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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.

RESUMO

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.

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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.

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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.

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The constituents of the hydroethanolic extract ofAzadiractaindicaroot were investigated using ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-QTOOF-MSE). Acute toxicity was evaluated in an experimental animal model. We investigated the antibacterial activities ofA. indicaroots againstSalmonella typhimuriumandStaphylococcus aureusand the antifungal activities against strains ofTrichophyton rubrum, Candida albicansandCandida tropicalis. We identified nine secondary metabolites in the hydroethanolic extract by UPLC-QTOOF-MSE. The extract was highly effective in inhibiting the growth of T. rubrum strains, so it can be effective in combating the dermatophyte tested,but it had no inhibition potential on any bacterial strains orCandidaspecies evaluated. It was possible to infer that the extract had no acute toxicity in relation to the animal model Danio rerio. Therefore, since neem has a high bioactive potential and adapts well to the climate of semiarid regions, growing this species could become a source of income for farmers by its use to produce naturals fungicide and drug, as alternatives to conventional products, which can cause microbiological resistance and/or are toxic to the environment, besides being expensive.

Os constituintes do extrato hidroetanólico da raiz deA. indicaforam investigados por cromatografia líquida de ultra-alta performance acoplada à espectrometria de massas do tipo quadrupolo-tempo de voo (UPLC-QTOOF-MSE). A toxicidade aguda foi avaliada em modelo animal. Investigamos as atividades antibacterianas contra Salmonella typhimuriumeStaphylococcus aureuse as atividades antifúngicas contra cepas deTrichophyton rubrum, Candida albicanseCandida tropicalis. Identificamos nove metabólitos secundários no extrato etanólico por UPLC-QTOOF-MSE. O extrato foi altamente eficaz na inibição do crescimento de cepas de T. rubrum, podendo ser eficaz no combate ao dermatofito avaliado, mas não apresentou potencial de inibição em nenhuma cepa bacteriana ou espécies deCandidaavaliadas. Também foi possível inferir que o extrato não apresentou toxicidade aguda em relação ao modelo animalDanio rerio. Portanto, como o Neem tem alto potencial bioativo e se adapta bem ao clima das regiões semiáridas, o cultivo dessa espécie pode se tornar uma fonte de renda para os agricultores a partir da utilização da planta para produção de fungicida e/ou fármaco naturais como alternativa aos produtos convencionais, que podem causar resistência microbiológica e/ou são tóxicas ao meio ambiente, além de serem caros.

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Terpenoids, also named terpenes or isoprenoids, are a family of natural products found in all living organisms. Many plants produce terpenoids as secondary metabolites, and these make up a large part of essential oils. One of most important characteristic is that the compounds are volatile, have odor and can be used in a variety of applications in different industrial segments and traditional medicine. Brazil has a rich and diverse flora that can be used as a source of research for obtaining new molecules. Within the Brazilian flora, it is worth mentioning the Caatinga as an exclusively Brazilian biome where plants adapt to a specific series of weather conditions and therefore become a great storehouse of the terpenoid compounds to be described herein. Fungal infections have become increasingly common, and a great demand for new agents with low toxicity and side effects has thus emerged. Scientists must search for new molecules exhibiting antifungal activity to develop new drugs. This review aims to analyze scientific data from the principal published studies describing the use of terpenes and their biological applications as antifungals.

Os terpenóides, também chamados terpenos ou isoprenóides, são uma família de produtos naturais encontrados em todos os organismos vivos. Muitas plantas são produtoras destes metabolitos secundários, que constituem uma grande parte dos óleos essenciais. Uma das características mais importantes é que os compostos são voláteis, têm odor e podem ser utilizados numa variedade de aplicações em diferentes segmentos industriais ou na medicina tradicional. O Brasil tem uma flora rica e diversificada que pode ser utilizada como fonte de pesquisa para a obtenção de novas moléculas. Dentro desta flora, vale a pena mencionar a Caatinga como um bioma exclusivamente brasileiro que possui plantas adaptadas a uma série de condições climáticas e, portanto, um armazém de compostos a serem descritos. As infecções fúngicas são doenças cada vez mais comuns, devido a isso existe uma grande procura de novos agentes com baixa toxicidade e efeitos secundários. Os cientistas devem procurar novas moléculas que exibam atividade antifúngica para o desenvolvimento de novos medicamentos contra as infecções fúngicas. Esta revisão visa analisar dados científicos dos principais estudos publicados que descrevem o uso de terpenóides e as suas aplicações biológicas como antifúngicos.

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ABSTRACT: The constituents of the hydroethanolic extract ofAzadiractaindicaroot were investigated using ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-QTOOF-MSE). Acute toxicity was evaluated in an experimental animal model. We investigated the antibacterial activities ofA. indicaroots againstSalmonella typhimuriumandStaphylococcus aureusand the antifungal activities against strains ofTrichophyton rubrum, Candida albicansandCandida tropicalis. We identified nine secondary metabolites in the hydroethanolic extract by UPLC-QTOOF-MSE. The extract was highly effective in inhibiting the growth of T. rubrum strains, so it can be effective in combating the dermatophyte tested,but it had no inhibition potential on any bacterial strains orCandidaspecies evaluated. It was possible to infer that the extract had no acute toxicity in relation to the animal model Danio rerio. Therefore, since neem has a high bioactive potential and adapts well to the climate of semiarid regions, growing this species could become a source of income for farmers by its use to produce naturals fungicide and drug, as alternatives to conventional products, which can cause microbiological resistance and/or are toxic to the environment, besides being expensive.

