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)

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.

Preparation and antifungal activity of water-soluble graphene-based itraconazole antifungal eye drops / 中华实验眼科杂志

Objective:To prepare water-soluble graphene-based itraconazole antifungal eye drops and evaluate its antifungal activity against Fusarium solani. Methods:By oxidative modification of graphene and modification of polymer materials, water-soluble graphene oxide-modified polyethylene glycol (GO-PEG) composites were prepared.The composites were characterized by scanning electron microscopy, zeta potential, and Raman spectroscopy.The antifungal drug itraconazole was loaded onto the GO-PEG vector by solvent evaporation method, and itraconazole eye drops were obtained.The drug loading of itraconazole eye drops was measured using a UV and visible spectrophotometer.The antifungal effect in vitro was assessed by the microdilution method and light microscopy. Results:Scanning electron microscopy showed that GO-PEG had a two-dimensional nanosheet structure and many wrinkles.The zeta potential of GO-PEG was -42.40 mV.Raman spectroscopy showed that the ID/ IG of GO-PEG was 1.003.Using the water-soluble GO-PEG vector, a maximum itraconazole concentration of 10 mg/ml was achieved with a 10 000-fold increase in apparent solubility (10 mg/ml vs 0.001 mg/ml). The antifungal results showed that the minimum inhibitory concentration of itraconazole eye drops against Fusarium solani was approximately 1.88 μg/ml, but the GO-PEG vector has no significant antifungal activity against Fusarium solani. Conclusions:GO-PEG achieves effective loading and solubilization of itraconazole, demonstrating an in vitro inhibitory effect on Fusarium solani.

Controlling antifungal activity with light: Optical regulation of fungal ergosterol biosynthetic pathway with photo-responsive CYP51 inhibitors

Invasive fungal infections (IFIs) have been associated with high mortality, highlighting the urgent need for developing novel antifungal strategies. Herein the first light-responsive antifungal agents were designed by optical control of fungal ergosterol biosynthesis pathway with photocaged triazole lanosterol 14α-demethylase (CYP51) inhibitors. The photocaged triazoles completely shielded the CYP51 inhibition. The content of ergosterol in fungi before photoactivation and after photoactivation was 4.4% and 83.7%, respectively. Importantly, the shielded antifungal activity (MIC80 ≥ 64 μg/mL) could be efficiently recovered (MIC80 = 0.5-8 μg/mL) by light irradiation. The new chemical tools enable optical control of fungal growth arrest, morphological conversion and biofilm formation. The ability for high-precision antifungal treatment was validated by in vivo models. The light-activated compound A1 was comparable to fluconazole in prolonging survival in Galleria mellonella larvae with a median survival of 14 days and reducing fungal burden in the mouse skin infection model. Overall, this study paves the way for precise regulation of antifungal therapy with improved efficacy and safety.

Validation of a fast and reliable liquid chromatography tandem mass spectrometry for simultaneous quantitation of Voriconazole, Posaconazole and Linezolid in human serum / 中华检验医学杂志

Objective:To establish a high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of voliconazole (VRC), posaconazole (PCZ), and linazolam (LNZ) in human serum.Methods:This study is a methodological validation by LC-MS/MS. The blood concentration results of VRC, PCZ, and LNZ in our hospital′s anti-infection patients were collected. Voriconazole, Posaconazole, and Linezolid were accurately weighed and prepared. Linezolid-[2H3] was used as the internal standard. After gradient elution on the ACE PFP column, the residuals were analyzed by LC-MS/MS in the positive electrospray ionization mode and multiple reaction monitor (MRM) mode. The method′s linearity, precision, lower limit of detection, and recovery rate were validated according to standard guidelines.Results:The linear correlation coefficient ( r) of the standard curve was above 0.99 ( r>0.99). The linear range of VRC and PCZ were 0.10 mg/L~10.00 mg/L, and the lower limit of detection were 0.01 mg/L. The linear range of LNZ was 0.50 mg/L~50.00 mg/L, and the lower limit of detection was 0.05 mg/L. The recoveries of VRC, PCZ and LNZ were 90.96%-103.18%, 91.84%-99.17%, and 97.04%-100.41%, respectively. Intra-and inter-batch precision (% CV) for VRC were less than 8.30%. Intra-and inter-batch precision (% CV) for PCZ was less than 9.78%. Intra-and inter-batch precision (% CV) for LNZ was less than 7.14%. Drug concentrations in 155 cases of VRC, 44 cases of PCZ, and 59 cases of LNZ were detected. Conclusion:We have established an LC-MS/MS method for the rapid, accurate, highly specific determination of VRC, PCZ, and LNZ concentrations in human serum. This method is suitable for analyzing large clinical sample sets.

