Actividad biológica in vitro de los extractos acuosos y alcohólicos de tubérculos andinos

Introducción: La medicina ancestral ha utilizado plantas con cualidades medicinales para prevenir y tratar enfermedades; aun cuando este tipo de investigaciones se han incrementado, son escasos los estudios con tubérculos andinos. Objetivo: Determinar la actividad biológica de extractos acuosos y etanólicos de los tubérculos andinos Tropaeolum tuberosum (mashua) y Ullucus tuberosus (melloco). Métodos: La investigación fue experimental y se desarrolló in vitro. La muestra estuvo constituida por 2 tubérculos andinos utilizados en la medicina ancestral. Se aplicaron técnicas de extracción en medio acuoso y etanólico. Los extractos fueron evaluados para determinar la actividad hemoaglutinante, anticoagulante y antimicrobiana con cepas ATCC. Resultados: Se demostró actividad hemoaglutinante en el extracto acuoso de T. tuberosum sobre eritrocitos A. Todos los extractos acuosos mostraron actividad anticoagulante, Tropaeolum tuberosum inhibió la actividad de la coagulación sanguínea (vía intrínseca) con un TTPa> 300 seg. Tanto los extractos acuosos y etanólicos exhibieron actividad antimicrobiana contra cepas ATCC, Tropaeolum tuberosum inhibió el crecimiento de Staphylococcus aureus 25923 con halos de 17 y 22 mm y Ullucus tuberosus (blanco) con halos de 10 y 30 mm, respectivamente. Los extractos acuosos de Tropaeolum tuberosum y Ullucus tuberosus (rojo) inhibieron el crecimiento de Candida tropicalis 66029 con halos de 27 y 12 mm y respectivamente. Conclusiones: Determinada la actividad biológica, se evidencia que los tubérculos andinos estudiados aglutinan eritrocitos humanos, específicamente eritrocitos del grupo A, así mismo, capacidad de inhibir las proteínas plasmáticas de la coagulación y de inhibir el crecimiento bacteriano y micótico de cepas ATTC.

Introduction: Ancestral medicine has used plants with medicinal qualities to prevent and treat diseases, even though this type of research has increased, studies with Andean tubers are scarce. Objective: To determine the biological activity of aqueous and ethanolic extracts of the Andean tubers Tropaeolum tuberosum (mashua) and Ullucus tuberosus (melloco). Methods: The research was experimental and was developed in vitro. The sample consisted of 2 Andean tubers used in ancestral medicine. Extraction techniques were applied in aqueous and ethanolic medium. The extracts were evaluated for hemagglutinating, anticoagulant and antimicrobial activity with ATCC strains. Results: Hemagglutinating activity was demonstrated in the aqueous extract of T. tuberosum on A erythrocyte. All aqueous extracts showed anticoagulant activity, Tropaeolum tuberosum inhibited blood coagulation activity (intrinsic pathway) with an aPTT>300 sec. Both aqueous and ethanolic extracts exhibited antimicrobial activity against ATCC strains, Tropaeolum tuberosum inhibited the growth of Staphylococcus aureus 25923 with halos of 17 and 22 mm and Ullucus tuberosus (white) with halos of 10 and 30 mm, respectively. The aqueous extracts of Tropaeolum tuberosum and Ullucus tuberosus (red) inhibited the growth of Candida tropicalis 66029 with halos of 27 and 12 mm, respectively. Conclusions: Once the biological activity was determined, it was evident that the Andean tubers studied agglutinated human erythrocytes, specifically group A erythrocytes, as well as the ability to inhibit plasma coagulation proteins and inhibit the bacterial and fungal growth of ATTC strains.

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)

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.

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)

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.

Aspergilosis invasiva: definiciones, diagnóstico y tratamiento / Invasive aspergillosis: definitions, diagnosis, and treatment

Resumen La aspergilosis invasiva (AI) es una enfermedad grave y con alta mortalidad. Existen factores de riesgo y se describen brotes intrahospitalarios relacionados con construcciones. También se des cribe una entidad relacionada con la infección por COVID-19, conocida como aspergilosis pulmonar asociada a COVID-19 (APAC). Es de vital importancia implementar un tratamiento adecuado y precoz, especialmente en pacientes inmunocomprometidos y críticamente enfermos. El diagnóstico se basa en reconocer los factores predisponentes, la clínica, la obtención de imágenes, exámenes directos, cultivos, histopatología y biomarca dores como el galactomanano. La droga de elección es el voriconazol, pero se deben conocer las alternativas terapéuticas dada la creciente presencia de aislamientos resistentes.

Abstract Invasive aspergillosis (IA) is a serious disease with high mortality. There are several risk factors and in-hospital outbreaks related with construction have been described. An entity related to COVID-19 infection, known as COVID-19 associated pulmonary aspergillosis (CAPA), has recently appeared. Early and appropriate treatment is of paramount importance, especially in immunocompromised and critically ill patients. Diagnosis is based on recognition of predisposing factors, clinical signs, imaging, direct examination, culture, histopathology, and biomarkers such as galactomannan. The drug of choice is voriconazole, but alternative therapies must be taken into account given the increasing presence of resistant isolates.