RESUMO: Os constituintes do extrato hidroetanólico da raiz deA. indicaforam investigados por cromatografia líquida de ultra-alta performance acoplada à espectrometria de massas do tipo quadrupolo-tempo de voo (UPLC-QTOOF-MSE). A toxicidade aguda foi avaliada em modelo animal. Investigamos as atividades antibacterianas contra Salmonella typhimuriumeStaphylococcus aureuse as atividades antifúngicas contra cepas deTrichophyton rubrum, Candida albicanseCandida tropicalis. Identificamos nove metabólitos secundários no extrato etanólico por UPLC-QTOOF-MSE. O extrato foi altamente eficaz na inibição do crescimento de cepas de T. rubrum, podendo ser eficaz no combate ao dermatofito avaliado, mas não apresentou potencial de inibição em nenhuma cepa bacteriana ou espécies deCandidaavaliadas. Também foi possível inferir que o extrato não apresentou toxicidade aguda em relação ao modelo animalDanio rerio. Portanto, como o Neem tem alto potencial bioativo e se adapta bem ao clima das regiões semiáridas, o cultivo dessa espécie pode se tornar uma fonte de renda para os agricultores a partir da utilização da planta para produção de fungicida e/ou fármaco naturais como alternativa aos produtos convencionais, que podem causar resistência microbiológica e/ou são tóxicas ao meio ambiente, além de serem caros.

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Introduction: Bacillus species are used as biological controllers for phytopathogenic fungi, and the mechanisms to produce controllers include biosynthesis of lipopeptide biosurfactants with antifungal activity. Objective: To evaluate the antifungal potential of the biosurfactants produced by Bacillus strains, selected by molecular screening, on Fusarium oxysporum. Methods: We selected four molecular markers, related to the biosynthesis of surfactin, fengicin, and lichenysin (srfA, spf, fenB, LichAA) in nine Bacillus strains. We used two mineral media with several culture conditions, for biosurfactant production, and a well diffusion test for antifungal potential. Results: Only the biosurfactant produced by UFAB25 inhibits the mycelial growth of F. oxysporum (44 % ± 13): this biosurfactant was positive for srfA, spf, and fenB genes involved in the synthesis of surfactin and fengicine. Antifungal activity depends on culture conditions and the strain. Conclusions: Genetic markers are useful to detect strains with antifungal potential, facilitating the selection of bio-controllers. The biosurfactant profile is influenced by the strain and by culture conditions.

Introducción: Especies de Bacillus han sido empleadas como controladores biológicos contra hongos fitopatógenos. Entre los mecanismos utilizados se destaca la biosíntesis de biosurfactantes lipopeptídicos con actividad antifúngica. Objetivo: Evaluar el potencial antifúngico de los biosurfactantes producidos por cepas Bacillus nativas, previamente seleccionadas mediante tamizaje molecular, sobre Fusarium oxysporum. Métodos: Se utilizaron cuatro marcadores moleculares, relacionados con la biosíntesis de surfactina, fengicina y liquenisina (srfA, spf, fenB, LichAA) sobre nueve cepas de Bacillus. Se utilizaron dos medios minerales con diferentes condiciones de cultivo para la producción del biosurfactante. Se evaluó el potencial antifúngico de los biosurfactantes mediante la prueba de difusión en pozos. Resultados: Se determinó que solo el biosurfactante producido por UFAB25 actúa como inhibidor del crecimiento micelial de Fusarium oxysporum (43.6 % ± 13), esta cepa es positiva para los genes srfA, spf y fenB, involucrados en la síntesis de surfactina y fengicina. La actividad antifúngica depende de las condiciones de cultivo y la cepa. Conclusiones: Los marcadores genéticos ayudan a detectar cepas con potencial antifúngico, facilitando la selección de biocontroladores. El perfil del biosurfactante está influenciado no solo por la cepa, sino también por las condiciones del cultivo.

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BACKGROUND: The prevalence of pulmonary aspergillosis and the importance of its early diagnosis are recognized. However, non-pulmonary involvement, including the sinuses region, is not frequently reported, and an infection in this area can affect all paranasal sinuses (pansinusopathy), being a rare pathology that affects immunocompromised hosts. Recent studies have highlighted the occurrence of Aspergillus flavus resistant to antifungal therapy. Therefore, a nasal sinus infection by resistant Aspergillus strains in immunocompromised patients may be linked to a high risk of lethality. CASE REPORT: We are reporting a resistant A. flavus infection in an allogeneic hematopoietic stem cell transplant recipient with episodes of febrile neutropenia, and prolonged use of various antibacterial drugs and antifungal prophylaxis. The patient underwent brain magnetic resonance, which showed the presence of pansinusopathy, and presented necrosis in the left nasal region. Direct microscopic examination of a sample taken from the nasal mucosa revealed the presence of septate hyphae and conidiophores resembling those of A. flavus, that species being the identification achieved with MALDI-TOF MS. Antifungigram was performed by microdilution in broth (EUCAST-E.DEF. 9.3.2) and E-test, and resistance to amphotericin B was shown in both tests. The patient died after septic shock and hemorrhage. CONCLUSIONS: Invasive fungal infections due to amphotericin-B resistant A. flavus may lead to the death of the patient due to an ineffective therapeutic management. Therefore, antifungal susceptibility testing are of utmost importance for administering the proper treatment.