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.

Analysis of resistance and sensitivity of 1 200 strains of vulvovaginal candidiasis in China to five common antifungal drugs / 中华妇产科杂志

Objective:To test the antibiotic susceptibility of vulvovaginal candidiasis pathogenic strains to 5 antifungal drugs commonly used in clinic.Methods:A total of 1 200 vulvovaginal candida patients from 23 gynecological and family planning outpatient departments in China were enrolled. Their vaginal secretions were collected for candida strain isolation and species identification. According to Clinical and Laboratory Standards Institute (CLSI) M27-S3, the sensitivity of 1 200 strains to clotrimazole, fluconazole, miconazole, itraconazole and nystatin was tested.Results:(1) The sensitivity and resistance of 1 200 vulvovaginal candidiasis pathogens to 5 antifungal drugs were statistically different ( χ2=3 513.201, P<0.01). (2) All strains had higher sensitivity to nystatin [99.92% (1 199/1 200)], followed by miconazole [92.25% (1 107/1 200)] and clotrimazole [87.17% (1 046/1 200)]. All strains had higher resistance to fluconazole [69.17% (830/1 200)], while itraconazole was 50.83% (610/1 200). (3) There was no significant difference between candida albicans and non-candida albicans in drug sensitivity to nystatin ( P=0.315) and miconazole ( P=0.425). (4) Candida albicans and non-candida albicans showed different sensitivity to clotrimazole, fluconazole and itraconazole, respectively. Compared with non-candida albicans, candida albicans showed higher sensitivity to clotrimazole [susceptibility rate: 73.01% (165/226) vs 90.45% (881/974); P<0.001] and higher resistance to fluconazole [resistance rate: 50.88% (115/226) vs 73.41% (715/974); P<0.001]. Although the drug sensitivity of itraconazole was not high, the susceptibility rate of candida albicans to itraconazole was slightly higher than that of non-candida albicans [37.68% (367/974) vs 23.89% (54/226)], and the drug resistance rate was lower [49.28% (480/974) vs 57.52% (130/226)]. Conclusions:The sensitivity of 1 200 strains of candida to 5 antifungal drugs is significantly different, the sensitivity rate of nystatin, miconazole and clotrimazole are higher, but the resistance rate of fluconazole and itraconazole are higher. The sensitivity of candida albicans and non-candida albicans to the same drug is also significantly different. It is suggested that in clinical diagnosis and treatment, we should pay attention to the identification of candida and drug sensitivity test, so as to select antifungal drugs rationally.

