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.

Aspergilosis pulmonar invasiva en paciente pediátrico / Invasive pulmonary aspergillosis in a pediatric patient

La creciente emergencia de las enfermedades infecciosas y el aumento del número de individuos que tienen afectada su competencia inmunológica se ha convertido en un reto. Por otro lado, considerando el género Aspergillus, como un agente etiológico de infección, causa importante de morbilidad y mortalidad en pacientes inmunocomprometidos. Presentamos el caso de preescolar femenino de 3 años y 8meses con antecedente de teratoma maduro fetiforme, quien posterior a 6 meses de su exéresis, se realiza tomografía axial computarizada (TAC) de Tórax control evidenciándose bronquiectasias centrales con opacidades tubulares y saculares de distribución bronquial, con localización principalmente en lóbulo superior de hemitórax izquierdo, disminución del volumen pulmonar ipsilateral con incipiente desplazamiento del cardiomediastino a la izquierda y escaso derrame pleural izquierdo, examen físico sin alteraciones, por lo que ingresa con diagnóstico de enfermedad granulomatosa en estudio. Se realiza detección de antígeno galactomanano que reporta positivo en dos determinaciones por lo que se replantea el diagnóstico a Aspergilosis Pulmonar Invasiva, cumple tratamiento con voriconazol por 21 días, con mejoría significativa de las lesiones pulmonares en TAC de tórax, egresando con tratamiento con itraconazol a cumplir por 6 semanas. El inicio precoz del tratamiento constituye un factor pronóstico fundamental de la aspergilosis invasiva, siendo el voriconazol la primera línea(AU)

The growing emergence of infectious diseases and increasing the number of individuals that have affected their immune competence has be come a challenge. Furthermore, considering the genus Aspergillus, as an etiologic agent of infection, which causes significant morbidity and mortality in immunocompromised patients. We present a case of a female preschool 3 years and 8 months with a history of matureteratoma fetiforme, who after 6 months of excision, compute dtomography (CT) scan control is performed where central bronchiectasis are evident with tubular opacities and saculares bronchial distribution, located mainly in the upper lobe of left chest, decreased left lung volume with incipient displacement of the heart and medistino left and low left pleural effusion, physical examination no alterations to income, so you enter with diagnosis of granulomatous disease study. antigen detection galactomannan reporting positive in two determinations so the diagnosis of invasive pulmonary aspergillosis rethinks meets voriconazole for 21 days, with significant improvement of lunglesions in chest CT scan, graduating with itraconazole therapy is performed to meet for 6 weeks. The early initiation of treatmentis a fundamental prognostic factor of invasive aspergillosis, constituting the first line in voriconazole(AU)

Esporotricosis linfocutánea en un paciente pediátrico, a propósito de un caso / Lymphocutaneous sporotrichosis in a pediatric patient, a case report

Resumen La esporotricosis es una infección fúngica de evolución subagudacrónica causada por hongos dimórficos del Complejo Sporothrix schenckii. Es más frecuente en zonas tropicales. La prevalencia en Argentina se estima entre 0,01 y 0,02%. En la mitad de los pacientes se manifiesta como una esporotricosis linfocutánea, la cual se produce tras la inoculación del hongo en la piel luego de un trauma menor. La lesión inicial es una pápula o nódulo que se sucede con la aparición de una cadena ascendente de nódulos subcutáneos móviles, indoloros y eritematosos. El diagnóstico se realiza a partir del cultivo micológico. El antifúngico de elección es itraconazol y el pronóstico es usualmente favorable. Se presenta el caso de una niña de 4 años, previamente sana, que consultó por adenopatías axilares de evolución subaguda sin respuesta a múltiples esquemas antimicrobianos, confirmándose el diagnóstico de una esporotricosis linfocutánea por el cultivo de una biopsia ganglionar.