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Medicinal plants have long been prescribed in Thailand for centuries. Different constituents of extracts have been used for treating of various infectious diseases. However, there is even less information available regarding the use in fungal skin infection. In order to assess traditional Thai claims about the therapeutic potential, this study is focused on exploring the anti-dermatophyte property of the plants that are currently used as traditional medicines. The potential of four different plant species were selected for investigate in vitro anti-dermatophyte activity. Ethanolic extracts of Chromolaena odorata (L.), Ageratina adenophora (Spreng.), Eclipta prostrate (Linn.), and Acorus calamus (L.). were analysed for their total phenolic content as well as total flavonoid content and were then subjected to test of their anti-dermatophyte properties using agar well diffusion method. Qualitative flavonoids and phenolics analysis of the extracts showed their biologically active constituents. Among the species examined, the result indicated that most of the extracts demonstrated anti-dermatophyte activity. In particular, A. calamus showed the highest efficacy against test organisms. The experiment confirmed the chemical constituents and efficacy of some selected plants and provides a scientific confirmation of the use of Thai plants in traditional medicine for fungal skin infections.

As plantas medicinais são prescritas há muito tempo na Tailândia, há séculos. Diferentes constituintes de extratos têm sido usados para o tratamento de várias doenças infecciosas. No entanto, existem ainda menos informações disponíveis sobre o uso em infecções fúngicas da pele. A fim de avaliar as alegações tradicionais tailandesas sobre o potencial terapêutico, este estudo está focado em explorar a propriedade antidermatófita das plantas que são usadas atualmente como medicamentos tradicionais. O potencial de quatro espécies de plantas diferentes foi selecionado para investigar a atividade antidermatófita in vitro. Extratos etanólicos de Chromolaena odorata (L.), Ageratina adenophora (Spreng.), Eclipta prostrate (Linn.) e Acorus calamus (L.) foram analisados quanto ao seu conteúdo fenólico total, bem como ao conteúdo de flavonoides totais. E então submetidos ao teste de suas propriedades antidermatófitas usando o método de difusão em ágar bem. A análise qualitativa de flavonoides e fenólicos dos extratos mostrou seus constituintes biologicamente ativos. Entre as espécies examinadas, o resultado indicou que a maioria dos extratos demonstrou atividade antidermatófita. Em particular, A. calamus mostrou a maior eficácia contra organismos de teste. O experimento confirmou os constituintes químicos e a eficácia de algumas plantas selecionadas e fornece uma confirmação científica do uso de plantas tailandesas na medicina tradicional para infecções fúngicas da pele.

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Abstract Medicinal plants have long been prescribed in Thailand for centuries. Different constituents of extracts have been used for treating of various infectious diseases. However, there is even less information available regarding the use in fungal skin infection. In order to assess traditional Thai claims about the therapeutic potential, this study is focused on exploring the anti-dermatophyte property of the plants that are currently used as traditional medicines. The potential of four different plant species were selected for investigate in vitro anti-dermatophyte activity. Ethanolic extracts of Chromolaena odorata (L.), Ageratina adenophora (Spreng.), Eclipta prostrate (Linn.), and Acorus calamus (L.). were analysed for their total phenolic content as well as total flavonoid content and were then subjected to test of their anti-dermatophyte properties using agar well diffusion method. Qualitative flavonoids and phenolics analysis of the extracts showed their biologically active constituents. Among the species examined, the result indicated that most of the extracts demonstrated anti-dermatophyte activity. In particular, A. calamus showed the highest efficacy against test organisms. The experiment confirmed the chemical constituents and efficacy of some selected plants and provides a scientific confirmation of the use of Thai plants in traditional medicine for fungal skin infections.

Resumo As plantas medicinais são prescritas há muito tempo na Tailândia, há séculos. Diferentes constituintes de extratos têm sido usados para o tratamento de várias doenças infecciosas. No entanto, existem ainda menos informações disponíveis sobre o uso em infecções fúngicas da pele. A fim de avaliar as alegações tradicionais tailandesas sobre o potencial terapêutico, este estudo está focado em explorar a propriedade antidermatófita das plantas que são usadas atualmente como medicamentos tradicionais. O potencial de quatro espécies de plantas diferentes foi selecionado para investigar a atividade antidermatófita in vitro. Extratos etanólicos de Chromolaena odorata (L.), Ageratina adenophora (Spreng.), Eclipta prostrate (Linn.) e Acorus calamus (L.) foram analisados quanto ao seu conteúdo fenólico total, bem como ao conteúdo de flavonoides totais. E então submetidos ao teste de suas propriedades antidermatófitas usando o método de difusão em ágar bem. A análise qualitativa de flavonoides e fenólicos dos extratos mostrou seus constituintes biologicamente ativos. Entre as espécies examinadas, o resultado indicou que a maioria dos extratos demonstrou atividade antidermatófita. Em particular, A. calamus mostrou a maior eficácia contra organismos de teste. O experimento confirmou os constituintes químicos e a eficácia de algumas plantas selecionadas e fornece uma confirmação científica do uso de plantas tailandesas na medicina tradicional para infecções fúngicas da pele.

