrum, Trichophyton mentagrophytes, and Microsporum gypseum, remains limited. This study aimed to substantiate the scientific basis of the folkloric use of A. argyi by evaluating the antifungal effects and the underlying molecular mechanisms of its active subfraction against dermatophytes. The results indicated that AAWE exhibited excellent antifungal effects against the three aforementioned dermatophyte species. The subfraction AAWE6, isolated using D101 macroporous resin, emerged as the most potent subfraction. The minimum inhibitory concentrations (MICs) of AAWE6 against T. rubrum, M. gypseum, and T. mentagrophytes were 312.5, 312.5, and 625 μg·mL-1, respectively. Transmission electron microscopy (TEM) results and assays of enzymes linked to cell wall integrity and cell membrane function indicated that AAWE6 could penetrate the external protective barrier of T. rubrum, creating breaches ("small holes"), and disrupt the internal mitochondrial structure ("granary"). Furthermore, transcriptome data, quantitative real-time PCR (RT-qPCR), and biochemical assays corroborated the severe disruption of mitochondrial function, evidenced by inhibited tricarboxylic acid (TCA) cycle and energy metabolism. Additionally, chemical characterization and molecular docking analyses identified flavonoids, primarily eupatilin (131.16 ± 4.52 mg·g-1) and jaceosidin (4.17 ± 0.18 mg·g-1), as the active components of AAWE6. In conclusion, the subfraction AAWE6 from A. argyi exerts antifungal effects against dermatophytes by disrupting mitochondrial morphology and function. This research validates the traditional use of A. argyi and provides scientific support for its anti-dermatophytic applications, as recognized in the Chinese patent (No. ZL202111161301.9).

Antifungal activity of 2-chloro-N-phenylacetamide: a new molecule with fungicidal and antibiofilm activity against fluconazole-resistant Candida spp / Atividade antifúngica de 2-cloro-N-fenilacetamida: uma nova molécula com atividade fungicida e anti-biofilme contra Candida spp. resistentes a fluconazol

In the current context of emerging drug-resistant fungal pathogens such as Candida albicans and Candida parapsilosis, discovery of new antifungal agents is an urgent matter. This research aimed to evaluate the antifungal potential of 2-chloro-N-phenylacetamide against fluconazole-resistant clinical strains of C. albicans and C. parapsilosis. The antifungal activity of 2-chloro-N-phenylacetamide was evaluated in vitro by the determination of the minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), inhibition of biofilm formation and its rupture, sorbitol and ergosterol assays, and association between this molecule and common antifungal drugs, amphotericin B and fluconazole. The test product inhibited all strains of C. albicans and C. parapsilosis, with a MIC ranging from 128 to 256 µg.mL-1, and a MFC of 512-1,024 µg.mL-1. It also inhibited up to 92% of biofilm formation and rupture of up to 87% of preformed biofilm. 2-chloro-N-phenylacetamide did not promote antifungal activity through binding to cellular membrane ergosterol nor it damages the fungal cell wall. Antagonism was observed when combining this substance with amphotericin B and fluconazole. The substance exhibited significant antifungal activity by inhibiting both planktonic cells and biofilm of fluconazole-resistant strains. Its combination with other antifungals should be avoided and its mechanism of action remains to be established.

No atual contexto de patógenos fúngicos resistentes emergentes tais como Candida albicans e Candida parapsilosis, a descoberta de novos agentes antifúngicos é uma questão urgente. Esta pesquisa teve como objetivo avaliar o potencial antifúngico da 2-cloro-N-fenilacetamida contra cepas clínicas de C. albicans e C. parapsilosis resistentes a fluconazol. A atividade antifúngica da substância foi avaliada in vitro através da determinação da concentração inibitória mínima (CIM), concentração fungicida mínima (CFM), ruptura e inibição da formação de biofilme, ensaios de sorbitol e ergosterol, e associação entre esta molécula e antifúngicos comuns, anfotericina B e fluconazol. O produto teste inibiu todas as cepas de C. albicans e C. parapsilosis, com uma CIM variando de 128 a 256 µg.mL-1, e uma CFM de 512-1,024 µg.mL-1. Também inibiu até 92% da formação de biofilme e causou a ruptura de até 87% de biofilme pré-formado. A 2-cloro-N-fenilacetamida não promoveu atividade antifúngica pela ligação ao ergosterol da membrana celular fúngica, tampouco danificou a parede celular. Antagonismo foi observado ao combinar esta substância com anfotericina B e fluconazol. A substância exibiu atividade antifúngica significativa ao inibir tanto as células planctônicas quanto o biofilme das cepas resistentes ao fluconazol. Sua combinação com outros antifúngicos deve ser evitada e seu mecanismo de ação deve ser estabelecido.