Abstract Sporotrichosis is a subacute-chronic fungal infection caused by dimorphic fungi of the Sporothrix schenckii Complex. It is more common in tropical areas. The prevalence in Argentina is estimated between 0.01 and 0.02%. In half of the patients it manifests as lymphocutaneous sporotrichosis, which occurs after inoculation of the fungus into the skin after minor trauma. The initial lesion is a papule or nodule that occurs with the appearance of an ascending chain of mobile, painless and erythematous subcutaneous nodules. The diagnosis is made from mycological culture. The antifungal of choice is itraconazole and the prognosis is usually favorable. We present the case of a healthy 4-year-old girl who consulted for subacute axillary lymphadenopathy without response to multiple antimicrobial regimens, arriving at the diagnosis of lymphocutaneous sporotrichosis from the culture of a lymph node biopsy sample.

Histoplasmosis bucal / Oral histoplasmosis

Introducción: La histoplasmosis es una micosis causada por Histoplasma capsulatum. Este hongo se encuentra en las excretas de algunos animales (murciélagos y aves) y su reservorio es el suelo. Es una enfermedad endémica en el continente americano. La inhalación de esporas causa infección pulmonar primaria que puede diseminarse. Objetivo: Describir un caso de histoplasmosis bucal en un paciente seronegativo al virus de inmunodeficiencia humana. Caso clínico: Paciente diabético, fumador y alcohólico con cuadro febril de varios meses acompañado de manifestaciones respiratorias. Además, se constataron úlceras en encías y lengua, lesiones nodulares en mucosas del carrillo, fondo del surco vestibular y reborde alveolar. Se informó anemia, leucopenia y aumento de la velocidad de sedimentación globular. El diagnóstico se confirmó mediante citología e histopatología. La terapéutica empleada fue itraconazol 200 mg tres veces al día, luego 200 mg dos veces al día por dos meses y una tableta diaria hasta seis meses después del segundo mes. El paciente se encuentra asintomático y las lesiones bucales desaparecieron. Conclusiones: La histoplasmosis se diagnostica fundamentalmente por la epidemiología, la clínica y el cultivo. Los estudios citopatológicos e histopatológicos de la úlcera confirman el diagnóstico. Este caso representa una forma no habitual de presentación de la enfermedad, que aunque no se sospecha usualmente, puede ocurrir. Este trabajo es una alerta a los estomatólogos, maxilofaciales y a todo aquel personal de la salud que asiste a pacientes con manifestaciones sistémicas(AU)

Introduction: Histoplasmosis is a mycosis caused by Histoplasma capsulatum. This fungus is found in the feces of some animals (bats and birds) and its reservoir is the soil. Histoplasmosis is an endemic disease in the American continent. Inhalation of spores causes primary pulmonary infection, which may in turn be disseminated. Objective: Describe a case of oral histoplasmosis in a patient seronegative to the human immunodeficiency virus. Clinical case: A case is presented of a diabetic, smoker and alcoholic patient with fever of several months' evolution and respiratory manifestations. Examination revealed ulcers in the patient's gums and tongue, as well as nodular lesions in the mouth mucosa, the bottom of the vestibular sulcus and the alveolar ridge. Laboratory testing found anemia, leucopenia and an increased globular sedimentation rate. The diagnosis was confirmed by cytology and histopathology. The treatment indicated was 200 mg itraconazole three times a day and then 200 mg twice a day for two months, and a daily tablet for six months after the second month. The patient is now asymptomatic and the oral lesions have disappeared. Conclusions: Histoplasmosis is mainly diagnosed by epidemiological testing, clinical examination and culture. Cytopathologic and histopathological analysis of the ulcer confirm the diagnosis. The case illustrates an infrequent form of presentation of the disease, not usually suspected but possible. The study is a warning to dentists, maxillofacial specialists and all the health personnel caring for patients with systemic manifestations(AU)