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The aim of the current report is to describe a cutaneous candidiasis case affecting a canine individual treated at the University Veterinary Hospital of State University of Maranhão (UEMA), in São Luís City. The patient had three-month history of skin diseases; it had been previously subjected to several treatments based on antibiotics, corticosteroids and antifungal drugs that have failed to show clinical improvements. Dermatological assessment has indicated generalized moist dermatitis, intense skin desquamation, alopecia, pruritus and meliceric crusts along the animal's body, mainly in its dorsal region. Complementary tests, such as skin cytology and microscopy, trichogram, qualitative PCR and serology for canine visceral leishmaniasis, as well as fungal culture and antifungigram were requested based on this scenario. Serology recorded inconclusive results for leishmaniasis, whereas PCR recorded negative results in the presence of the agent's DNA. Cytology, microscopy and trichogram results have evidenced fungal infection in the assessed samples. Moreover, mycological culture and antifungigram resulted in the growth of Candida sp. specimens capable of resisting antifungal agents such as amphotericin B, fluconazole, itraconazole and nystatin. The therapy adopted after candidiasis diagnosis confirmation comprised oral doses of manipulated ketoconazole, in combination to topical therapy with shampoo based on moisturizing formulas associated with Miconazole and Chlorhexidine (at 2%), for four weeks. After 30 days, when the adopted therapy was over, the aforementioned animal presented remission of the previously observed lesions and fully improved condition.

The aim of the current report is to describe a cutaneous candidiasis case affecting a canine individual treated at the University Veterinary Hospital of State University of Maranhão (UEMA), in São Luís City. The patient had three-month history of skin diseases; it had been previously subjected to several treatments based on antibiotics, corticosteroids and antifungal drugs that have failed to show clinical improvements. Dermatological assessment has indicated generalized moist dermatitis, intense skin desquamation, alopecia, pruritus and meliceric crusts along the animal's body, mainly in its dorsal region. Complementary tests, such as skin cytology and microscopy, trichogram, qualitative PCR and serology for canine visceral leishmaniasis, as well as fungal culture and antifungigram were requested based on this scenario. Serology recorded inconclusive results for leishmaniasis, whereas PCR recorded negative results in the presence of the agent's DNA. Cytology, microscopy and trichogram results have evidenced fungal infection in the assessed samples. Moreover, mycological culture and antifungigram resulted in the growth of Candida sp. specimens capable of resisting antifungal agents such as amphotericin B, fluconazole, itraconazole and nystatin. The therapy adopted after candidiasis diagnosis confirmation comprised oral doses of manipulated ketoconazole, in combination to topical therapy with shampoo based on moisturizing formulas associated with Miconazole and Chlorhexidine (at 2%), for four weeks. After 30 days, when the adopted therapy was over, the aforementioned animal presented remission of the previously observed lesions and fully improved condition.

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In this study, we sought to demonstrate the toxicity of different concentrations of ozonated water in zebrafish embryos up to 120 hours postfertilization (hpf ) and their antimicrobial activity advantages. For the test, we placed 40 embryos per treatment in Petri dishes containing 30 ml of solution to be tested. The ozone concentrations used were calculated from an initial concentration of 72 µg/ml using the O&L 1.5 RM ozone generator (Ozone & Life, Brazil). Five serial dilutions 1:1 was performed in egg water to produce the ozone treatments. We also analyzed a treatment with 30 ml of egg water without ozone, with only the addition of methylene blue, and a treatment with 30 ml of egg water without the addition of any antifungal agent. The plates were incubated at 28 ± 1°C, and the embryos were analyzed daily until 120 hpf. The survival rate, incubation period, and possible deformities were analyzed. In addition, egg water microbiological analyses were performed to detect total coliforms and fungi and yeasts. The data were tested for normality, and analysis of variance was performed within Minitab®version 1.8 software. The results showed that there was no significant difference in embryo survival or hatching rate between treatments with different ozone concentrations (p > 0.05), and no embryonic deformities were found under any of the ozone concentrations evaluated. It can be concluded that ozone within the concentrations analyzed is not toxic to zebrafish embryos and has antifungal and antimicrobial action.(AU)

Neste estudo, procuramos demonstrar a toxicidade de diferentes concentrações de água ozonizada em embriões de zebrafish até 120 horas pós-fertilização (hpf ) e suas vantagens na atividade antimicrobiana. Para o teste, colocamos 40 embri-ões por tratamento em placas de Petri contendo 30 ml da solução a ser testada. As concentrações de ozônio utilizadas foram calculadas a partir de uma concentração inicial de 72 µg/ml usando o gerador de ozônio O&L 1,5 RM (Ozone & Life, Brasil). Foram realizadas cinco diluições seriadas 1:1 em Egg Water. Também analisamos um tratamento com 30 ml de Egg Water sem ozônio, apenas com adição de azul de metileno, e um tratamento com 30 ml de Egg Water sem adição de nenhum agente antifúngico. As placas foram incubadas a 28 ± 1°C e os embriões foram analisados diariamente até 120 hpf. A taxa de sobrevi-vência, período de incubação e possíveis deformidades foram analisados. Além disso, foram realizadas análises microbiológicas da Egg Water para detectar coliformes totais, fungos e leveduras. Os dados foram testados quanto à normalidade e a análise de variância foi realizada no software Minitab® versão 1.8. Os resultados mostraram que não houve diferença significativa na sobrevivência de embriões ou taxa de eclosão entre os tratamentos com diferentes concentrações de ozônio (p > 0,05), e não foram encontradas deformidades embrionárias sob nenhuma das concentrações de ozônio avaliadas. Pode-se concluir que o ozônio dentro das concentrações analisadas não é tóxico para embriões de zebrafish e possui ação antifúngica e antimicrobiana.(AU)