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.

In vitro sensitivity of Malassezia furfur isolates from HIV-positive and negative patients to antifungal agents / Sensibilidad in vitro a antifúngicos de aislamientos de Malassezia furfur de pacientes positivos y negativos para HIV

Introduction. Malassezia is a lipophilic and lipid-dependent yeast genus belonging to the skin microbiota of humans and other animals. However, due to dysbiosis processes or other factors in the host, this yeast can cause different pathologies, ranging from skin diseases, such as seborrheic dermatitis, to fungemia. Isolation of Malassezia furfur has been reported in HIV-positive patients with or without skin lesions. Due to its opportunistic nature and its variable resistance to antifungal compounds, it is relevant to know the Malassezia sensitivity profiles. Objective. To determine the sensitivity to different antifungal agents, of clinical isolates of M. furfur obtained from HIV-positive or negative patients, with or without seborrheic dermatitis. Materials and methods. Assessment of isolates sensitivity to itraconazole, voriconazole, fluconazole, and amphotericin B was performed by two techniques: (1) Broth microdilution using Clinical and Laboratory Standards Institute (CLSI) protocol M27-A3 with modifications; and (2) agar tests using Etest®. Results. Isolates obtained from HIV patients showed an increase in the minimum inhibitory concentration of fluconazole, voriconazole, and amphotericin B, compared with those of non-HIV patients. Itraconazole was the antifungal with the lowest minimum inhibitory concentration (MIC) in most isolates. Conclusion. We observed differences in the sensitivity profiles of M. furfur isolates according to the context of the patient. High MIC of antifungals like fluconazole, commonly used for treating pathologies caused by Malassezia, were identified.

Introducción. Malassezia es un género de levaduras lipofílicas que dependen de los lípidos y hacen parte de la microbiota de la piel de humanos y otros animales. No obstante, debido a procesos de disbiosis u otros factores en el huésped, esta levadura puede llegar a causar diferentes enfermedades: desde cutáneas (como dermatitis seborreica) hasta fungemias. Se han reportado aislamientos de Malassezia furfur en pacientes positivos para HIV, con lesiones cutáneas o sin ellas. Por su carácter oportunista y sensibilidad variable a los compuestos antifúngicos, es relevante conocer los perfiles de sensibilidad. Objetivo. Determinar la sensibilidad a diferentes antifúngicos de aislamientos clínicos de M. furfur obtenidos de pacientes positivos o negativos para HIV, con dermatitis seborreica o sin ella. Materiales y métodos. La sensibilidad de los aislamientos a itraconazol, voriconazol, fluconazol y anfotericina B, se determinó mediante dos técnicas: microdilución en caldo según el protocolo M27-A3 del Clinical & Laboratory Standards Institute (CLSI), con modificaciones, y pruebas en agar mediante Etest®. Resultados. Los aislamientos obtenidos de pacientes con HIV mostraron aumento de la concentración inhibitoria mínima a fluconazol, voriconazol y anfotericina B, en comparación con los de pacientes sin HIV. Por otro lado, al evaluar la mayoría de los aislamientos, el itraconazol fue el antifúngico con la menor concentración inhibitoria mínima. Conclusión. Se evidencian diferencias en los perfiles de sensibilidad de los aislamientos de M. furfur, según el contexto del paciente, y elevadas concentraciones inhibitorias mínimas de antifúngicos como el fluconazol, usados comúnmente para el tratamiento de las enfermedades causadas por Malassezia spp.

Una experiencia de siete años en el laboratorio de Micología del Hospital de Pediatría Juan P. Garrahan / A seven-year experience in the Mycology Laboratory of Hospital de Pediatría Juan P. Garrahan

En noviembre del año 2015 nos incorporamos al Laboratorio de Micología del Servicio de Microbiología del Hospital Garrahan. En este breve resumen queremos compartir los avances logrados a través de nuestra experiencia durante siete años de trabajo profesional. Debido a los diagnósticos realizados y su complejidad, consideramos que el Hospital Garrahan, sus pacientes y la comunidad toda necesitan contar con un laboratorio de Micología que responda a sus necesidades. Creemos haber iniciado un camino que esperamos continúe y culmine con la creación de la Unidad de Micología (AU)

In November 2015 we joined the Mycology Laboratory of the Microbiology Service of the Hospital Garrahan. In this brief summary we want to share the advances achieved through our experience during seven years of professional work. Due to the diagnosis made and their complexity, we believe that the Hospital Garrahan, its patients and the entire community, need to have a Mycology laboratory that responds to their requirements. We believe we have started a path that we hope will continue and culminate with the creation of the Mycology Unit (AU)

Scedosporiosis pulmonar post COVID-19 en paciente diabético: a propósito de un caso