Histoplasmosis: informe de un caso / Histoplasmosis: a case report

Objetivo: Describir el diagnóstico y el tratamiento interdisciplinario de un caso clínico de histoplasmosis. Caso clínico: Un paciente masculino de 39 años, con antecedentes de consumo de drogas, alcohol, tabaquismo crónico y VIH+ sin adherencia al tratamiento, acudió al Servicio de Odontología por una interconsulta del Servicio de Clínica Médica para la evaluación de lesiones erosivas en paladar duro y blando, reborde alveolar anterior, dorso lingual y lesión tumoral en encía anterosuperior. El diagnóstico definitivo se obtuvo por medio del análisis de muestras de biopsia transbronquial, lavado broncoalveolar y biopsia de lesión en piel. El paciente recibió tratamiento sistémico con antimicóticos (anfotericina B e itraconazol según esquema) y tratamiento local con colutorio de clorhexidina al 0,12% y 100.000 UI de nistatina en suspensión. Al momento del alta, presentaba una considerable mejoría de su estado general y de las lesiones orales, con disminución de sintomatología dolorosa. Se indicó turno para control a los 7 días de forma ambulatoria, al cual el paciente no asistió. El abordaje interdisciplinario y el análisis de los diferentes aspectos socioeconómicos, culturales, ambientales y sistémicos del paciente facilitaron el diagnóstico temprano de la enfermedad (AU)

Aim: To describe the diagnosis and interdisciplinary treatment of a clinical case of histoplasmosis. Clinical case: 39-year-old male patient with a history of drug abuse, alcohol, and chronic smoking, HIV+ without treatment compliance, attends the dental department referred by the medical department for the diagnosis of erosive lesions in the hard and soft palate, anterior alveolar ridge, lingual dorsum and tumor lesion in the anterosuperior gingiva. The definitive diagnosis was obtained by the analysis of transbronchial biopsy, bronchoalveolar lavage and skin lesion biopsy. The patient received systemic treatment with antifungals (amphotericin b, itraconazole according to protocol), and local treatment with 0.12% chlorhexidine mouthwash and 100,000 IU nystatin suspension. At the time of medical discharge, the patient presented a considerable improvement in his general condition and of the oral lesions with a reduced pain. A 7 days recall was prescribed, however the patient failed to attend. The interdisciplinary approach to the patient and the analysis of the different socio-economic, cultural, environmental and systemic aspects of the patient facilitates the early diagnosis of the disease (AU)

Sporotrichosis refractory to conventional treatment: therapeutic success with potassium iodide

Abstract Sporotrichosis is a subcutaneous mycosis caused by dimorphic fungi of the genus Sporothrix. The authors report a case of fixed cutaneous sporotrichosis with therapeutic failure after 18 months of itraconazole and terbinafine associated with cryosurgery. The patient was cured after the introduction of saturated potassium iodide solution. Sporothrix brasiliensis was the identified species, presenting a susceptibility profile to itraconazole and terbinafine. This fact suggests that therapeutic failure is probably related to the host-fungus interaction rather than drug resistance. It is possible that the immunomodulatory action of the saturated potassium iodide solution may have played an important role in curing this patient.

Granulomatous tracheitis and dermatitis due to Curvularia sp. in a horse: case report / [Traqueíte e dermatite granulomatosas associadas a Curvularia sp. em um equino: relato de caso]

Tracheal fungal infections in horses are rare. This case report describes surgical and clinical management of a filly with a Curvularia sp. infection within the trachea and skin that caused severe intraluminal granulomas and cutaneous nodules, respectively. The patient was successfully treated with itraconazole and surgical excision.(AU)

Infecções fúngicas traqueais em equinos são raras. Este relato de caso descreve condutas clínicas e cirúrgicas em uma égua com infecção por Curvularia sp. na traqueia e na pele, causando granulomas intraluminais severos e nódulos cutâneos, respectivamente. O animal foi tratado com sucesso com itraconazol e exérese cirúrgica.(AU)

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.