Antifungal activity of 2-chloro-N-phenylacetamide: a new molecule with fungicidal and antibiofilm activity against fluconazole-resistant Candida spp

Abstract In the current context of emerging drug-resistant fungal pathogens such as Candida albicans and Candida parapsilosis, discovery of new antifungal agents is an urgent matter. This research aimed to evaluate the antifungal potential of 2-chloro-N-phenylacetamide against fluconazole-resistant clinical strains of C. albicans and C. parapsilosis. The antifungal activity of 2-chloro-N-phenylacetamide was evaluated in vitro by the determination of the minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), inhibition of biofilm formation and its rupture, sorbitol and ergosterol assays, and association between this molecule and common antifungal drugs, amphotericin B and fluconazole. The test product inhibited all strains of C. albicans and C. parapsilosis, with a MIC ranging from 128 to 256 µg.mL-1, and a MFC of 512-1,024 µg.mL-1. It also inhibited up to 92% of biofilm formation and rupture of up to 87% of preformed biofilm. 2-chloro-N-phenylacetamide did not promote antifungal activity through binding to cellular membrane ergosterol nor it damages the fungal cell wall. Antagonism was observed when combining this substance with amphotericin B and fluconazole. The substance exhibited significant antifungal activity by inhibiting both planktonic cells and biofilm of fluconazole-resistant strains. Its combination with other antifungals should be avoided and its mechanism of action remains to be established.

Resumo No atual contexto de patógenos fúngicos resistentes emergentes tais como Candida albicans e Candida parapsilosis, a descoberta de novos agentes antifúngicos é uma questão urgente. Esta pesquisa teve como objetivo avaliar o potencial antifúngico da 2-cloro-N-fenilacetamida contra cepas clínicas de C. albicans e C. parapsilosis resistentes a fluconazol. A atividade antifúngica da substância foi avaliada in vitro através da determinação da concentração inibitória mínima (CIM), concentração fungicida mínima (CFM), ruptura e inibição da formação de biofilme, ensaios de sorbitol e ergosterol, e associação entre esta molécula e antifúngicos comuns, anfotericina B e fluconazol. O produto teste inibiu todas as cepas de C. albicans e C. parapsilosis, com uma CIM variando de 128 a 256 µg.mL-1, e uma CFM de 512-1,024 µg.mL-1. Também inibiu até 92% da formação de biofilme e causou a ruptura de até 87% de biofilme pré-formado. A 2-cloro-N-fenilacetamida não promoveu atividade antifúngica pela ligação ao ergosterol da membrana celular fúngica, tampouco danificou a parede celular. Antagonismo foi observado ao combinar esta substância com anfotericina B e fluconazol. A substância exibiu atividade antifúngica significativa ao inibir tanto as células planctônicas quanto o biofilme das cepas resistentes ao fluconazol. Sua combinação com outros antifúngicos deve ser evitada e seu mecanismo de ação deve ser estabelecido.

Própolis vermelha e ação antifúngica: potencialidades e desafios / Red própolis and antifungal activity: potentialities and challenges / Propóleo rojo y acción antifúngica: potencialidades y desafíos

Introdução: a própolis é uma composição resinosa produzida por abelhas e utilizada em suas colmeias contra microrganismos. Existem diversos tipos desse composto, sendo o de coloração vermelha o último espécime relatado na literatura. Assim, dentre suas aplicabilidades, a atividade antifúngica da própolis vermelha tem sido explorada com vistas a ampliar sua ação terapêutica. Objetivo: explorar estudos acerca da ação antifúngica da própolis vermelha, identificando suas potencialidades e desafios. Metodologia: foi realizada uma revisão integrativa nas bases de dados bibliográficos MEDLINE (via PubMed), SciELO e Google Acadêmico, complementada por uma diligência nas bases de ensaios clínicos ReBEC e Clinical Trials. Em seguida todos os estudos selecionados foram explorados para obtenção do cenário atual sobre o tema. Resultados: foram incluídos 08 estudos, sendo 01 deles um ensaio clínico. Os estudos comprovam a ação antifúngica da própolis vermelha, principalmente contra Candida spp. e Paracoccidioides brasiliensis, e evidenciam a maior potência fungicida deste composto em detrimento de outros tipos de própolis. Conclusão: a ação antifúngica da própolis vermelha mostra-se uma potencialidade em diversos estudos. Entretanto, o volume de pesquisas científicas relativas a esse tema é insuficiente e a complexidade desse composto configura-se como um desafio à sua aplicabilidade.