Las especies de Scedosporium son consideradas patógenos oportunistas emergentes, que afectan a pacientes inmunocomprometidos o con respuesta inmunológica normal. La enfermedad invasiva grave supera tasas de mortalidad del 80 %. Se describe caso con afectación pulmonar causada por el complejo de especies de Scedosporium en un paciente masculino de 75 años de edad, procedente de Caracas, Venezuela, con diabetes mellitus tipo 2, infección respiratoria baja, dos infecciones previas por enfermedad por coronavirus 2019 (COVID-19) e imagen radiológica de lesión de ocupación de espacio pulmonar basal izquierdo. Se envió al laboratorio de microbiología porción de aproximadamente 1 cm2 de tejido pulmonar, solicitando estudios micológicos y para micobacterias. Al examen directo con KOH al 20 % se observó un fragmento de hifa hialina tabicada. A los 12 días de incubación hubo crecimiento en agar Sabouraud dextrosa más gentamicina de colonias vellosas con pigmentado difusible color amarillo pálido a mostaza. Se realizó examen directo a las colonias con azul de algodón, observándose estructuras compatibles con el complejo de especies de Scedosporium. Scedosporium spp., es el segundo hongo filamentoso, después de Aspergillus spp., causante de infecciones respiratorias bajas. El paciente fue tratado con voriconazol después del diagnóstico micológico con una evolución satisfactoria. Las infecciones por especies de Scedosporium afectan órganos internos como los pulmones, similar al caso descrito. La infección por COVID-19 es un factor predisponente para adquirir infecciones fúngicas poco frecuentes. El laboratorio de microbiología cumple un rol importante en el diagnóstico de micosis causadas por hongos inusuales.

Scedosporium species are considered emerging opportunistic pathogens affecting immunocompromised patients or patients with normal immune response. Mortality rates exceed 80 % in severe invasive disease. We describe a case of lung involvement caused by Scedosporium species complex in a 75-year-old male patient from Caracas, Venezuela, with type 2 diabetes mellitus, lower respiratory tract infection, two previous coronavirus disease infections 2019 (COVID-19) and radiological findings of a left basal lung space-occupying lesion. A piece of lung tissue measuring approximately one cm2 was sent to the microbiology laboratory, requesting mycology and mycobacteria studies. Direct examination with 20 % KOH revealed a hyaline septate hyphal fragment. Growth of hairy colonies with diffusible pale yellow to mustard pigment was observed on Sabouraud dextrose plus gentamicin agar after 12 days of incubation. Structures compatible with the Scedosporium species complex were observed on direct examination of the colonies with cotton blue. Scedosporium spp. is the second most common filamentous fungus causing infections of the lower respiratory tract after Aspergillus spp. The patient was treated with voriconazole after mycological diagnosis with satisfactory outcome. Infections with Scedosporium spp. affect internal organs such as the lungs, similar to the case described. COVID-19 infection predisposes to the acquisition of uncommon fungal infections. The microbiology laboratory plays an important role in the diagnosis of mycoses caused by unusual fungi.

Avaliação da interação farmacológica de antifúngicos e quimioterápicos: uma revisão sistemática / Evaluation of pharmacological interaction of antifungals and chemotherapy: a systematic review

Objetivo: avaliar, por meio da literatura existente, a interação farmacológica de antifúngicos e quimioterápicos. Métodos: foi realizado um estudo de revisão sistemática de acordo com o diagrama de fluxo do processo de pesquisa PRISMA. Os descritores escolhidos foram: drug interactions, CYP inhibitors, antifungal e antineoplastic, mediante análise realizada no MESH. As bases de dados escolhidas foram: Pubmed, Lilacs e Scielo. O período considerado para busca de artigos publicados foi de 2015 a 2020. Resultados: no banco de dados PubMed, foram encontrados 54 artigos, enquanto, nas bases Lilacs e Scielo, não foram encontrados artigos de acordo com os critérios estabelecidos. Dos 54 artigos, 7 foram selecionados para esta revisão. O intervalo com maior número de publicações foi de 2015-2016. Os antifúngicos mais citados nos resultados foram os inibidores fortes da CYP (Cetoconazol, Itraconazol e Voriconazol). Conclusão: a revisão sistemática da literatura mostrou que não existe uma correlação exata entre a interação farmacológica dos antifúngicos com os antineoplásicos, quando administrados de forma simultânea. São necessários mais estudos atuais que possam monitorar e estabelecer, de forma precisa, a relação dessas interações.

Objective: to evaluate, through the existing literature, the pharmacological interaction of antifungals and chemotherapeutics. Methods: a systematic review study was conducted according to the PRISMA research process flow diagram. The descriptors were chosen by analysis performed in MESH. The descriptors chosen were: drug interactions, CYP inhibitors, antifungal and antineoplastic. The databases chosen were: Pubmed, Lilacs, and Scielo. The period considered for the search of published articles was from 2015 to 2020. Results: in the PubMed database, 54 articles were found, while in the Lilacs and Scielo databases, no articles were found according to the established criteria. Of the 54 articles, 8 were selected for this review. The interval that had the highest number of publications was 2015-2016. The most cited antifungal drugs in the results were the strong CYP inhibitors. Conclusion: the systematic review of the literature showed that there is no exact correlation between the pharmacological interaction of antifungals with antineoplastic drugs when administered simultaneously. More current studies are needed that can accurately monitor and establish the relationship between these interactions.