In vitro activity of Schinus terebinthifolius extract and fractions against Sporothrix brasiliensis

BACKGROUND Sporothrix brasiliensis is the causative agent of zoonotic cases of sporotrichosis in Brazil and is associated with atypical and severe presentations in cats, dogs, and humans. Sporotrichosis treatment is usually time- and cost-consuming, sometimes with poor response and host toxicity. Schinus terebinthifolius has proven efficacy against bacteria and fungi of clinical interest. OBJECTIVE To determine the in vitro activity of S. terebinthifolius against S. brasiliensis. METHODS Five S. brasiliensis isolates and three reference strains were subjected to a hydroethanol extract derived from the leaves of S. terebinthifolius and its fractions. The minimal inhibitory concentration (MIC) was determined using the broth microdilution method according to the M38-A2 CLSI guidelines. Also, the fungicidal/fungistatic activity of the extract and fractions was studied. FINDINGS The crude extract of S. terebinthifolius inhibited the growth of S. brasiliensis (MIC: 0.5-1.0 µg/mL), while the partitioned extracts dichloromethane, ethyl acetate, and butanol demonstrated growth inhibition at 8 µg/mL due to a fungistatic activity. MAIN CONCLUSIONS Due to its in vitro efficacy against S. brasiliensis and its known pharmacological safety, S. terebinthifolius is a candidate to be tested using in vivo models of sporotrichosis.

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

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)

Distribution and antifungal susceptibility of Candida species isolated from clinical samples in southern Brazil

Abstract Invasive infections caused by Candida species have been strongly associated with poor prognosis and high resistance rates to some antifungals. This study aimed to identify Candida species isolated from different anatomical sites and to describe their susceptibility profile to antifungals. Ninety-four clinical isolates of Candida were obtained from a Medical Laboratory of Santa Catarina/Brazil. Species identification was performed by MALDI-TOF MS. Susceptibility assays were performed as described by Clinical Laboratory Standard Institute (CLSI) microboth method. Among the analyzed samples, C. albicans was the pathogen most incident (59.9%) followed by C. parapsilosis complex (14.9%), C. glabrata complex (8.5%), and C. tropicalis (6.3%). 37 Candida strains were isolated from vaginal content (39.3%), 21 from the nail (22.4%), 8 from tracheal aspirates (8.5%), and 7 from urine (7.4%). Together, the Candida isolates presented decreased susceptibility to azole drugs, mainly to fluconazole and itraconazole. Amphotericin B showed sensibility in 95.7% of samples analyzed. Previous knowledge about etiology and antifungal susceptibility becomes indispensable to conduct an efficient treatment.

Application of antifungal agents in special populations / 中华皮肤科杂志

Antifungal agents have shown good efficacy and tolerability in the general population. However, the antifungal treatment remains a great challenge in some special populations due to their special conditions, such as children, the elderly, pregnant women and patients with hepatic insufficiency. This review summarizes recommendations for the use of common antifungal agents in the above special populations.

Refinement review of the interactions between triazole antifungal agents and statins based on the optimization of the pre-prescription audit system / 药学实践杂志

Objective To better carries out the review of the interaction between triazole antifungal drugs and statins, ensure drug safety for patients and improve the efficiency of the manual review of pharmacists. Methods The advantageous combination with less interaction between the two kinds of drug was obtained by summarizing the interaction information of triazole antifungal drugs and statins. At the same time, optimizing the process of full manual reviews for drug interaction, and the advantageous combination of the two kinds of drug will be set up in advance on the doctor side of the review system. Doctors can adjust the drug in time according to the prompts of the information system when there is a significant interaction of the two kinds of drug in the prescription or medical order, which is issued by the doctors. Results After optimization, most doctors choose the drug combination of less interaction between the two kinds of drug according to the system prompts. The number of drug combinations of significant interaction which is manually reviewed by pharmacists is significantly reduced (P<0.05), and the review efficiency is improved, the drug safety risks brought by drug interactions to patients are reduced. Conclusion Refinement review of drug interactions between triazole antifungal agents and statins based on the optimization of the pre-audit system plays a positive role in improving the safety of patients’ medication and the efficiency of pharmacists' manual auditing.