Intestinal Paracoccidioidomycosis: Case report and systematic review

ABSTRACT Background: Paracoccidioidomycosis is a systemic mycosis considered endemic and limited to Latin America with the majority of registered cases originating from Brazil. The purpose of this paper was to report a case of a female patient with paracoccidioidomycosis mimicking inflammatory bowel disease and to systematically review available cases of the intestinal presentation of this infectious disease. Case report: Female patient, 32-years old, previously asymptomatic, presenting with acute pain in the lower right abdomen, associated with signs of peritoneal irritation and abdominal distension. Urgent surgery was performed, which identified a severe suppurative perforated ileitis. The anatomopathological study revealed fungal structures shaped as a ship's pilot wheel in Grocott-Gomori's staining, suggestive of Paracoccidioides spp. Methods: Studies were retrieved based on Medical Subject Headings and Health Sciences Descriptors, which were combined using Boolean operators. Searches were run on the electronic databases Scopus, Web of Science, MEDLINE (PubMed), BIREME (Biblioteca Regional de Medicina), LILACS (Latin American and Caribbean Health Sciences Literature), SciELO (Scientific Electronic Library Online), Embase, and Opengray.eu. Languages were restricted to English, Spanish and Portuguese. There was no date of publication restrictions. The reference lists of the studies retrieved were searched manually. Simple descriptive analysis was used to summarize the results. Results: Our search strategy retrieved 581 references. In the final analysis, 34 references were included, with a total of 46 case reports. The most common clinical finding was abdominal pain and weight loss present in 31 (67.3%) patients. Most patients were treated with itraconazole (41.3%) and amphotericin B (36.9%). All-cause mortality was 12.8%. Conclusions: Paracoccidioidomycosis should be suspected in endemics areas, specially as a differential diagnosis for inflammatory bowel disease. Endoscopic tests and biopsy are useful for diagnosis and treatment with antifungal drugs seem to be the first treatment option to achieve a significant success rate.

Effects of Arsenic Disulfide Combined with Itraconazole on Proli- feration and Apoptosis and Hedgehog Pathway of Diffuse Large B-Cell Lymphoma Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of arsenic disulfide (AS@*METHODS@#The human DLBCL cell OCI-LY3 was treated with different concentrations of AS@*RESULTS@#The DLBCL cell viability was decreased significantly at 24, 48 or 72 h as cultured with itraconazole. Along with the increasing of itraconazole concentration, the DLBCL cell viability was significantly reduced as compared with that in control group, and the results showed statistically significant(r=-0.690，r=-0.639, r=-0.833, r=-0.808, r=-0.578). The inhibitory and apoptosis rates of the cells were significantly increased as compared with those of the single drug-treated group after treated by the combination of itraconazole and AS@*CONCLUSION@#Itraconazole can inhibit proliferation of DLBCL cells in a concentration-and time-dependent manner. In addition, the combination of AS

Evaluación de susceptibilidad en cándidas spp por colorimetría obtenida en gestantes de un hospital obstétrico / Susceptibility evaluation in candida spp by colorimetry obtained in pregnant women from an obstetric hospital / Avaliação da suscetibilidade em cândida spp por colorimetria obtida em gestantes de um hospital obstétrico

INTRODUCCIÓN: las infecciones fúngicas ocasionadas por levaduras del género Cándida son extremadamente comunes en mujeres de edad reproductiva, y constituyen un motivo de atención medica de salud. OBJETIVO: evaluar la susceptibilidad de Cándidas spp, mediante el método colorimétrico (Integral Yeast System Plus). MÉTODO: fue de tipo descriptivo, transversal; se recopiló información mediante observación directa en campo y el análisis documental para obtener información bibliográfica de tipo secundaria. RESULTADOS: de los 72 casos encontrados de Cándida Albicans revela que son susceptibles a la anfotericina B (2ug/ml); de los 5 casos encontrados de Cándida Krusei revela que son sensibles a la Anfotericina B (2ug/ml); De 1 caso encontrado de Cándida Parapsilosis revela sensibilidad en la Nistatina (1.25ug/ml). En este estudio la prevalencia de la infección por Cándida fue del (44.98%). CONCLUSIONES: Cándida Albicans fue la especie más común aislada en las mujeres embarazadas representando un 72%, En la evaluación de la susceptibilidad a través del kit Integral System Yeast Plus se obtuvo que Cándida Albicans es susceptible a Anfotericina B, Flucitosina entre otros, en Cándida Glabrata se obtuvo que es sensible a la Nistatina, Anfotericina B, susceptible entre otros, en Cándida Krusei se obtuvo que es sensible a la Anfotericina B, Clotrimazol, Miconazol, susceptibles a la Nistatina, Voriconazol y resistente a la Flucitosina, Ketoconazol, Itraconazol y Fluconazol.