Análisis fitoquímico preliminar y actividad antifúngica In vitro del extracto etanólico de las hojas de Solanum hispidum pers. Colectadas en la localidad Obraje - Perú / Preliminary phytochemical analysis and in vitro antifungal activity of the ethanolic extract of the leaves of Solanum hispidum pers. collected in the locality in Obraje - Peru

RESUMEN Objetivo . Analizar y determinar la actividad antifúngica in vitro del extracto etanólico de las hojas de Solanum hispidum Pers. Materiales y métodos . Se realizó el análisis fitoquímico preliminar cualitativo mediante reacciones de color y precipitación. Se investigó la actividad antifúngica in vitro frente a Candida albicans, Aspergillus brasilensis y Trichophyton mentagrophytes usando el método de difusión en pozo de agar y el ensayo de la concentración mínima inhibitoria (CMI). Resultados . El análisis fitoquímico preliminar cualitativo mostró la presencia de compuestos fenólicos, taninos, flavonoides, esteroides, alcaloides y saponinas. La actividad antifúngica in vitro fue demostrada para todos cultivos fúngicos con halos de inhibición entre 23 a 26 mm. Los valores de la CMI fueron de 125, 250 y 125 µg/mL para C. albicans, A. brasilensis y T. mentagrophytes, respectivamente. Conclusiones. El extracto etanólico de las hojas de Solanum hispidum Pers contiene importantes metabolitos secundarios y tiene moderada actividad antifúngica.

ABSTRACT Objective. To analyze and determine the in vitro antifungical activity of the ethanolic extract of the leaves of Solanum hispidum Pers. Materials and methods. We carried out a preliminary qualitative phytochemical analysis by color and precipitation reactions. We evaluated the in vitro antifungical activity against Candida albicans, Aspergillus brasilensis and Trichophyton mentagrophytes by using the agar well diffusion method and the minimum inhibitory concentration (MIC) assay. Results. Preliminary qualitative phytochemical analysis showed the presence of phenolic compounds, tannins, flavonoids, steroids, alkaloids and saponins. In vitro antifungal activity was demonstrated for all fungal cultures with inhibition halos between 23 to 26 mm. The MIC values were 125, 250, and 125 μg/mL for C. albicans, A. brasilensis, and T. mentagrophytes, respectively. Conclusions. The ethanolic extract of the leaves of Solanum hispidum Pers. contains important secondary metabolites and has moderate antifungical activity.

Infección fúngica invasiva por Saprochaete capitata en un niño con aplasia medular / Invasive fungal infection by Saprochaete capitata in a child with bone marrow aplasia

RESUMEN Saprochaete capitata es una causa rara de infección fúngica invasiva en pacientes inmunocomprometidos con alta mortalidad y resistencia antifúngica. Presentamos el caso de un niño de cinco años con diagnóstico de aplasia medular, sometido a trasplante de progenitores hematopoyéticos (TPH), que cursó con neutropenia febril persistente, dolor abdominal intenso, aparición de lesiones maculopapulares en piel y deterioro de la función renal. Se identificó la presencia de S. capitata, en hemocultivos transcatéter venoso central. Esta infección fúngica invasiva resulta ser rara, pero emergente y potencialmente mortal, en pacientes con neutropenia febril persistente y uso prolongado de dispositivos invasivos intravasculares como catéter venoso central.

ABSTRACT Saprochaete capitata is a rare cause of invasive fungal infection in immunocompromised patients with high mortality and antifungal resistance. We present the case of a 5-year-old boy with bone marrow aplasia, who underwent hematopoietic stem cell transplantation (HSCT) and presented persistent febrile neutropenia, abdominal pain, appearance of maculopapular lesions on the skin, and impaired renal function. The presence of S. capitata was identified by blood culture from a central venous catheter. This invasive fungal infection is rare but emergent and life-threatening, especially in immunocompromised patients with persistent febrile neutropenia and prolonged use of invasive devices such as central venous catheters.

Antifungals from plants: a bibliometric analysis of the last two decades (2000-2020) / Antifúngicos de plantas: un análisis bibliométrico de las últimas dos décadas (2000-2020)

This study aimed to analyse the world scientific production on antifungals from plants indexed in the Scopus database (2000-2020), highlighting the Cuban scientific production on this topic as a case study. Scopus raw data based on antifungal and plants hits were cleaned using the OpenRefine tool to eliminate similar and duplicate results. Cleaned data was processed using VOSviewer software for keyword-based bibliometric analysis. The 5000 most common words from the Corpus of Contemporary American English were excluded. A co-occurrence analysis was performed taking into account only authors keywords and using the complete count method. 24 084 documents were identified, of which 85.8percent were original articles and 9.6percent were reviews. The most productive journals were Journals of Ethnopharmacology, Natural Product Research and Fitoterapia. The annual scientific production was uniform with a linear growth. The thematic structure according to the co-occurrence network indicates that the most frequent terms were essential oils, antioxidant, medicinal plants, Candida albicans and flavonoids. In the case of Cuba, of the 64 publications on the subject, 90.6percent were original articles and 6.3percent were reviews. The Cuban magazines with the highest production were Revista Cubana de Plantas Medicinales and Biotecnología Aplicada. The most frequent terms according to the co-occurrence network in Cuban publications were Staphylococcus aureus, Candida albicans, plant leaf, antimicrobial activity, medicinal plants and flavonoids. These results prove that the global scientific community as well as the Cuban scientist are interested on the topic, further demonstrating that plants could become a reliable source of antifungal drugs(AU)