Introduction: propolis is a resinous composition produced by compounds and used in their hives against microorganisms. There are several types of this compound, the red one is the last specimen reported in the literature. Thus, among its applicability, the antifungal activity of red propolis has been explored as a path to expand its therapeutic action. Objective: to explore studies about the antifungal action of red propolis, identifying its potentialities and challenges. Methodology: Na integrative review was carried out in the bibliographic databases MEDLINE (via PubMed), SciELO and Google Scholar, complemented by a diligence in ReBEC and Clinical Trials databases. Then, all selected studies were explorers to obtain the current scenario on the subject. Results: 08 studies were included, which 01 of them was a clinical trial. Studies prove the antifungal action of red propolis, mainly against Candida spp. and Paracoccidioides brasiliensis, and show the greater fungicidal power of this compound compared to other types of propolis. Conclusion: the antifungal action of red propolis shows potential in several studies. However, the volume of scientific research on this theme is insufficient and the complexity of this compound represents a challenge to its applicability.

Introducción: el propóleo es una composición resinosa producida por las abejas y utilizada en sus colmenas contra los microorganismos. Existen varios tipos de este compuesto, siendo el rojo el último ejemplar reportado en la literatura. Así, entre sus posibilidades de aplicación, se ha explorado la actividad antifúngica del propóleo rojo con vistas a ampliar su acción terapéutica. Objetivo: explorar estudios sobre la acción antifúngica del propóleo rojo, identificando sus potencialidades y desafíos. Metodología: Se realizó una revisión en las bases de datos bibliográficas MEDLINE (vía PubMed), SciELO y Google Scholar, complementada con una diligencia en las bases de datos de ensayos clínicos ReBEC y Clinical Trials. Luego se exploraron todos los estudios seleccionados para obtener el escenario actual sobre el tema. Resultados: Se incluyeron 08 estudios, 01 de los cuales fue un ensayo clínico. Los estudios demuestran la acción antifúngica del propóleo rojo, principalmente contra Candida spp. y Paracoccidioides brasiliensis, y muestran el mayor poder fungicida de este compuesto en detrimento de otros tipos de propóleos. Conclusión: la acción antifúngica del propóleo rojo muestra potencial en varios estudios. Sin embargo, el volumen de investigación científica sobre este tema es insuficiente y la complejidad de este compuesto representa un desafío para su aplicabilidad.

Efeito de extratos vegetais de Hamamelis virginiana, Persea americana, Cynara scolymus L e Stryphnodendron barbatiman Msobre a expressão fenotípica dos fatores de virulência em biofilmes de Candida albicans / Effect of Hamamelis virginiana, Persea americana, Cynara scolymus L and Stryphnodendron barbatiman M plant extracts on the phenotypic expression of virulence factors in biofilms of the Candida albicans

Objetivo: Analisar a expressão fenotípica de fatores de virulência em biofilmes de Candida albicans frente a extratos glicólicos de plantas. Material e Métodos: Os biofilmes de Candida albicans (ATCC 18804) obtidos a partir de incubação de 48 horas foram expostos por 5 minutos e 24 horas a diferentes concentrações de extratos glicólicos de Hamamelis virginiana e Persea americana, Cynara scolymus L e Stryphnodendron barbatiman M, a fim de verificar a ação antifúngica da proteinase, fosfolipase e hemolisina. Resultados: Todos os extratos foram eficazes na redução do biofilme. Em contato por 5 minutos. os extratos reduziram 50% do biofilme. Após 24 horas. o extrato de Persea americana apresentou o biofilme em 90%, seguido de Cynara scolymus, que o interrompeu em 85%. Houve mudança na intensidade da proteinase após 5 minutos e 24 horas, com uma atividade enzimática média de 0,69 em comparação com o controle de 0,49. Cynara scolymus foi o extrato com maior concentração média de 100 mg/ml; a intensidade da fosfolipase foi alterada com Stryphnodendron barbatiman sendo mais efetivo em 24 horas em relação ao controle (p< 0,0001). A secreção de hemolisina foi modificada por Hamamelis virginiana (12,5 mg/ml) após 5 minutos de exposição e em 24 horas. todos os extratos foram capazes de causar alterações na secreção. Conclusão: Os extratos testados apresentam potencial antifúngico em biofilmes de Candida albicans, implicando em redução significativa dos fatores de virulência. Assim, estes podem ser indicados como uma ferramenta terapêutica alternativa para reduzir a morbidade dessas infecções, já que em ambos os tempos de exposição investigados, eles foram capazes de reduzir a secreção enzimática do fungo (AU)