INTRODUCTION: fungal infections caused by yeast of the genus Candida are extremely common in women of reproductive age, and constitute a reason for medical health care. OBJECTIVE: to evaluate the susceptibility of Candida spp, using the colorimetric method (Integral Yeast System Plus). METHOD: it was descriptive, transversal; Information was collected through direct observation in the field and documentary analysis to obtain secondary bibliographic information. RESULTS: of the 72 cases found, Candida Albicans reveals that they are susceptible to amphotericin B (2ug / ml); of the 5 cases found, Candida Krusei reveals that they are sensitive to Amphotericin B (2ug / ml); Of 1 case found of Candida Parapsilosis reveals sensitivity in Nystatin (1.25ug / ml). In this study, the prevalence of Candida infection was (44.98%). CONCLUSIONS: Candida Albicans was the most common species isolated in pregnant women, representing 72%. In the evaluation of susceptibility through the Integral System Yeast Plus kit it was obtained that Candida Albicans is susceptible to Amphotericin B, Flucytosine among others, in Candida Glabrata was obtained that it is sensitive to Nystatin, Amphotericin B, susceptible among others, in Candida Krusei it was obtained that it is sensitive to Amphotericin B, Clotrimazole, Miconazole, susceptible to Nystatin, Voriconazole and resistant to Flucytosin, Ketoconazole, Itraconazole and Fluconazole.

INTRODUÇÃO: as infecções fúngicas causadas por leveduras do gênero Candida são extremamente comuns em mulheres em idade reprodutiva e constituem motivo de cuidados médicos. OBJETIVO: avaliar a suscetibilidade de Candida spp, por meio do método colorimétrico (Integral Yeast System Plus). MÉTODO: foi descritivo, transversal; as informações foram coletadas por meio de observação direta em campo e análise documental para obtenção de informações bibliográficas secundárias. RESULTADOS: Dos 72 casos encontrados, Cândida Albicans revelou ser suscetíveis à anfotericina B (2ug /ml); dos 5 casos encontrados, Candida Krusei revela que são sensíveis à Anfotericina B (2ug / ml); de 1 caso encontrado de Candida Parapsilosis revela sensibilidade na Nistatina (1,25ug / ml). Neste estudo, a prevalência de infecção por Candida foi (44,98%). CONCLUSÕES: Cândida Albicans foi a espécie mais comum isolada em gestantes, representando 72%. Na avaliação da susceptibilidade através do kit Integral System Yeast Plus foi obtido que Candida Albicans é suscetível à Anfotericina B, Flucitosina entre outras, em Cândida Glabrata foi obtido que é sensível a Nistatina, Anfotericina B, suscetível entre outras, em Candida Krusei foi obtido que é sensível a Anfotericina B, Clotrimazol, Miconazol, suscetível a Nistatina, Voriconazol e resistente a Flucitosina, Cetoconazol, Itraconazol e Fluconazol.

Paracoccidioidomycosis: an uncommon clinical presentation

Abstract Paracoccidoiomycosis is a systemic mycosis with a higher incidence in males with history of exposure to the rural environment; its classic clinical manifestation is an oro-pulmonary lesion. The authors report a case of a female, urban, 76-year-old patient with atypical clinical-dermatological presentation and diagnostic conclusion after histopathological examination. The clinical response was quick and complete after treatment with itraconazole 400 mg/day in the first month, decreased to 200 mg/day until the sixth month of treatment.

Esporotricose felina: um relato de caso de disseminação cutânea e sistêmica em gato negativo para FIV e FeLV / Feline sporotrichosis: a case report of cutaneous and systemic dissemination in cat negative for FIV and FeLV