El objetivo del presente estudio fue analizar la producción científica mundial sobre antifúngicos de plantas recogida en la base de datos Scopus (2000-2020), con atención a la producción científica cubana como caso/estudio. Los datos resultantes de la búsqueda por coincidencia de las palabras antifungal y plants se filtraron con la herramienta OpenRefine, que eliminó resultados similares y duplicados. Se empleó el programa VOSviewer para el análisis bibliométrico basado en palabras claves, que excluyó las 5000 más comunes del Corpus of Contemporary American English. Se realizó un análisis de coocurrencia que consideró las palabras clave definidas por los autores en cada artículo a través del método de conteo completo. Se identificaron 24 084 documentos, de los cuales un 85,8 por ciento resultaron artículos originales y un 9,6 por ciento, artículos de revisión. Las revistas más productivas fueron Journals of Ethnopharmacology, Natural Product Research y Fitoterapia. La producción científica anual fue uniforme, con un crecimiento lineal. La red de coocurrencia indicó que los términos más frecuentes fueron aceites esenciales, antioxidante, plantas medicinales, Candida albicans y flavonoides. En Cuba, de las 64 publicaciones sobre el tema, el 90,6 por ciento resultaron ser artículos originales y 6,3 por ciento, artículos de revisión. Las revistas cubanas con mayor producción fueron Revista Cubana de Plantas Medicinales y Biotecnología Aplicada. Los términos más frecuentes en las publicaciones cubanas fueron Staphylococcus aureus, Candida albicans, hojas de plantas, actividad antimicrobiana, plantas medicinales y flavonoides. Estos resultados demuestran que, tanto la comunidad científica mundial como la cubana, manifiestan creciente interés en el tema, lo cual evidencia el potencial de las plantas como fuente confiable de medicamentos antifúngicos(AU)

Plant metabolite 5-pentadecyl resorcinol is produced by the Amazonian fungus Penicillium sclerotiorum LM 5679 / O metabólito vegetal 5-pentadecil resorcinol é produzido pelo fungo amazônico Penicillium sclerotiorum LM 5679

Since the classic studies of Alexander Flemming, Penicillium strains have been known as a rich source of antimicrobial substances. Recent studies have identified novel metabolites produced by Penicillium sclerotiorum that have antibacterial, antifouling and pharmaceutical activities. Here, we report the isolation of a P. sclerotiorum (LM 5679) from Amazonian soil and carry out a culture-based study to determine whether it can produce any novel secondary metabolite(s) that are not thus-far reported for this genus. Using a submerged culture system, secondary metabolites were recovered by solvent extract followed by thin-layer chromatography, nuclear magnetic resonance, and mass spectroscopy. One novel secondary metabolite was isolated from P. sclerotiorum (LM 5679); the phenolic compound 5-pentadecyl resorcinol widely known as an antifungal, that is produced by diverse plant species. This metabolite was not reported previously in any Penicillium species and was only found once before in fungi (that time, in a Fusarium). Here, we discuss the known activities of 5-pentadecyl resorcinol in the context of its mode-of-action as a hydrophobic (chaotropicity-mediated) stressor.

Desde os estudos clássicos de Alexander Flemming, as cepas de Penicillium são conhecidas como uma fonte rica em substâncias antimicrobianas. Estudos recentes identificaram novos metabólitos produzidos pela espécie Penicillium sclerotiorum com atividades antibacteriana, anti-incrustante e farmacêutica. Aqui, relatamos o isolamento de uma colônia de P. sclerotiorum (LM 5679) do solo amazônico e relatamos também o estudo baseado em cultura para determinar se ele pode produzir qualquer novo metabólito (s) secundário (s) que não foram relatados até agora para este gênero. Usando um sistema de cultura submerso, os metabólitos secundários foram recuperados por extrato de solvente seguido por cromatografia em camada delgada, ressonância magnética nuclear e espectroscopia de massa. Um novo metabólito secundário foi isolado de P. sclerotiorum (LM 5679); o composto fenólico 5-pentadecil resorcinol que é amplamente conhecido como um antifúngico que é produzido por diversas espécies de plantas. Este metabólito não foi relatado anteriormente em nenhuma espécie de Penicillium, e foi encontrado apenas uma vez em fungos (Fusarium). Aqui, discutimos as atividades conhecidas do 5-pentadecil resorcinol no contexto de seu modo de ação como um estressor hidrofóbico (mediado pela caotropicidade).