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The discovery of new natural additives from agro-industrial waste is considered an important research topic. This study investigated the feasibility of ultrasound-assisted extraction (UAE) of antioxidant compounds from corn stigma (CS) and the effect of independent variables (time and solid-solvent ratio) and their interaction in the extraction of CS. Results indicated that the UAE method increases the antioxidant activity and reduces the extraction time by 67%. Optimized conditions for the simultaneous extraction of antioxidants and polyphenols from CS were obtained using 5 min and a solid-solvent ratio of 0.05 g mL-¹. The CS extract obtained by UAE was characterized by ESI-ToF-MS and 27 phytochemicals were reported. The extract showed promising antifungal and antibacterial activities against 23 of the studied microorganisms. Therefore, the CS extract obtained by the UAE can be used as a source of bioactive and antimicrobial compounds for use as a functional ingredient in the food and pharmaceutical industry.

A descoberta de novos aditivos naturais a partir de resíduos agroindustriais é considerada um importante tópico de pesquisa. Este estudo teve como objetivo investigar a viabilidade da extração assistida por ultrassom (EAU) de compostos antioxidantes do estigma do milho (EM) e o efeito de variáveis independentes (tempo e relação sólido-solvente) e sua interação na extração de EM. Os resultados indicaram que a EUA aumenta a atividade antioxidante e reduz o tempo de extração em 67%. Condições otimizadas para a extração simultânea de antioxidantes e polifenóis do EM foram obtidas com 5 min e uma relação sólido-solvente de 0,05 g mL-¹. O extrato de EM obtido pela EUA foi caracterizado por ESI-ToF-MS e 27 fitoquímicos foram encontrados. O extrato apresentou atividades antifúngicas e antibacterianas promissoras contra 23 dos micro-organismos estudados. Portanto, o extrato de EM obtido pela extração assistida por ultrassom pode ser utilizado como fonte de compostos bioativos e antimicrobianos para uso como ingrediente funcional na indústria alimentícia e farmacêutica.

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Abstract Drawbacks associated with the use of chemical fungicides to control plant pathogenic fungi such as Botrytis cinerea stimulate the need for alternatives. Therefore, the present study was carried out to determine the antifungal potentials of Moringa oleifera extracts against B. cinerea. Phytochemical analysis using qualitative chemical tests revealed the presence of huge amount of crucial phytochemicals compounds like phenolic compounds, alkaloids and saponins in the M. oleifera leaf extract. Antifungal bioassay of the crude extracts indicated better mycelial growth inhibition by methanol leaf extract (99%). The minimum inhibitory concentration (MIC) was 5 mg/ml with 100% spore germination inhibition and minimum fungicidal concentration (MFC) was 10 mg/ml with 98.10% mycelial growth inhibition using broth micro dilution and poisoned food techniques. Gas chromatography-mass spectrometry (GC-MS) analysis led to the identification of 67 volatile chemical compounds in the leaf extract with 6-decenoic acid (Z)- (19.87%) was the predominant compound. Further chemical elucidation of the crude extracts performed by liquid chromatography with tandem mass spectrometry (LC-MS/MS) showed the presence of non-volatile chemical compounds, mostly flavones, flavonoids and phenolic acids (i.e. quercetin and kaempferol). Scanning electron microscopy and transmission electron microscopy analysis showed positive effect of M. oleifera leaf extract on the treated conidia and mycelium of B. cinerea. Findings revealed that irreversible surface and ultra-structural changes with severe detrimental effects on conidia and mycelium morphology compared to control treatment. Overall findings suggested that M. oleifera leaf extract is a promising candidate for biological control of fungal pathogens, thus limiting overdependence on chemical fungicides.

Resumo As desvantagens associadas ao uso de fungicidas químicos para controlar fungos fitopatogênicos, como Botrytis cinerea, estimulam a necessidade de alternativas. Portanto, o presente estudo foi realizado para determinar o potencial antifúngico de extratos de Moringa oleifera contra B. cinerea. A análise fitoquímica usando testes químicos qualitativos revelou a presença de uma grande quantidade de compostos fitoquímicos cruciais, como compostos fenólicos, alcaloides e saponinas no extrato da folha de M. oleifera. O bioensaio antifúngico dos extratos brutos indicou melhor inibição do crescimento micelial pelo extrato de folhas de metanol (99%). A concentração inibitória mínima (MIC) foi de 5 mg/mL com 100% de inibição da germinação de esporos e a concentração fungicida mínima (MFC) foi de 10 mg/mL com 98,10% de inibição do crescimento micelial usando microdiluição em caldo e técnicas de alimentos envenenados. A análise por cromatografia gasosa-espectrometria de massa (GC-MS) levou à identificação de 67 compostos químicos voláteis no extrato da folha, sendo o ácido 6-decenoico (Z) (19,87%) o composto predominante. Elucidação química adicional dos extratos brutos realizada por cromatografia líquida com espectrometria de massa em tandem (LC-MS/MS) mostrou a presença de compostos químicos não voláteis, principalmente flavonas, flavonoides e ácidos fenólicos (ou seja, quercetina e kaempferol). As análises de microscopia eletrônica de varredura e microscopia eletrônica de transmissão mostraram efeito positivo do extrato de folhas de M. oleifera sobre os conídios e micélios tratados de B. cinerea. Os resultados revelaram a superfície irreversível e alterações ultraestruturais com graves efeitos prejudiciais sobre os conídios e a morfologia micelial, em comparação com o tratamento de controle. Os resultados gerais sugeriram que o extrato da folha de M. oleifera é um candidato promissor para o controle biológico de patógenos fúngicos, limitando assim a dependência excessiva de fungicidas químicos.