A esporotricose é uma zoonose causada por fungos do gênero Sporothrix. Os gatos doentes têm importante potencial zoonótico e frequentemente revelam uma apresentação disseminada da doença. O objetivo deste relato de caso é descrever as características clínicas e anatomopatológicas de um caso de esporotricose felina refratária ao tratamento com apresentação clínica cutânea disseminada e sistêmica. Um felino macho de 3 anos de idade foi tratado para esporotricose com itraconazol e obteve resolução completa das lesões cutâneas. Porém, um ano após alta clínica, o animal apresentou aumento e ulceração da região nasal. Após cultura fúngica positiva para Sporothrix spp foi instituído tratamento com itraconazol 100mg associado ao iodeto de potássio 20mg por via oral diariamente e transcorrido 3 meses de tratamento, foi observada piora progressiva do sinais clínicos com disseminação de lesões para outras regiões do corpo. O animal foi submetido à eutanásia e encaminhado para necrópsia no Serviço de Anatomia Patológica da Faculdade de Veterinária da Universidade Federal Fluminense. Amostras da língua, pulmão, fígado, baço, rim, cérebro, linfonodo e pele foram coletadas para evidência de disseminação do agente fúngico e avaliação de alterações microscópicas. A coloração de metenamina de prata de Grocott foi utilizada para facilitar a visualização de leveduras sugestivas de Sporothrix spp nos cortes histológicos. Leveduras foram visualizadas em amostras de pele, língua, linfonodo, rim, fígado, baço e cérebro. No presente relato a disseminação do Sporothrixspp para diversos órgãos sinaliza a necessidade de uma minuciosa investigação dos casos graves de esporotricose felina para o tratamento adequado.

Sporotrichosis is a zoonosis caused by fungi of the genus Sporothrix. Sick cats have an significant zoonotic potential and often show a widespread presentation of the disease. The purpose of this case report is to describe the clinical and anatomopathological characteristics of a case of feline sporotrichosis refractory to treatment with disseminated and systemic cutaneous clinical presentation. A 3-year-old male feline was treated for sporotrichosis with itraconazole and achieved complete resolution of the skin lesions. However, one year after clinical discharge, the animal presented an increase and ulceration of the nasal region. After a positive fungal culture for Sporothrix spp, treatment with itraconazole 100mg associated with potassium iodide 20mg was instituted orally daily and after 3 months of treatment, a progressive worsening of the symptoms was observed with the spread of lesions to other regions of the body. The animal was euthanized and sent for necropsy at the Pathological Anatomy Service of the Veterinary Faculty of Universidade Federal Fluminense. Samples of the tongue, lung, liver, spleen, kidney, brain, lymph node, and skin were collected for evidence of spread of the fungal agent and evaluation of microscopic changes. Grocott silver methenamine staining was used to facilitate the visualization of yeasts suggestive of Sporothrix spp in histological sections. Yeasts were visualized in samples of skin, tongue, lymph node, kidney, liver, spleen, and brain. In the present report, the spread of Sporothrix spp to different organs signals the need for a thorough investigation of severe cases of feline sporotrichosis for the proper treatment.

Case for diagnosis. Pruritic erythematosquamous lesion in the auricle

Abstract Chromoblastomycosis is a subcutaneous mycosis with chronic evolution that mainly affects the lower limbs and, less frequently, the auricles. Clinically, it presents with papillary verrucous, nodular, and/or tumoral lesions, whether isolated or infiltrated, forming plaques and, sometimes, atrophic in some areas. Histopathologically, it is characterized by a dermal granulomatous inflammatory infiltrate, and the diagnosis can be confirmed by the presence of fumagoid bodies in anatomopathological or direct mycological exams. The treatment to be indicated will depend on the extent and location of the lesions, using systemic antifungals, surgical removal, cryotherapy, thermotherapy, and immunoadjuvants. The present study reports an atypical presentation of chromoblastomycosis on the auricle.

Azoles de antes y ahora: una revisión / Azoles of then and now: a review

Resumen Los azoles son fármacos que inhiben la enzima 14α-esteroldemetilasa, impidiendo la unión de ergosterol; esto altera la estructura y función de la pared celular fúngica. Especialmente el grupo de los triazoles: fluconazol, itraconazol, voriconazol, posaconazol e isavuconazol, son una alternativa farmacológica para el tratamiento de la enfermedad fúngica invasora causada por Aspergillus spp, Candida spp, Cryptococcus spp, patógenos emergentes como los Mucorales, y de micosis endémicas como las ocasionadas por Histoplasma spp y Coccidioides spp. Los efectos adversos de los triazoles son menos frecuentes comparados con los ocasionados por anfotericina B, un antifúngico de uso común para estas micosis. Los principales efectos adversos de los triazoles son hepáticos, gastrointestinales y cardiovasculares como la prolongación del intervalo QT. Las interacciones farmacológicas son usuales y se presentan con moléculas que usan sustratos del citocromo CYP3A4, lo que incluye anti-retrovirales, anti-tuberculosos e inmunomoduladores. En este trabajo se revisan la historia, características farmacológicas y los ensayos clínicos que evidencian su eficacia clínica en los diferentes escenarios clínicos.