Objective: Analyze the phenotypic expression of virulence factors in Candida albicans biofilms against plant glycolicextracts. Material and Methods: The biofilms of Candida albicans (ATCC 18804) obtained from incubation for 48 hours were exposed for 5 minutes and 24 hours to different concentrations of glycolic extracts of Hamamelis virginiana and Persea americana, Cynara scolymus L and Stryphnodendron barbatiman M, in order to verify the antifungal activity of the proteinase, phospholipase and hemolysin. Results: All extracts were effective in reducing biofilm. In contact for 5 minutes. the extracts reduced 50% of the biofilm. After 24 hours, the Persea americanaextract showed the biofilm at 90%, followed by Cynara scolymus, which interrupted it at 85%, There was a change in proteinase intensity after 5 minutes and 24 hours. with an average enzymatic activity of 0.69 compared to the control of 0.49. Cynara scolymus was the extract with the highest mean concentration of 100 mg/ml; the phospholipase intensity was changed with Stryphnodendron barbatiman being more effective in 24 hours compared to the control (p< 0.0001). The hemolysin secretion was modified by Hamamelis virginiana (12.5 mg/ml) after 5 minutes of exposure, and in 24 hours. all extracts were capable to cause changes in secretion. Conclusion: The tested extracts have antifungal potential in Candida albicans biofilms, implying a significant reduction in virulence factors. Thus, these can be indicated as an alternative therapeutic tool to reduce the morbidity of these infections, as in both investigated exposure times. they were able to reduce theenzymatic secretion of the fungus (AU)

Evaluación in vitro de la actividad antifúngica de extractos fluidos de Dichrostachys cinerea L. (marabú) frente a Candida albicans

Introducción: La Dichrostachys cinerea L. (marabú) es una planta que crece en Cuba, de la que se estudian propiedades medicinales. La resistencia de levaduras del género Candida a los antifúngicos sintéticos disponibles en la actualidad es cada vez mayor, por lo que se buscan nuevos compuestos de origen vegetal que puedan ser eficaces en el tratamiento de infecciones causadas por este germen. Objetivo: Evaluar la actividad antifúngica in vitro de Dichrostachys cinerea L. contra una cepa de Candida albicans. Métodos: Se realizó un estudio observacional analítico transversal in vitro para evaluar la actividad antifúngica de extractos fluidos de hojas y de tallos de D. cinerea L mediante el método de macrodilución en caldo y como sustancia de referencia el alcohol. Resultados: A través del proceso se mostró la actividad antifúngica del extracto fluido de tallos de D. cinerea L. al 50 % hasta la dilución 1/32, determinada como la concentración mínima inhibitoria; el extracto fluido de hojas al 30 % no logró inhibir el crecimiento de la cepa de Candida albicans ATCC 10231. Conclusiones: La actividad antifúngica del extracto fluido al 50 % de las hojas de Dichrostachys cinerea L. fue efectiva, no así el preparado farmacéutico al 30 %. Se determinó la concentración mínima inhibitoria del extracto fluido de hojas al 50 % y se demostró que ésta superó a la del alcohol al 50 % en tres diluciones contra la Candida albicans.

Introduction: Dichrostachys cinerea L. (marabou) is a plant that grows in Cuba, medicinal properties of this plant are being studied. The resistance of yeasts of the Candida genus to current available synthetic antifungals is increasingly greater. This is why, new compounds of plant origin are being searched for the effective treatment of infections caused by this germ. Objective: To evaluate the in vitro antifungal activity of Dichrostachys cinerea L against a strain of Candida albicans. Methods: An in vitro a cross-sectional analytic observational study was carried out to evaluate the antifungal activity of fluid extracts of D. cinerea L leaves and stems using the broth macro-dilution method and alcohol as the reference substance. Results: Through the process was shown the antifungal activity of the fluid extract of Dichrostachys cinerea L. stems at 50% up to the 1/32 dilution; it was determined as the minimum inhibitory concentration. The leaves fluid extract at 30% failed to inhibit the growth of the Candida albicans ATCC 10231 strain. Conclusions: The antifungal activity of the fluid extract at 50% of the leaves was effective, but not the pharmaceutical preparation at 30%. The minimum inhibitory concentration of the fluid extract of leaves at 50% was determined and it was shown that it exceeded that of alcohol at 50% in three dilutions against Candida albicans.