Plant metabolite 5-pentadecyl resorcinol is produced by the Amazonian fungus Penicillium sclerotiorum LM 5679

Abstract Since the classic studies of Alexander Flemming, Penicillium strains have been known as a rich source of antimicrobial substances. Recent studies have identified novel metabolites produced by Penicillium sclerotiorum that have antibacterial, antifouling and pharmaceutical activities. Here, we report the isolation of a P. sclerotiorum (LM 5679) from Amazonian soil and carry out a culture-based study to determine whether it can produce any novel secondary metabolite(s) that are not thus-far reported for this genus. Using a submerged culture system, secondary metabolites were recovered by solvent extract followed by thin-layer chromatography, nuclear magnetic resonance, and mass spectroscopy. One novel secondary metabolite was isolated from P. sclerotiorum (LM 5679); the phenolic compound 5-pentadecyl resorcinol widely known as an antifungal, that is produced by diverse plant species. This metabolite was not reported previously in any Penicillium species and was only found once before in fungi (that time, in a Fusarium). Here, we discuss the known activities of 5-pentadecyl resorcinol in the context of its mode-of-action as a hydrophobic (chaotropicity-mediated) stressor.

Resumo Desde os estudos clássicos de Alexander Flemming, as cepas de Penicillium são conhecidas como uma fonte rica em substâncias antimicrobianas. Estudos recentes identificaram novos metabólitos produzidos pela espécie Penicillium sclerotiorum com atividades antibacteriana, anti-incrustante e farmacêutica. Aqui, relatamos o isolamento de uma colônia de P. sclerotiorum (LM 5679) do solo amazônico e relatamos também o estudo baseado em cultura para determinar se ele pode produzir qualquer novo metabólito (s) secundário (s) que não foram relatados até agora para este gênero. Usando um sistema de cultura submerso, os metabólitos secundários foram recuperados por extrato de solvente seguido por cromatografia em camada delgada, ressonância magnética nuclear e espectroscopia de massa. Um novo metabólito secundário foi isolado de P. sclerotiorum (LM 5679); o composto fenólico 5-pentadecil resorcinol que é amplamente conhecido como um antifúngico que é produzido por diversas espécies de plantas. Este metabólito não foi relatado anteriormente em nenhuma espécie de Penicillium, e foi encontrado apenas uma vez em fungos (Fusarium). Aqui, discutimos as atividades conhecidas do 5-pentadecil resorcinol no contexto de seu modo de ação como um estressor hidrofóbico (mediado pela caotropicidade).

Plant metabolite 5-pentadecyl resorcinol is produced by the Amazonian fungus Penicillium sclerotiorum LM 5679 / O metabólito vegetal 5-pentadecil resorcinol é produzido pelo fungo amazônico Penicillium sclerotiorum LM 5679

Since the classic studies of Alexander Flemming, Penicillium strains have been known as a rich source of antimicrobial substances. Recent studies have identified novel metabolites produced by Penicillium sclerotiorum that have antibacterial, antifouling and pharmaceutical activities. Here, we report the isolation of a P. sclerotiorum (LM 5679) from Amazonian soil and carry out a culture-based study to determine whether it can produce any novel secondary metabolite(s) that are not thus-far reported for this genus. Using a submerged culture system, secondary metabolites were recovered by solvent extract followed by thin-layer chromatography, nuclear magnetic resonance, and mass spectroscopy. One novel secondary metabolite was isolated from P. sclerotiorum (LM 5679); the phenolic compound 5-pentadecyl resorcinol widely known as an antifungal, that is produced by diverse plant species. This metabolite was not reported previously in any Penicillium species and was only found once before in fungi (that time, in a Fusarium). Here, we discuss the known activities of 5-pentadecyl resorcinol in the context of its mode-of-action as a hydrophobic (chaotropicity-mediated) stressor.

Desde os estudos clássicos de Alexander Flemming, as cepas de Penicillium são conhecidas como uma fonte rica em substâncias antimicrobianas. Estudos recentes identificaram novos metabólitos produzidos pela espécie Penicillium sclerotiorum com atividades antibacteriana, anti-incrustante e farmacêutica. Aqui, relatamos o isolamento de uma colônia de P. sclerotiorum (LM 5679) do solo amazônico e relatamos também o estudo baseado em cultura para determinar se ele pode produzir qualquer novo metabólito (s) secundário (s) que não foram relatados até agora para este gênero. Usando um sistema de cultura submerso, os metabólitos secundários foram recuperados por extrato de solvente seguido por cromatografia em camada delgada, ressonância magnética nuclear e espectroscopia de massa. Um novo metabólito secundário foi isolado de P. sclerotiorum (LM 5679); o composto fenólico 5-pentadecil resorcinol que é amplamente conhecido como um antifúngico que é produzido por diversas espécies de plantas. Este metabólito não foi relatado anteriormente em nenhuma espécie de Penicillium, e foi encontrado apenas uma vez em fungos (Fusarium). Aqui, discutimos as atividades conhecidas do 5-pentadecil resorcinol no contexto de seu modo de ação como um estressor hidrofóbico (mediado pela caotropicidade).