Abstract The azoles are drugs that inhibit the 14α-sterol-demethylase enzyme preventing the binding of ergosterol, altering the functionality and structure of the fungal cell wall. Especially the group of triazoles: fluconazole, itraconazole, voriconazole, posaconazole and isavuconazole, are a pharmacological alternative for the treatment of the invasive fungal disease, caused by Aspergillus spp, Candida spp, Cryptococcus spp, by emerging pathogens for example, the Mucoral and finally of endemic mycosis as those caused by Histoplasma spp. and Coccidioides spp. The adverse effects of the triazoles are less frequent compared to those caused by amphotericin B, the main ones being hepatics, gastrointestinals and cardiovasculars, such as the prolongation of the QT interval. The pharmacological interactions are common and occur with molecules that use the substrates of the CYP3A4 cytochrome, for example: antiretroviral, anti-tuberculous and immunomodulators. The history, pharmacological characteristics and clinical trials are reviewed.

Fatores de virulência e susceptibilidade a antifúngicos de Cryptococcus Spp / Virulence factors and susceptibility to Cryptococcus Spp. antifungals

Criptococose é uma doença grave que afeta tanto imunocomprometidos quanto imunocompetentes, com isso analisar a virulência é fundamental para novas terapêuticas. Objetivo: Analisar a capacidade de virulência e susceptibilidade aos antifúngicos de Cryptococcus spp. isolados de líquor de pacientes de hospital do norte do Paraná. Métodos: A partir de dois isolados clínicos C. neoformans e C. gattii, realizou-se a confirmação da identificação. Para a virulência, avaliou-se o tamanho da cápsula, capacidade de sobrevivência após exposição a neutrófilos, produção de melanina e urease. No antifungigrama por difusão em disco utilizou-se: anfotericina B, cetoconazol, voriconazol, itraconazol e miconazol. Resultados: C. gattii destaca-se por maior desenvolvimento da cápsula além da melhor capacidade de sobreviver a fagocitose em relação ao C. neoformans. No antifungigrama, ambos os isolados se apresentam sensíveis às drogas estudadas. Conclusão: Esses achados contribuem para a compreensão das diferentes patogêneses entre C. gattii e C. neoformans.

Cryptococcosis is a serious disease that can affect both immunocompromised and immunocompetent individuals, thus the virulence analysis is fundamental for the development of new treatments. Objective: To analyze the virulence and susceptibility of Cryptococcus spp. isolated from cerebrospinal fluid of patients from a hospital in the north of Paraná. Methods: From two clinical isolates, C. neoformans and C. gattii were confirmed and identified. For virulence, capsule size, survival capacity after exposure to neutrophils, melanin production and urease were evaluated. In the disc-diffusion method, the following antifungals were used: amphotericin B, ketoconazole, voriconazole, itraconazole and miconazole Results: It was observed that C. gattii presents greater results for development of the capsule beside presenting the best ability to survive phagocytosis in relation to C. neoformans. In the disc-diffusion method, both isolates presented sensitivity to the studied drugs. Conclusion: These findings contribute to the understanding of the different pathogens between C. gattii and C. neoformans.

Therapeutic failure with itraconazole in sporotrichosis due to bariatric surgery

Abstract Sporotrichosis is a deep mycosis of subacute or chronic evolution, caused by the dimorphic fungus of the genus Sporothrix. The treatment is carried out with antifungal orally or intravenously. Therapeutic success can be affected by several factors, such as altered gastrointestinal physiology by surgery. More and more patients are submitted to bariatric surgeries and the literature for the alterations of the absorption of medications in this context is very scarce. We intend to contribute to a better understanding with this case report of cutaneous-lymphatic sporotrichosis in a patient after bariatric surgery without response to itraconazole treatment, even at high doses.