Oral candidiasis in liver transplant patients: species identification and antifungal susceptibility profile

ABSTRACT Objective This study aimed to verify oral candidiasis, identify the causative species, and investigate the antifungal susceptibility of yeasts isolated from liver transplant patients. Methods A descriptive analysis of 97 patients who underwent liver transplantation was conducted at a hospital. Two clinical examinations (Collections A and B) of the oral cavity were performed. Oral material was collected from all patients, inoculated in Sabouraud Dextrose Agar, and incubated at 35℃ for 48 hours. Samples were identified by molecular sequencing of the internal trascribed space region of rDNA. Results An antifungal susceptibility test with fluconazole, amphotericin B, and micafungin was performed using the Clinical and Laboratory Standards Institute yeast broth microdilution method. Among the patients, 15 presented with oral candidiasis: eight in Collection A and seven in Collection B. The primary type of candidiasis was atrophic, followed by pseudomembranous candidiasis. The most prevalent species was Candida albicans (nine), followed by Candida glabrata (three), Candida tropicalis (two), and Candida dubliniensis (one). Regarding susceptibility to fluconazole, of the 15 samples, 11 were susceptible, three were susceptible in a dose-dependent manner, and one was resistant. Conclusion The most commonly identified type of candidiasis was atrophic, with C. albicans and C. glabrata being the most prevalent causative species. One fluconazole-resistant isolate each of C. tropicalis and C. albicans were identified.

Infecciones fúngicas invasoras en niños con cáncer y portadores de aplasia medular severa en nueve hospitales de la red PINDA, Chile. 2016-2020 / Invasive fungal infections in children with cancer and severe aplastic anemia in nine hospitals from PINDA Network, Chile. 2016-2020

INTRODUCCIÓN: La infección fúngica invasora (IFI) es una causa importante de morbilidad y mortalidad en pacientes oncológicos pediátricos y portadores de aplasia medular (AM) severa. OBJETIVO: Describir la epidemiología de la IFI desde el año 2016 al 2020 en niños con cáncer y AM para evaluar la necesidad de profilaxis antifúngica. MÉTODOS: Estudio retrospectivo, multicéntrico, en pacientes pediátricos con cáncer y AM severa. Se incluyeron IFI probables y probadas. RESULTADOS: Se diagnosticaron 57 casos de IFI, mediana de edad 9 años, 70% probadas y 30% probables. Hubo 42% de infecciones por levaduras y 56% por hongos filamentosos. Los sitios de infección más frecuentes fueron pulmón 38%, sangre 36% y rinosinusal 21%. La frecuencia global fue 5,4%; de ellas 21% en AM severa, 10% en leucemia mieloide aguda (LMA), 6,9% en recaída de LMA, 5,4% en recaída de leucemia linfática aguda (LLA), 3,8% en LLA. Las infecciones por hongos filamentosos predominaron en LMA, recaída de LMA. y AM severa. La mortalidad en pacientes con IFI fue de 11%. CONCLUSIÓN: La frecuencia de IFI concuerda con la literatura médica. Recomendamos profilaxis antifúngica contra hongos filamentosos en pacientes con AM severa, LMA y recaída de LMA. Considerar en recaída de LLA de alto riesgo en etapa de inducción.

BACKGROUND: Invasive fungal infections (IFIs) are an important cause of morbidity and mortality in pediatric oncology patients and severe aplastic anemia (SAA). AIM: To describe the epidemiology of IFI from 2016 to 2020 in children with cancer and SAA to assess the indication of antifungal prophylaxis. METHODS: Multicenter, retrospective study of IFIs in pediatric oncology patients and SAA. Probable and proven IFIs were included. RESULTS: Over the 5-year period, 57 IFIs were found, median age 9 years, 70% were proven and 30% were probable. Yeast infections were 42% and mold infections 56%. The most frequent infection sites were lung 38%, blood 36% and rhinosinusal 21%. The total IFI frequency was 5.4%, 21% in SAA, 10% in acute myeloid leukemia (AML), 6.9% in relapsed AML, 5.4% in relapsed acute lymphoblastic leukemia (ALL), 3.8% in ALL. Mold infections were predominant in AML, relapsed AML, and SAA. IFIs mortality was 11%. CONCLUSION: Frequency of IFI was consistent with the literature. We strongly recommend antifungal prophylaxis against mold infections in patients with SAA, AML, and relapsed AML. Would consider in high risk ALL relapse in induction chemotherapy.

Susceptibilidad in vitro a antifúngicos de especies de Cándida / In vitro antifungal susceptibility of Candida spp