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Objetivo: realizar uma revisão bibliográfica sobre o potencial antimicrobiano do carveol. É uma revisão integrativa entre os anos de 2010-2020 nas bases de dados BVS, PubMed, SciELO, ScienceDirect e Web of Science. Metodologia: dos 2753 artigos recuperados nas bases de dados, apenas 5 foram selecionados para compor os resultados, sendo os gêneros mais estudados Candida, Staphylococcus e Escherichia. A técnica de microdiluição em caldo foi a metodologia mais utilizada para determinar sua ação. Em termos de MIC, para a maioria das espécies, foram excelentes. Em relação ao teste Time-kill, o carveol teve um excelente desempenho na concentração de 4 x MIC, que mostrou uma redução de UFC de 6 log em 2 horas. Não foram encontrados na literatura estudos sobre a utilização do método Checkboard. Além disso, este composto apresentou boa atividade antibiofilme contra bactérias Staphylococcus aureus. Resultados: o possível mecanismo de ação da atividade antimicrobiana do carveol ocorre por meio dos graves danos causados às membranas citoplasmáticas, o que favorecerá a lise celular. Dessa forma, existem poucos estudos na coleção científica disponível que abordem o assunto, sendo necessária a realização de mais estudos in vitro e in vivo para melhor elucidar sua ação.

SUMMARY Aim: to carry out a bibliographic review on the antimicrobial potential of carveol. It is an integrative review between the years 2010-2020 in the BVS, PubMed, SciELO, Science-Direct and Web of Science databases. Methodology: of the 2753 articles retrieved from the databases, only 5 were selected to compose the results, the most studied genera being Candida, Staphylococcus and Escherichia. The broth microdilution technique was the most widely used methodology to determine its action. In terms of MIC, for most species, they were excellent. Regarding the Time-kill test, carveol had an excellent performance at a concentration of 4 x MIC, which showed a reduction of CFU by 6 log in 2 hours. No studies have been found in the literature on the use of the Checkboard method. Further-more, this compound had good antibiofilm activity against Staphylococcus aureus bacteria. Results: the possible mechanism of action of the antimicrobial activity of carveol occurs through the severe damage caused to the cytoplasmic membranes, which will favor cell lysis. Thus, there are few studies in the available scientific collection that address the subject, so it is necessary to carry out more in vitro and in vivo studies to better elucidate its action.

Objetivo: realizar una revisión bibliográfica sobre el potencial antimicrobiano del carveol. Se trata de una revisión integradora entre los años 2010-2020 en las bases de datos de BVS, PubMed, SciELO, ScienceDirect y Web of Science. Metodología: de los 2753 artículos recuperados de las bases de datos, solo se seleccionaron 5 para componer los resultados, siendo los géneros más estudiados Candida, Staphylococcus y Escherichia. La técnica de microdilución en caldo fue la metodología más utilizada para determinar su acción. En cuanto a CIM, para la mayoría de las especies, fueron excelentes. En cuanto al ensayo Time-kill, el carveol tuvo un excelente desempeño a una concentración de 4 x MIC, que mostró una reducción de UFC en 6 log en 2 horas. No se ha encontrado ningún estudio en la literatura sobre el uso del método Checkboard. Además, este compuesto tenía una buena actividad antibiofilm contra la bacteria Staphylococcus aureus. Resultados: el posible mecanismo de acción de la actividad antimicrobiana del carveol se produce a través del severo daño causado en las membranas citoplasmáticas, lo que favorecerá la lisis celular. Así, son pocos los estudios en la colección científica disponible que abordan el tema, por lo que es necesario realizar más estudios in vitro e in vivo para dilucidar mejor su acción.

RESUMO

Drawbacks associated with the use of chemical fungicides to control plant pathogenic fungi such as Botrytis cinerea stimulate the need for alternatives. Therefore, the present study was carried out to determine the antifungal potentials of Moringa oleifera extracts against B. cinerea. Phytochemical analysis using qualitative chemical tests revealed the presence of huge amount of crucial phytochemicals compounds like phenolic compounds, alkaloids and saponins in the M. oleifera leaf extract. Antifungal bioassay of the crude extracts indicated better mycelial growth inhibition by methanol leaf extract (99%). The minimum inhibitory concentration (MIC) was 5 mg/ml with 100% spore germination inhibition and minimum fungicidal concentration (MFC) was 10 mg/ml with 98.10% mycelial growth inhibition using broth micro dilution and poisoned food techniques. Gas chromatographymass spectrometry (GC-MS) analysis led to the identification of 67 volatile chemical compounds in the leaf extract with 6-decenoic acid (Z)- (19.87%) was the predominant compound. Further chemical elucidation of the crude extracts performed by liquid chromatography with tandem mass spectrometry (LC-MS/MS) showed the presence of non-volatile chemical compounds, mostly flavones, flavonoids and phenolic acids (i.e. quercetin and kaempferol). Scanning electron microscopy and transmission electron microscopy analysis showed positive effect of M. oleifera leaf extract on the treated conidia and mycelium of B. cinerea. Findings revealed that irreversible surface and ultra-structural changes with severe detrimental effects on conidia and mycelium morphology compared to control treatment. Overall findings suggested that M. oleifera leaf extract is a promising candidate for biological control of fungal pathogens, thus limiting overdependence on chemical fungicides.(AU)