Forma aguda de histoplasmose em paciente imunocompetente: relato de caso / Acute form of histoplasmosis in immunocompetent patient: case report

A histoplasmose é uma doença granulomatosa infecciosa sistêmica cuja transmissão é aerógena e a contaminação se dá pelo contato com fezes de aves e morcegos, depende da exposição e da imunidade do paciente. Trata-se de uma doença com difícil diagnóstico, dada a semelhança dos sintomas com os de outras doenças granulomatosas infecciosas, principalmente em pacientes imunocompetentes, visto que a regressão é geralmente espontânea. Um homem de 34 anos, branco, natural e procedente de Atibaia, previamente hígido, iniciou quadro de dor e edema no tornozelo esquerdo, e evoluiu com dispneia progressiva, com piora ao decúbito, acompanhada de sudorese noturna, tosse seca e febre baixa. Foi realizado o exame de tomografia computadorizada (TC) de tórax sem contraste, que evidenciou espessamento difuso das paredes brônquicas, de aspecto inflamatório, micronódulos esparsos bilateralmente. Paciente apresentou PCR elevado, COVID, sorologias, BAAR e hemoculturas negativas, punção articular e ecocardiograma sem alterações. Optado por COXCIP 4, sulfametoxazol-trimetoprim e anfotericina B de forma empírica. Pesquisa de fungos em escarro positivo; leveduras e lavado brônquico sugestivos de histoplasmose. Evoluiu com insuficiência respiratória necessitando de intubação orotraqueal, posteriormente, traqueostomia e apesar do tratamento antifúngico, evoluiu com óbito após 21 dias. A histoplasmose é uma doença grave, com diversas formas clínicas e prognóstico normalmente autolimitado, mas que pode ser fatal, mesmo em pacientes previamente imunocompetentes.

Histoplasmosis is a systemic infectious granulomatous disease whose transmission is airborne, and contamination occurs through contact with bird and bat feces, depending on the exposure and immunity of the patient. It is a disease with difficult diagnosis, given the similarity of symptoms with those of other infectious granulomatous diseases, especially in immunocompetent patients since regression is usually spontaneous. A 34-year-old Caucasian man from Atibaia, previously healthy, developed pain and swelling in his left ankle, progressing to progressive dyspnea, worsening in recumbency, accompanied by night sweats, dry cough and low-grade fever. A non-contrast-enhanced computed tomography (CT) scan of the chest was performed, which showed diffuse thickening of the bronchial walls, with an inflammatory appearance, and bilaterally sparse micronodules. Patient had high C-reactive protein, COVID, serology, BAAR and negative blood cultures, joint puncture, and echocardiogram without changes. Empirically opted for COXCIP 4, trimethoprim-sulfamethoxazole and amphotericin B. Search for fungi in positive sputum, yeasts, and bronchial lavage suggestive of histoplasmosis. He envolved with respiratory failure requiring orotracheal intubation, later tracheostomy and despite antifungal treatment, he died after 21 days. Histoplasmosis is a serious disease, with several clinical forms and a prognosis that is usually self-limiting, but it can be fatal, even in previously immunocompetent patients

Especies y sensibilidad a antifúngicos de cepas de Candida spp. aisladas de la cavidad bucal de pacientes con VIH de Paraguay

RESUMEN Candida albicans es la levadura más aislada de la cavidad oral de personas con VIH. Sin embargo, el uso de antifúngicos ha incrementado el aislamiento de especies no C. albicans resistentes o con sensibilidad reducida. El objetivo del estudio fue determinar las especies de Candida y la sensibilidad a los antifúngicos de aislamientos de la cavidad bucal de pacientes con VIH, que acudieron al Instituto de Medicina Tropical entre julio a diciembre de 2019. Las levaduras se sembraron en Agar Cromogénico Candida (CONDA®, España) para la identificación presuntiva. Las colonias verdes se identificaron por PCR dúplex y las de coloración distinta o PCR negativa mediante el sistema comercial VITEK®2. La susceptibilidad antifúngica de C. albicans se determinó por VITEK®2, y las no albicans por el método de difusión de discos. De 278 levaduras, C. albicans se aisló en 70,9 %, seguido de C. tropicalis (8,3 %) y C. krusei (5 %). C. albicans presentó 93 % de sensibilidad y 2 % de sensibilidad dosis dependiente al fluconazol; 87 % sensibles y 3 % con sensibilidad intermedia frente a voriconazol; 97, 98 y 100 % sensibilidad a flucitosina, anfotericina B y equinocandinas, respectivamente. C. parapsilosis y C. tropicalis no registraron resistencias a fluconazol y voriconazol. Todos los aislamientos de C. glabrata fueron sensibles dosis dependientes a fluconazol y todos los aislamientos de C. krusei resultaron sensibles a voriconazol. La portación oral de Candida spp. resistentes a azoles podría llevar a fracasos terapéuticos en pacientes con VIH que desarrollen candidiasis orofaríngea.