Resumen Objetivo. Analizar la susceptibilidad in vitro de aislamientos de Candida spp. provenientes de onicomicosis obtenidos entre 2016 y 2019, para contribuir con el conocimiento sobre la necesidad o no de realizar pruebas de susceptibilidad a los microorganismos aislados antes de prescribir el tratamiento. Métodos. El estudio consistió en identificar 23 aislamientos de Candida spp. utilizando el sistema automatizado Vitek2® (bioMérieux, Francia). Se determinó la susceptibilidad in vitro de estos aislamientos ante dos antifúngicos tópicos (amorolfina y ciclopirox) y dos antifúngicos sistémicos (fluconazol e itraconazol) por el método de microdilución en caldo M27-A3 del Instituto Estándares para el Laboratorio Clínico (CLSI por sus siglas en inglés) de los Estados Unidos de América. Resultados. La mayoría de los aislamientos correspondieron a Candida parapsilosis (34,8 %), seguido por C. albicans (30,3 %), C. guilliermondii (17,4 %), C. tropicalis (8,7 %), C. dubliniensis (4,4 %) y C. krusei (4,4 %). No se encontraron diferencias estadísticamente significativas entre las CIMs de los diferentes antifúngicos y en promedio hubo susceptibilidad para todos los antifúngicos analizados. Sin embargo, para fluconazol se encontró un aislamiento con CIM alta de C. guilliermondii y un aislamiento resistente de C. parapsilosis. Conclusiones. Las directrices internacionales recomiendan pruebas de susceptibilidad para Candida spp. de hemocultivos o tejidos tras infecciones sistémicas. En todas las demás candidiasis se identifica la especie y se revisan sus patrones de susceptibilidad en la literatura. Por lo tanto, es de importancia conocer que aislamientos de onicomicosis de Candida no-albicans, especialmente de C. guilliermondii y C. parapsilosis, presentan una susceptibilidad disminuida a ciertos antifúngicos que se utilizan como tratamiento, por lo que se recomienda realizar pruebas de susceptibilidad en caso de no tener una buena respuesta al tratamiento en casos de onicomicosis por estas levaduras.

Abstract Aim. The purpose of this investigation was to determine the in vitro susceptibility patterns of Candida spp. isolated from onychomycosis, in order to contribute with strategies for optimal clinical laboratory management of patients with onychomycosis infected with these yeasts. Methods . A total of 23 isolates of Candida spp. were identified with the automatized system Vitek®2 (system bioMérieux, France). In vitro susceptibility patterns were evaluated with two topic antifungals (amorolfine and ciclopirox) and two systemic antifungals (fluconazole and itraconazole) using the Clinical Laboratory and Standards Institute (CLSI) broth microdilution M27-A3 guidelines. Results . Most of the isolates were identified as Candida parapsilosis (34,8 %), followed by C. albicans (30,3 %), C. guilliermondii (17,4 %), C. tropicalis (8,7 %), C. dubliniensis (4,4 %) and C. krusei (4,4 %). There were no statistically significant differences among the MICs of the antifungals tested. However, there was one isolate of C. guilliermondii with high MIC for fluconazole and one fluconazole resistant isolate of C. parapsilosis. Conclusions. Susceptibility tests are only recommended internationally for Candida spp. isolated from blood stream or tissue in systemic infections. In every other candidiasis there is only a species identification, while its susceptibility pattern for treatment is reviewed in literature. Therefore, it is important to report that Candida no-albicans isolates from onychomycosis, especially C. guilliermondii and C. parapsilosis, have a reduced susceptibility to some antifungals commonly used for treatment. According to the obtained in vitro results, we recommend performing antifungal susceptibility testing in those cases of onychomycosis caused by Candida spp. no responsive to treatment.

Antifungal drugs prescription pattern in a tertiary care teaching hospital in South India

Background: Fungal infections are a major threat to human health. Immunocompromised patients are more susceptible to fungal infections which may be from superficial to systemic fungal infections. Proper diagnosis and appropriate prescription is essential for management of these fungal infections. Inappropriate use of antifungal agents can lead to antifungal resistance and adverse effects caused by them. Therefore, this study was carried out to understand the prescription pattern of antifungal drugs among patients from various departments such as general medicine, dermatology, obstetrics, and gynaecology at a tertiary care hospital in South India. Aims and Objectives: The objectives of the study are as follows: (i) To understand the Antifungal prescription practices in our hospital and (ii) to improve the rational use of antifungal drugs. Materials and Methods: This was an observational and cross-sectional study. Inpatients and outpatients of age above 18 years attending Government Omandurar Medical College, Chennai, during the study period of 2 months who were prescribed antifungal drugs were included in this study. The prescriptions of 342 patients were collected and data including age, gender, diagnosis, name of the antifungal drugs, route of administration, dosage form, and duration of treatment were reviewed. Out of 342 prescriptions, 92 contained more than one antifungal drugs in their prescriptions. The data collected were analyzed for frequency of antifungal drugs prescription and percentage values calculated. Results: In our study, females (n = 198; 57.95%) were prescribed antifungal drugs more than males. Most of them are out patients from the age group of 31–50 years (n = 159; 46.49%). Dermatology (n = 272; 79.53%) department had the most number of antifungal prescriptions. Tinea corporis (n = 138; 40.35%) was the most common fungal infection to be prescribed. Clotrimazole (n = 115; 27.89%) was the most commonly prescribed antifungal drug followed by Fluconazole (n = 105; 24.19%). Topical route (n = 268; 61.75%) was the most common route of administration of antifungal drugs followed by oral and parental routes, respectively. Conclusion: This study report helped us to analyze the prescribing pattern of antifungal drugs in our tertiary care hospital. This gave an idea to create guidelines for the rational use of antifungal drugs in our institution.