As desvantagens associadas ao uso de fungicidas químicos para controlar fungos fitopatogênicos, como Botrytis cinerea, estimulam a necessidade de alternativas. Portanto, o presente estudo foi realizado para determinar o potencial antifúngico de extratos de Moringa oleifera contra B. cinerea. A análise fitoquímica usando testes químicos qualitativos revelou a presença de uma grande quantidade de compostos fitoquímicos cruciais, como compostos fenólicos, alcaloides e saponinas no extrato da folha de M. oleifera. O bioensaio antifúngico dos extratos brutos indicou melhor inibição do crescimento micelial pelo extrato de folhas de metanol (99%). A concentração inibitória mínima (MIC) foi de 5 mg/mL com 100% de inibição da germinação de esporos e a concentração fungicida mínima (MFC) foi de 10 mg/mL com 98,10% de inibição do crescimento micelial usando microdiluição em caldo e técnicas de alimentos envenenados. A análise por cromatografia gasosa-espectrometria de massa (GC-MS) levou à identificação de 67 compostos químicos voláteis no extrato da folha, sendo o ácido 6-decenoico (Z) (19,87%) o composto predominante. Elucidação química adicional dos extratos brutos realizada por cromatografia líquida com espectrometria de massa em tandem (LC-MS/MS) mostrou a presença de compostos químicos não voláteis, principalmente flavonas, flavonoides e ácidos fenólicos (ou seja, quercetina e kaempferol). As análises de microscopia eletrônica de varredura e microscopia eletrônica de transmissão mostraram efeito positivo do extrato de folhas de M. oleifera sobre os conídios e micélios tratados de B. cinerea. Os resultados revelaram a superfície irreversível e alterações ultraestruturais com graves efeitos prejudiciais sobre os conídios e a morfologia micelial, em comparação com o tratamento de controle. Os resultados gerais sugeriram que o extrato da folha de M. oleifera é um candidato promissor para o controle biológico de patógenos fúngicos, limitando assim a dependência excessiva de fungicidas químicos.(AU)

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ABSTRACT The aim of the present study was to analyze the chemical composition ofCurcuma longa,Pimenta dioica,Rosmarinus officinalis, andSyzygiumaromaticumessential oils (EOs) and their antifungal and anti-conidiogenic activity againstFusarium verticillioides. The chemical profile of the EOs was determined by GC/MS. The antifungal and anti-conidiogenic activities were evaluated by the agar dilution method. The tested concentrations were 1000ppm, 500ppm, 250ppm and 125ppm.S. aromaticumEO exhibited the highest antifungal effect, followed byP. dioicaand to a lesser extentC. longa. The major compounds of these EOs were eugenol (88.70% inS. aromaticumand 16.70% inP. dioica), methyl eugenol (53.09% inP. dioica), and α-turmerone (44.70%), β-turmerone (20.67%), and Ar-turmerone (17.27%) inC. longa.Rosmarinus officinalispoorly inhibited fungal growth; however, it was the only EO that inhibited conidial production, with its major components being 1,8-cineole (53.48%), α-pinene (15.65%), and (−)-camphor (9.57%). Our results showed that some compounds are capable of decreasing mycelial growth without affecting sporulation, and vice versa. However, not all the compounds of an EO are responsible for its bioactivity. In the present work, we were able to identify different major compounds or mixtures of major compounds that were responsible for antifungal and anti-conidiogenic effects. Further experiments combining these pure components are necessary in order to achieve a highly bioactive natural formulation against the phytopathogenic fungusF. verticillioides.

RESUMEN El objetivo del presente estudio fue analizar la composición química de los aceites esenciales (AE) deCurcuma longa,Pimenta dioica,RosmarinusofficinalisySyzygiumaromaticum, y su actividad antifúngica y anti-esporuladora contraFusarium verticillioides. La composición de los AE se analizó por CG-EM. La actividad antifúngica y anti-esporuladora se evaluó a través del método de dilución en agar usando las siguientes concentraciones: 1.000, 500, 250 y 125ppm. El AE deS. aromaticumdemostró el mayor efecto antifúngico, seguido del deP. dioicay, en menor medida, delC. longa. Los compuestos principales de estos AE fueron eugenol (88,70% enS. aromaticumy 16,70% enP. dioica), metileugenol (53,09% enP. dioica) y α-turmerona (44,70%), β-turmerona (20,67%) y Ar-turmerona (17,27%) enC. longa. El AE deR. officinalisfue el que menor efecto inhibitorio presentó sobre el crecimiento fúngico, pero fue el único que inhibió la producción de conidias; sus principales componentes fueron 1,8-cineol (53,48%), α-pineno (15,65%) y (−)-alcanfor (9,57%). Nuestros resultados demostraron que algunos compuestos son capaces de disminuir el crecimiento del micelio deF. verticillioidessin afectar la esporulación, y vice versa. Sin embargo, no todos los compuestos de un AE son responsables de su bioactividad. En el presente trabajo, pudimos identificar diferentes compuestos o mezclas de compuestos que fueron responsables de los efectos antifúngicos y anti-esporuladores. Se necesitan nuevos experimentos que evalúen la combinación de estos compuestos puros para lograr una formulación bioactiva y de origen natural para el control deF. verticillioides.