Cryptococcus neoformans meningoencephalitis / 中华神经科杂志

Cryptococcal meningitis is a central nervous system infection caused by cryptococcal invasion of meninges and (or) brain parenchyma. It is characterized by severe intracranial hypertension and brain parenchyma damage. This opportunistic infection commonly occurs among HIV infected individuals, organ transplant recipients, and other immunosuppressive situations, and otherwise immunologically normal hosts. The global burden of human immunodeficiency virus/acquired immunodeficiency syndrome has declined over the years, but cryptococcal meningitis still has a high morbidity and mortality. The risk groups, clinical presentation, imaging characteristics, diagnostic criteria and therapeutic issues were reviewed in this article.

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.

Chemical composition, antimicrobial and antifungal activity of Lippia Thymoide essential oil in oral pathogens

Aim: This study evaluated the chemical composition of Lippia thymoides (Lt) essential oil and its antimicrobial activity against fungal strains of Candida albicans (Ca) and Gram-negative bacteria Prevotella intermedia (Pi) and Fusobacterium nucleatum (Fn). Methods: Lt essential oil was obtained by hydrodistillation apparatus with a modified Clevenger extension. The chemical analysis was analyzed by gas phase chromatography and mass spectrometry on Shimadzu QP 2010 plus. Sample sensitivity evaluation was performed by ABHb-inoculum and culture plates were developed with triphenyltetrazolium chloride, also Fn and Pi samples analysis were in anaerobic environment and Ca sample analysis was performed in aerobic environment. The minimum inhibitory concentration (CIM) was determinated by microdilution in eppendorfs tubes. Results: The chemical analysis showed that Thymol (59,91%) is the main compound found in Lt essential oil, also other antifungal and antimicrobial agents were present γ-terpinene (8.16%), p-cymene (7.29%) and ß-caryophyllene (4.49%), Thymol is a central ingredient of many medicinal plants and has a potent fungicidal, bactericidal and antioxidant activity, it has been previously shown to have anti-inflammatory activity against Periodontal Disease (PD) cause can reduces prostanoids, interleukins, leukotrienes levels in periodontium. CIM result Pi was 6.5 µg/mL, Fn was 1.5 µg/mL and Ca was 0.19 µg/mL. Conclusion: The antimicrobial activity of L. thymoides, through the compound Thymol, has been shown promising potential against gram-negative periodontopathogenic bacteria and fungi whose therapeutic arsenal is still very restricted

Phytochemical composition, antifungal activity, in vitro and in vivo toxicity of Syzygium cumini (L) Skeels leaves extract / Composición fitoquímica, actividad antifúngica, toxicidad in vitro e in vivo del extracto de hojas de Syzygium cumini (L) Skeels

This study determined phytochemical composition, antifungal activity and toxicity in vitro and in vivo of Syzygium cumini leaves extract (Sc). Thus, was characterized by gas chromatography coupled to mass spectrometry and submitted to determination of Minimum Inhibitory (MIC) and Fungicidal concentrations (MFC) on reference and clinical strains of Candida spp. and by growth kinetics assays. Toxicity was verified using in vitro assays of hemolysis, osmotic fragility, oxidant and antioxidant activity in human erythrocytes and by in vivo acute systemic toxicity in Galleria mellonella larvae. Fourteen different compounds were identified in Sc, which showed antifungal activity (MIC between 31.25-125µg/mL) with fungistatic effect on Candida. At antifungal concentrations, it demonstrated low cytotoxicity, antioxidant activity and neglible in vivotoxicity. Thus, Sc demonstrated a promising antifungal potential, with low toxicity, indicating that this extract can be a safe and effective alternative antifungal agent.