Candida Bloodstream Infection and Antifungal Susceptibility Over Three Years in a Single Center from Medinah, Saudi Arabia

In the healthcare setting, Candida bloodstream infections significantly increase morbidity and mortality. There is little proof that invasive infections in Saudi Arabia are brought on by Candida spp. To identify Candida species that cause bloodstream infections and ascertain the clinical outcome and risk factors for mortality in a Saudi Arabian tertiary hospital. This retrospective analysis covered all instances in which patients hospitalized to Ohud hospital, a tertiary care facility in Madinah, Saudi Arabia, between January 2019 and December 2021, had positive blood cultures for Candida. Anaerobic and aerobic Bactec bottles were inoculated with blood samples and then incubated at 35°C for five days. Identification-YST card kits from VITEK II (BioMerieux, France) for yeast and yeast-like organisms. Testing for antifungal susceptibility was done using AST YS07. A total of 78 patients (71% men, 29% women) were found to have candidemia. Candida albicans (51.3%), Candida parapsilosis (16.7%), and Candida tropicalis (16.7%) were the three Candida spp. that were most frequently isolated. Those with Saudi (51%; P = 0.500), leukopenia (40%; P = 0.001), neutrophilia (92%; P = 0.638), and thrombocytopenia (42%; P = 0.374) had a higher incidence of candidemia. Fluconazole sensitivity in non-albicans Candida species was 39.5%. Nonetheless, caspofungin was effective against all species. This study discovered an epidemiological shift toward more non-albicans Candida spp. in Saudi Arabia as well as a changing pattern in the Candida spp. causing bloodstream infections.

Isolation of Actinomycetes from Arachis hypogaea L. and Gossypium herbaceum L. for Screening Antibacterial and Antifungal Activities

The principal objective of the present study was to check the antimicrobial activity of Actinomycetes isolated from soil samples collected from the fields of Arachis hypogea L. and Gossipium herbaceum L. against different plant pathogenic strains. Various soil samples were isolated from fields located near the Junagadh district, Gujarat, India. Isolation was followed by a serial dilution process which was later plated on Actinomycete Isolation Agar (AIA) media. Potential colonies were subjected to screening, purification, and storage in glycerol stock. Morphological and Biochemical characterization of the isolates was performed. Isolated candidates were subjected to extraction for the production of the antimicrobial compound. The antimicrobial activity of the purified extract of isolates was tested. Total 30 actinomycete isolates were evaluated for antagonistic activity against pathogenic microorganisms. Isolates C-25, C-15, and G-1 showed the best results in the decreasing order of their potency against fungal pathogens, and C-5, C-25, C-14, and C-13 showed the best results in decreasing order of potency against bacterial pathogens. 3 isolates inhibited all 4 test fungi. 10 isolates inhibited 3 test fungi. 11 isolates inhibited 2 test fungi. 6 isolates did not inhibit any test fungi. 4 isolates show potent inhibition. 15 inhibited Macrophomina. C-10 showed a 1 cm inhibition zone & G-1 showed a 0.8 cm zone of inhibition. 12 isolates gave 0.2-0.6 cm zone and 15 isolates gave negative results against Macrophomina. C-10 showed a very potent zone of inhibition of 0.7 cm. 9 isolates showed a 0.1-0.5 cm zone of inhibition. 20 isolates did not show inhibition against Fusarium. 1 isolate C-11(a) gave the 1cm potent zone of inhibition. 15 isolates gave the 0.7-0.2cm inhibition of the growth. 14 isolates gave negative results against Alternaria fungus. From these results, it was concluded that isolates had antibacterial and antifungal activities and could be used in the development of new antibiotics for pharmaceutical or agricultural purposes.