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Resumen Las infecciones fúngicas invasoras (IFI) constituyen una de las principales complicaciones infecciosas en pacientes oncohematológicos y con trasplante de células progenitoras hematopoyéticas (TCPH), ocasionando alta morbimortalidad e incrementando significativamente los costos de atención y la estadía hos pitalaria. La epidemiología de las IFI ha cambiado en las últimas décadas, siendo los hongos filamentosos, particularmente Aspergillus spp., los principales agentes etiológicos. Existen múltiples factores de riesgo para una IFI; pero la neutropenia profunda y prolongada, y la inmunodeficiencia celular severa siguen siendo los más importantes. Por este motivo, la población de mayor riesgo la constituyen los pacientes con leucemias agudas, mielodisplasias y TCPH alogénicos con enfermedad injerto contra huésped (EICH), en tratamiento con corticoides. Numerosos ensayos clínicos aleatorizados y metaanálisis han demostrado que la profilaxis antifúngica primaria (PAF) reduce significativamente la incidencia de IFI, tanto de aquellas causadas por Candida spp. como por Aspergillus spp., la mortalidad relacionada a IFI y la mortalidad global en algunos grupos de pacientes. Asimismo, en enfermos de alto riesgo, en donde se espera una incidencia de IFI elevada, es una estrategia costo-efectiva. Varios antifúngicos han demostrado beneficio clínico y pueden utilizarse como estrategia de PAF en diferentes escenarios, presentando ventajas y desventajas que deben ser tenidas en cuenta al momento de indicar una PAF. Para esto, sociedades científicas nacionales e internacionales, han emitido recomendaciones de indicación de PAF. Se analizan los aspectos relacionados con la eficacia clínica de los diferentes antifúngicos según la población de riesgo, las potenciales desventajas, momento y forma de administración.

Abstract Invasive fungal infections (IFI) are among the main infectious complications in patients with hema tological malignancies and with hematopoietic stem cell transplant (HSCT), causing high morbidity and mortality and significantly increasing the healthcare cost and hospital stay. The epidemiology of IFIs has changed in recent decades, with filamentous fungi, particularly Aspergillus spp., being the main etiological agents. There are multiple risk factors for having an IFI; however, the most important are profound and prolonged neutropenia and severe cellular immunodeficiency. For this reason, the population at greatest risk is made up of patients with acute leukemias, myelodysplasias and allogeneic HSCT with graft-versus-host disease (GVHD) treated with cortico steroids. Numerous randomized clinical trials and meta-analyses have shown that primary antifungal prophylaxis (AFP) significantly reduces the incidence of IFI, particularly those caused by Candida spp. and Aspergillus spp., IFI-related mortality, and overall mortality in some group of patients. Likewise, in high-risk patients, where a high incidence of IFI is expected, it is a cost-effective strategy. Several antifungals have demonstrated clinical benefit. They can be used as a AFP strategy in different settings, presenting advantages and disadvantages that must be taken into account in each case. For this, national and international scientific societies have issued recom mendations for the indication of AFP. Aspects related to the different antifungals' clinical efficacy are analyzed considering the population at risk, the potential disadvantages, timing, and form of administration.

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The aim of the present study was to analyze the chemical composition of Curcuma longa, Pimenta dioica, Rosmarinus officinalis, and Syzygium aromaticum essential oils (EOs) and their antifungal and anti-conidiogenic activity against Fusarium verticillioides. The chemical profile of the EOs was determined by GC/MS. The antifungal and anti-conidiogenic activities were evaluated by the agar dilution method. The tested concentrations were 1000ppm, 500ppm, 250ppm and 125ppm. S. aromaticum EO exhibited the highest antifungal effect, followed by P. dioica and to a lesser extent C. longa. The major compounds of these EOs were eugenol (88.70% in S. aromaticum and 16.70% in P. dioica), methyl eugenol (53.09% in P. dioica), and α-turmerone (44.70%), ß-turmerone (20.67%), and Ar-turmerone (17.27%) in C. longa. Rosmarinus officinalis poorly inhibited fungal growth; however, it was the only EO that inhibited conidial production, with its major components being 1,8-cineole (53.48%), α-pinene (15.65%), and (-)-camphor (9.57%). Our results showed that some compounds are capable of decreasing mycelial growth without affecting sporulation, and vice versa. However, not all the compounds of an EO are responsible for its bioactivity. In the present work, we were able to identify different major compounds or mixtures of major compounds that were responsible for antifungal and anti-conidiogenic effects. Further experiments combining these pure components are necessary in order to achieve a highly bioactive natural formulation against the phytopathogenic fungus F. verticillioides.

Assuntos