Synergistic effect of ibuprofen with itraconazole and fluconazole against Cryptococcus neoformans

The present study investigated the association of the non-steroidal anti-inflammatory drug ibuprofen with itraconazole, fluconazole and amphotericin B against Cryptococcus neoformans isolates. The minimal inhibitory concentration (MIC) was found according to M27-A3 protocol and in vitro interactions were evaluated using checkerboard microdilution method. Synergism was demonstrated between azoles and ibuprofen for most isolates. However, no synergistic effects were seen when amphotericin B was combined with ibuprofen. Therefore, our results suggest that ibuprofen presents clinical potential when combined with azole drugs in the treatment of cryptococcosis.

Coccidioidomycosis in a reference center in Northeast Brazil: clinical/epidemiological profile and most common radiological findings

Abstract INTRODUCTION: Coccidioidomycosis, a disease caused by Coccidioides immitis or Coccidioides posadasii, is endemic in arid climatic regions in Northeast Brazil. Its prevalence is higher among young adult males living in rural areas. Existing literature about this disease in Ceará, a Northeast Brazilian state, are scarce. Here, we aimed to outline the clinical and epidemiological profiles, radiological patterns, and therapeutic responses of patients with coccidioidomycosis in a reference center in Ceará, Brazil. METHODS This is a descriptive study with quantitative analysis. Patients who underwent medical follow-up in São José Hospital of Infectious Diseases and received confirmed mycological diagnosis of coccidioidomycosis between January, 2007 and December 2017 were included. Epidemiological, clinical, radiological, and therapeutic response data were collected from medical charts. RESULTS Thirty patients were included. The patients were males with median age of 30 years, and 73% were considered to have high-risk exposure to Coccidioides owing to professional activities. Cough (96.7%), dyspnea (63.3%), fever (86.7%), and pleuritic pain (60%) were the most prevalent clinical manifestations. Interstitial pattern (91.3%) was the most frequent pulmonary radiological finding. Fluconazole, amphotericin B, and itraconazole were administered for treatment (in 82.1%, 42.8%, and 21.4% of cases, respectively). A favorable outcome was observed in 83.8% of patients. CONCLUSIONS Coccidioidomycosis was more prevalent in the central and southern regions of the State of Ceará. Understanding the local epidemiology and clinical manifestations of the disease, in addition to the pulmonary radiologic findings, may aid the early detection of coccidioidomycosis and facilitate early diagnosis.

Subcutaneous zygomycosis due to Basidiobolus ranarum in a Filipino child responding to itraconazole: A case report

@# Introduction: Subcutaneous zygomycosis or basidiobolomycosis is caused by a saprophytic fungi Basidiobolus ranarum (B. ranarum). It presents clinically as a slowly growing painless subcutaneous nodule more commonly on the extremity, trunk and rarely on other parts of the body. Mode of infection has not been established but most likely follows traumatic implantation. We report a gradually evolving case of basidiobolomycosis in a 12-year-old immunocompetent Filipino male with no history of trauma who responded dramatically to itraconazole. Case summary: Subcutaneous zygomycosis is caused by Basidiobolus ranarum (B. ranarum) which is endemic in parts of Africa, India and other parts of Asia. We report an evolving case of a Filipino male child who presented with chronic and persistent subcutaneous nodules and plaques on the left extremity. Dense cell infiltrates consisting of lymphocytes, histiocytes and eosinophils were seen on histology with non-septated hyphal structures on Gomori’s methenamine silver stain. Fungal culture of the lesion yielded B. ranarum. Complete resolution of the lesions were observed after 6 months of itraconazole therapy alone. Conclusion: This case demonstrated the gradual progression of the disease, and that the lack of a history of trauma does not exclude its diagnosis. Subcutaneous zygomycosis should be highly suspected in chronic painless subcutaneous nodules with swelling, and its early recognition is crucial to prevent progression of the disease. In patients whom an infectious cause is suspected, appropriate cultures, special staining, and sometimes repeat biopsies of new cutaneous lesions may be helpful in determining or ruling out the associated disease. Furthermore, performing PAS stain alone to identify the presence or absence of a fungi is insufficient, rather, additional staining such as GMS should be done to heighten detection of fungal elements.