Este estudio determinó la composición fitoquímica, la actividad antifúngica y la toxicidad in vitro e in vivo del extracto de hojas de Syzygium cumini (Sc). Así, se caracterizó mediante cromatografía de gases acoplada a espectrometría de masas y se sometió a determinación de Concentraciones Mínimas Inhibitorias (CMI) y Fungicidas (MFC) sobre cepas de referencia y clínicas de Candida spp. y mediante ensayos de cinética de crecimiento. La toxicidad se verificó mediante ensayos in vitro de hemólisis, fragilidad osmótica, actividad oxidante y antioxidante en eritrocitos humanos y por toxicidad sistémica aguda in vivo en larvas de Galleria mellonella. Se identificaron catorce compuestos diferentes en Sc, que mostraron actividad antifúngica (CMI entre 31.25-125 µg/mL) con efecto fungistático sobre Candida. En concentraciones antifúngicas, demostró baja citotoxicidad, actividad antioxidante y toxicidad in vivo insignificante. Por lo tanto, Sc demostró un potencial antifúngico prometedor, con baja toxicidad, lo que indica que este extracto puede ser un agente antifúngico alternativo seguro y eficaz.

Mucormicosis cutánea extensa: reporte de caso

La mucormicosis es una enfermedad oportunista causada por un grupo de hongos filamentosos del subfilo Mucormycotina, tiene una presentación clínica variada: rino-orbito-cerebral, pulmonar, cutánea, gastrointestinal, diseminada y de sitios poco frecuentes. La mucormicosis cutánea se presenta en el 19% de los casos. Se presenta un caso de mucormicosis cutánea extensa en un paciente adulto joven, luego de quemadura por sustancia desconocida y aplicación de emplastos medicinales herbales. Tras recibir curaciones en varias oportunidades en un establecimiento de salud fue referido a un hospital de nivel 3 donde se le realizó limpieza quirúrgica y administración de antibióticos por vía endovenosa, sin mejoría clínica. Se le realizó estudio histológico de la piel afectada, cuyo informe fue inflamación intensa mixta a nivel del tejido subcutáneo, con moderado predominio de granulocitos, focos de necrosis grasa en parches, con variable inflamación. En el interior de los adipocitos necróticos, se observaron algunas estructuras con morfología de hifas fúngicas anchas, de contorno irregular morfológicamente consistentes con mucor. El paciente recibió antifúngicos combinados con curas quirúrgicas del tejido afectado en varias oportunidades, sin detener progresión de la infección. El paciente falleció.

SUMMARY Mucormycosis is an opportunistic disease caused by a group of filamentous fungi of the subphylum Mucormycotina, it has a varied clinical presentation: rhino-orbito-cerebral, pulmonary, cutaneous, gastrointestinal, disseminated and with infrequent sites. Cutaneous mucormycosis occurs in 19% of cases. A case of extensive cutaneous mucormycosis is presented in a young adult patient, after a burn caused by an unknown substance and the application of herbal medicinal plasters. After receiving cures on several occasions in a health facility, he was referred to a level 3 hospital where he underwent surgical cleaning plus administration of intravenous antibiotics, without clinical improvement; A histological study of the affected skin was performed, where intense mixed inflammation is reported at the subcutaneous tissue level, with a moderate predominance of granulocytes; as well as foci of fat necrosis in patches, with variable inflammation. Inside the necrotic adipocytes, there are some structures with wide fungal hyphae morphology, with an irregular contour morphologically consistent with mucor. The patient received antifungals combined with surgical cures of the affected tissue on several occasions, without stopping the progression of the infection; patient dies.

Nanopartículas de plata en el tratamiento de la micosis asociada al pie diabético / Silver nanoparticles to treat mycosis associated with diabetic foot / Nanopartículas de prata no tratamento da micose associada ao pé diabético