Antifungal effect of Arnica montana and Hamamelis virginiana against Candida species

Objetivo ­ Avaliar a atividade antifúngica dos extratos glicólicos de Arnica montana e Hamamelis virginiana contra cepas de Candida spp. A candidíase é uma infecção fúngica comum, portanto, a pesquisa de novos agentes antifúngicos tem sido um alvo interessante. Várias plantas apresentaram atividades biológicas e, portanto, podem ser fontes promissoras de produtos naturais com atividades an-tifúngicas. Métodos ­ As atividades antifúngicas dos extratos glicólicos foram avaliadas por meio da determinação da concentração inibitória mínima (CIM) de acordo com o protocolo M27-S3 do Clinical and Laboratory Standards Institute (2008). Resultados ­ O ex-trato glicólico de A. montana apresentou a atividade antifúngica mais forte contra C. tropicalis, com concentração inibitória mínima (CIM) de 10% v/v e concentração fungicida mínima (MFC) de 80% v/v, seguido por C. krusei e C. glabrata, com valores de MIC e MFC de 20% v/v. Além disso, avaliamos a toxicidade dos dois extratos glicólicos no modelo Galleria mellonella usando as curvas de sobre-vivência de larvas tratadas com os extratos. Nossos resultados demonstraram que os extratos glicólicos de A. montana e H. virginiana não exibiram toxicidade contra larvas de G. mellonella e demonstraram atividade antifúngica contra espécies de Candida spp. Con-clusão ­ Assim, ambos os extratos são candidatos promissores para o desenvolvimento de novos agentes antifúngicos.

Objective ­ To evaluate the antifungal activity of Arnica montana and Hamamelis virginiana glycolic extracts against Candida strains. Methods ­ The antifungal activities of glycolic extracts were investigated by determination of the minimum inhibitory concentration (MIC) according to protocol M27-S3 of Clinical and Laboratory Standards Institute (2008). Results ­ A. montana glycolic extract showed the strongest antifungal activity against C. tropicalis, with a minimum inhibitory concentration (MIC) of 10% v/v and a minimum fungicidal concentration (MFC) of 80% v/v, then C. krusei and C. glabrata, with MIC and MFC values of 20% v/v. H. virginiana glycolic extract ex-hibited stronger activity against C. albicans and C. tropicalis, with MIC and MFC values of 10% v/v, than against C. glabrata, C. krusei, and C. parapsilosis, with MIC and MFC values of 20% v/v. Moreover, we evaluated the toxicity of the two glycolic extracts in the Galleria mellonella model using the survival curves of larvae treated with the two extracts. Our results demonstrated that the glycolic extracts of A. montana and H. virginiana exhibited no toxicity against G. mellonella larvae and demonstrated antifungal activity against Candida spe-cies. Conclusion ­ Thus, both extracts are promising candidates for the development of novel antifungal agents.

Pharmacological potential of parasitic Angiosperms against microorganisms / Potencial farmacológico de Angiospermas parásitas contra microorganismos

Parasitic habit plants arouse great interest for their extraordinary growth adaptations and produce different secondary metabolites that allow them to survive the extreme conditions in which they develop. This can provide a range of compounds with multiple uses. However, those plants have been poorly explored and there is very little information about their natural compounds, some healing properties attributed to several communities have been scientifically supported. Articles were consulted in databases (Google Scholar, PubMed, Scielo, Science Direct, Scopus) considering the biological activity reported until June 2021. Parasitic plants present mainly antibacterial activity, some species antifungal moderate activity, and to a lesser extent were found reports of antiprotozoal activity. The composition of parasitic plants should continue to be investigated, which could be an alternative to combat various microorganisms that cause diseases, even resistant to traditional medicines.

Las plantas parásitas despiertan gran interés por sus adaptaciones extraordinarias de crecimiento, y producir diversos metabolitos secundarios que les permiten desarrollarse en condiciones extremas, lo que puede brindar un abanico de compuestos con múltiples usos. Sin embargo, estas plantas han sido pobremente exploradas y es muy poca la información que se tiene de sus compuestos naturales, se han soportado científicamente algunas propiedades curativas, atribuidas por diferentes comunidades. Se consultaron artículos en bases de datos (Google Scholar, PubMed, Scielo, Science Direct, Scopus), teniendo en cuenta la actividad biológica reportada hasta agosto de 2019. Las plantas parásitas presentan principalmente actividad antibacteriana, algunas especies con actividad antifúngica moderada, y en menor proporción reportes de actividad antiprotozoaria. Debe continuarse indagando la composición molecular de estas plantas, lo que podría ser una alternativa para combatir diversos microorganismos causantes de enfermedades, incluso aquellos resistentes a los medicamentos tradicionales.

Antifungal stewardship: What we need to know

Antimicrobial stewardship refers to a well-coordinated program which promotes the scientific and rational use of antimicrobials, reduces the chances of drug resistance and improves patient outcomes. A comprehensive English language literature search was done across multiple databases (PubMed, EMBASE, MEDLINE and Cochrane) for the period 1990–2022, revealing a large volume of reports of growing resistance to established antifungal therapies, against a backdrop of irrational and unscientific prescriptions. As a result of this, antifungal stewardship, a new kid on the block, has recently garnered attention. This review article is an attempt to summarise the basic concept of stewardship programs, highlighting the dire need to implement the same in the present situation of antifungal resistance and treatment failure