ABSTRACT Candida albicans is the most isolated yeast from the oral cavity of people with HIV. However, the use of antifungals has increased the isolation of non-C. albicans resistant species or those with reduced sensitivity. The objective of the study was to determine the Candida species and the sensitivity to antifungals of isolates from the oral cavity of patients with HIV who attended the Institute of Tropical Medicine between July and December 2019. The yeasts were plated in Candida Chromogenic Agar (CONDA®, Spain) for presumptive identification. Green colonies were identified by duplex PCR and those with different staining or negative PCR using the commercial VITEK®2 system. The antifungal susceptibility of C. albicans was determined by VITEK®2, and non albicans by the disk diffusion method. Of 278 yeasts, C. albicans was isolated in 70.9 %, followed by C. tropicalis (8.3 %) and C. krusei (5 %). C. albicans presented 93 % sensitivity and 2 % dose-dependent sensitivity to fluconazole; 87 % sensitive and 3 % intermediate sensitivity to voriconazole; 97, 98, and 100 % sensitive to flucytosine, amphotericin B, and echinocandins, respectively. C. parapsilosis and C. tropicalis did not register resistance to fluconazole and voriconazole. All C. glabrata isolates were dose-dependently sensitive to fluconazole and all C. krusei isolates were sensitive to voriconazole. The oral carriage of Candida spp. resistant to azoles may lead to therapeutic failures in HIV patients who develop oropharyngeal candidiasis.

Avaliação in vitro do potencial antifúngico de sais imidazólicos frente à Candida albicans / In vitro evaluation of antifungal potential of imidazolium salts against Candida albicans

Objetivo: O objetivo deste estudo foi avaliar o potencial antifúngico de um conjunto de sais imidazólicos (SI) frente a Candida albicans. Materiais e métodos: A avaliação an-tifúngica dos SI foi realizada por meio do teste de difusão em ágar, utilizando uma cepa de Candida albicans (ATCC 90028). Cinco diferentes SI foram sintetizados e testados no presente estudo: brometo de 1,8-bis(metilimidazólio-1-il) octano (MImC8MImBr2), metanossulfonato de 1,12-bis(-metilimidazólio-1-il) dodecano (MImC12MIm(MeS)2), clo-reto de 1-n-hexadecil-2,3-dimetilimidazólio (C16DMImCl), metanossulfonato de 1,10-bis(metilimidazólio-1-il) decano (MImC10MIm(MeS)2) e brometo de 1,10-bis(metilimidazólio--1-il) decano (MImC10MImBr2). O cloreto de cetilpiridíneo (C16PyrCl) foi utilizado como composto de referência e as soluções de digluconato de clorexidina (C34H54Cl2N10O14) e salina (NaCl 0,9%) foram utilizadas como controles po-sitivo e negativo, respectivamente. Resultados: Dentre os SI testados, MImC12MIm(MeS)2, MImC10MIm(MeS)2 e MImC10MImBr2 apresentaram os seguintes valores para os halos de inibição formados: 28,00 mm, 20,50 mm e 18,75 mm, respectivamente. Esses valores foram similares ou superiores inclusive aos encontrados para o controle positivo (14,87 mm) e o composto de referência (0 mm). Discussão: Os SI podem apresentar uma alternativa promissora às terapias com antifúngicos convencionais, concordando com estudos prévios. Entretanto, mais estudos in vitro e in vivosão necessários para avaliar o potencial antifúngico destes compostos frente a biofilmes multiespécies de C. albicans. Conclusão: Baseado nestes resultados, três dos SI testados apresentam atividade antifúngica in vitro promissora frente à Candida albicans.

Aim: This study aims to evaluate the antifungal potential of imidazolium salts (IS) against Candida albicans. Material and methods: Antifungal evaluation of the IS was perfor-med using the disk diffusion test, using a strain of Candida albicans (ATCC 90028). Five different IS were synthesized and tested in the present study: 1,8-bis(methylimidazolium-1-yl) octane bromide (MImC8MImBr2), 1,12-bis(methylimida-zolium-1-yl) dodecane methanesulfonate (MImC12MIm(-MeS)2), 1-n-hexadecyl-2,3-dimethylimidazolium chloride (C16DMImCl), 1,10-bis(methylimidazolium-1-yl) decane methanesulfonate (MImC10MIm(MeS)2) e 1,10-bis(me-thylimidazolium-1-yl) decane bromide (MImC10MImBr2). Cetylpyridinium chloride (C16PyrCl) was used as a reference substance. Chlorhexidine (C34H54Cl2N10O14) and saline (NaCl 0,9%) solutions were positive and negative controls, respectively. Results: Among the tested IS, MImC12MIm(-MeS)2, MImC10MIm(MeS)2 and MImC10MImBr2 showed the following values for inhibition halos: 28,00 mm, 20,50 mm and 18,75 mm, respectively. These values were similar or superior than those found for the positive control (14.87 mm) and reference (0 mm) substances. Discussion: IS can be a promising alternative to antifungal conventional therapies, as exemplified in previous studies. However, further in vitro and in vivo studies are needed to assess the antifungal potential of these compounds against Candida--mixed biofilms.Conclusion: Based on these results, three IS, tested in this study, have in vitro promissing antifungal potential against Candida albicans.