Resumen: Una proporción importante de infecciones en el pie diabético consisten en onicomicosis y tinea pedis, problema común en el pie, amenazante de la viabilidad del tejido que puede provocar infecciones bacterianas secundarias. Requieren períodos prolongados de tratamiento antimicótico con alta tasas de recaídas y reinfección. Diversos estudios han mostrado la seguridad y eficacia de las nanopartículas de plata (NP Ag) como agente antimicrobiano. Realizamos un estudio donde se evaluó el tratamiento con NP Ag en dermatomicosis del pie de pacientes diabéticos. Método: estudio piloto, abierto, prospectivo, randomizado y controlado en pacientes que asisten a una policlínica de pie diabético. Dieciocho pacientes cumplieron con los criterios de inclusión conformándose dos grupos homogéneos. Ambos grupos recibieron tratamiento estándar que consistió en antimicótico tópico y desbastado mecánico. El grupo intervención utilizó un textil (medias) confeccionadas con hilos con NP Ag. Se realizó control clínico y microbiológico hasta las 12 semanas. Se evaluó el porcentaje de remisión y el tiempo hasta alcanzar el mismo. Resultados: predominó la onicomicosis y el germen Trichophyton rubrum. En el grupo intervención se logró un mayor porcentaje de remisión de lesiones y en un tiempo menor que el grupo control. Conclusiones: el uso de medias confeccionadas con hilos de NP Ag se asoció con una mayor probabilidad de curación completa en un período de 12 semanas a pesar de que el número de pacientes no permitió llegar al nivel de significación estadística, pudiendo contribuir a la prevención de infecciones o úlceras suplementarias en el pie diabético.

Summary: Onychomycosis and tinea pedis represent a significant proportion of infections in the diabetic foot, a common foot problem, and they constitute a threat to the viability of tissues that may provoke secondary bacterial infections. To combat them, antifungal treatments are required for long periods of time, the rates of relapse and reinfection being high. Several studies have proved the safety and effectiveness of silver nano particles (NP Ag) as an antimicrobial agent. A study was conducted to assess nanoparticle agents for foot dermatomycosis in diabetic patients. Method: pilot, open, prospective randomized and controlled study in patients who are assisted in a diabetic foot policlinic. 18 patients complied with the inclusion criteria and two homogeneous groups were formed. Both groups received standard treatment consisting in topic antifungal and mechanical roughing. The intervention groups used a textile (stockings) made with silver nanoparticle threads. Clinical and microbiological control was made during 12 weeks, also assessing the remission percentage and the time it took to achieve it. Resultados: onychomycosis and trichophyton rubrum prevailed. The intervention group showed a greater percentage of remission of lesions in a period of time that was shorter than that of the control group. Conclusions: the use of stockings made with NP Ag threads was associated with a greater probability of complete healing, in a 12-week period, despite the fact that the number of patients was not statistically significant. This could contribute to the prevention of supplementary infections or ulcers in the diabetic foot.

Resumo: Uma proporção significativa de infecções do pé diabético consiste em onicomicose e Tinea pedis, um problema comum nos pés que ameaça a viabilidade do tecido e pode causar infecções bacterianas secundárias. Requerem períodos prolongados de tratamento antifúngico com altas taxas de recidiva e reinfecção. Vários estudos têm demonstrado a segurança e a eficácia das nanopartículas de prata (NP Ag) como agente antimicrobiano. Realizamos um estudo onde o tratamento com NP Ag foi avaliado na dermatomicose do pé de pacientes diabéticos. Método: estudo piloto, aberto, prospectivo, randomizado e controlado em pacientes atendidos em uma policlínica de pé diabético. Dezoito pacientes preencheram os critérios de inclusão, formando dois grupos homogêneos. Ambos os grupos receberam tratamento padrão que consiste em antifúngico tópico e moagem mecânica. O grupo intervenção utilizou um tecido (meias) confeccionado com fios NP Ag. O controle clínico e microbiológico foi realizado até 12 semanas. A porcentagem de remissão e o tempo para alcançá-la foram avaliados. Resultados: predominaram a onicomicose e o germe Trichophyton rubrum. No grupo intervenção, obteve-se maior percentual de remissão das lesões e em menor tempo que o grupo controle. Conclusões: o uso de meias confeccionadas com fios NP Ag esteve associado a uma maior probabilidade de cura completa, no período de 12 semanas, apesar do número de pacientes não permitir atingir o nível de significância estatística, podendo contribuir para a prevenção de infecções ou úlceras adicionais no pé diabético.

Evaluation of susceptibility and response in the surface of agents of surface mycoses (Trichophyton mentagrophytes; T. tonsurans) to antifungal drugs of interest in a medical clinic / Avaliação da susceptibilidade e resposta in vitro de agentes de micoses superficiais (Trichophyton mentagrophytes; T. tonsurans) à drogas antifúngicas de interesse em clínica médica

INTRODUCTION: The resistance of fungal species to drugs usually used in clinics is of great interest in the medical field. OBJECTIVE: To evaluate susceptibility and in vitro response of species of Trichophyton spp. to antifungal drugs of interest in clinical medicine. METHODS: 12 samples of clinical isolates from humans were used, nine of T. mentagrophytes and three of T. tonsurans. Susceptibility tests were performed according to the agar diffusion (AD) and broth microdilution (BM) methods. RESULTS: In the AD method, the species T. tonsurans presented a percentage of sensitivity of 33% in relation to amphotericin B and 66% to itraconazole, with 100% resistance to ketoconazole and fluconazole. T. mentagrophytes also showed 100% resistance to ketoconazole in this technique, with 11% sensitivity to ketoconazole, 22% to itraconazole and 22% of samples classified as sensitive dose dependent. In the MC method, the species T. tonsurans presented a sensitivity percentage of 66%, 55% and 33% in relation to ketoconazole, fluconazole and itraconazole, respectively. The T. mentagrophytes species presented sensitivity percentages of 11%, 11%, 33% and 55% for amphotericin B, itraconazole, ketoconazole and fluconazole, respectively. CONCLUSION: There was resistance in vitro of the species of T. mentagrophytes and T. tonsurans against the antifungal fluconazole and relative resistance against ketoconazole in the AD method. In BM, however, important percentages of sensitivity were observed for the two species analyzed in relation to the antifungals fluconazole and ketoconazole when compared to itraconazole and amphotericin B.

INTRODUÇÃO: A resistência de espécies fúngicas às drogas usualmente empregadas no meio clínico é motivo de grande interesse na área médica. OBJETIVO: Avaliar susceptibilidade e resposta in vitro de espécies de Trichophyton spp. a drogas antifúngicas de interesse em clínica médica. MÉTODOS: Foram utilizadas 12 amostras de isolados clínicos de humanos, sendo nove de T. mentagrophytes e três de T. tonsurans. Foram realizados testes de susceptibilidade segundo os métodos de difusão em ágar (DA) e microdiluição em caldo (MC). RESULTADOS: No método de DA, a espécie T. tonsurans apresentou percentual de sensibilidade de 33% em relação à anfotericina B e de 66% ao itraconazol, com 100% de resistência frente ao cetoconazol e ao fluconazol. A espécie T. mentagrophytes também apresentou 100% de resistência frente ao cetoconazol nesta técnica, com 11% de sensibilidade ao cetoconazol, 22% ao itraconazol e 22% das amostras classificadas como sensível dose dependente. No método de MC, a espécie T. tonsurans apresentou percentual de sensibilidade de 66%, 55% e 33% em relação ao cetoconazol, fluconazol e itraconazol, respectivamente. A espécie T. mentagrophytes apresentou percentuais de sensibilidade de 11%, 11%, 33% e 55% para anfotericina B, itraconazol, cetoconazol e fluconazol, respectivamente. CONCLUSÃO: Houve resistência in vitro das espécies do T. mentagrophytes e T. tonsurans frente ao antifúngico fluconazol e resistência relativa frente ao cetoconazol no método de DA. Na MC, no entanto, foram observados importantes percentuais de sensibilidade das duas espécies analisadas frente aos antifúngicos fluconazol e cetoconazol quando comparadas ao itraconazol e à anfotericina B.