Fungal keratitis management in a referral cornea center in Brazil / Manejo de ceratites fúngicas em centro de referência no Brasil

Abstract Purpose: To report etiological diagnosis, predisposing risk factors, therapeutic strategies and visual outcome of patients treated at the Department of Ophthalmology of Federal University of São Paulo. Methods: This is a retrospective, descriptive, and observational study from medical and laboratory records of the Department of Ophthalmology of Federal University of São Paulo, including all patients with culture proven fungal keratitis in 5 years, from October 2012 through October 2017. Results: There were 2260 fungi microbiologic test requests. Of these, 140 samples had positive cultures for fungi and sixty-six patients were followed at our clinic. Forty-five patients (68.2%) were men, and the mean age was 48.06 (±17.39) years. Fusarium spp. was the most frequently isolated fungus (32 cases; 48.5%), followed by Candida parapsilosis (12 cases; 18.2%). Thirty-four patients (51.5%) underwent intracameral injection of amphotericin B (5 µg per 0.1 ml). In 11 patients (32.3%), infection was eradicated after intracameral amphotericin B associated to topical antifungal treatment and, in 23 patients (67.7%), therapeutic keratoplasty was needed. No complication related to intracameral amphotericin B injection was observed in this series. Forty-three patients (65.1%) ended up with therapeutic keratoplasty. Three patients (4.5%) evolved to evisceration or enucleation. At the last follow-up visit, 53 patients (80.3%) had visual acuity worse than 20/200. Conclusion: Despite current antifungals drugs and distinct administration strategies, fungal keratitis remains challenging. Delayed antifungal therapy may explain poor clinical outcomes. Intracameral amphotericin B associated to topical antfungal treatment seems to be a safe and helpful alternative for non-responsive fungal keratitis. But it is important to formulate other treatment strategies, hence to improve patients' outcomes, since most patients ended-up with significant visual impairment even after current treatment.

Resumo Objetivo: Descrever diagnósticos etiológicos, fatores de risco, estratégias terapêuticas e resultados visuais de pacientes com ceratite fúngica tratados no Departamento de Oftalmologia da Universidade Federal de São Paulo. Métodos: Trata-se de um estudo retrospectivo, descritivo e observacional, a partir da análise de prontuários médicos e laboratoriais do Departamento de Oftalmologia da Universidade Federal de São Paulo, incluindo todos os pacientes com ceratite fúngica comprovada por cultura no período de outubro de 2012 a outubro de 2017. Resultados: Foram realizadas 2260 solicitações de testes microbiológicos. Destas, 140 amostras apresentaram culturas positivas para fungos, e 66 pacientes foram acompanhados em nosso serviço. Quarenta e cinco pacientes (68,2%) eram do sexo masculino, e a média de idade foi de 48,06 (± 17,39) anos. Fusarium spp. foi o fungo mais freqüentemente isolado (32 casos; 48,5%), seguido por Candida parapsilosis (12 casos; 18,2%). Trinta e quatro pacientes (51,5%) foram submetidos à injeção intracameral de anfotericina B (5 µg por 0,1 ml). Destes, 11 pacientes (32,3%) tiveram a infecção erradicada. Nos outros 23 pacientes (67,7%), o transplante terapêutico foi necessário. Nenhuma complicação relacionada à injeção intracameral de anfotericina B foi observada neste estudo. No total, 43 pacientes (65,1%) evoluíram para transplante terapêutico, e 3 pacientes (4,5%) foram submetidos à evisceração ou enucleação. Cinquenta e três pacientes (80,3%) apresentaram acuidade visual final pior que 20/200. Conclusões: Apesar dos diversos medicamentos antifúngicos atuais e vias de administração, o tratamento das ceratites fúngicas permanece desafiador. O atraso no início do tratamento adequado pode justificar o desfecho clínico desfavorável de grande parte dos pacientes. A injeção intracameral de anfotericina B mostrou-se uma alternativa terapêutica segura para ceratites fúngicas refratárias. Mas outras estratégias de tratamento devem ser formuladas, visando melhorar os resultados visuais dos pacientes.

Infectious keratitis in southern Brazil: a comparison culture negative and culture positive patients / Ceratite infecciosa no sul do Brasil: comparação entre pacientes com cultura negativa e positiva

Abstract Purpose: To compare clinical-epidemiological profile and treatment outcome between culture negative and culture positive keratitis patients. Methods: Patients with suspected infectious keratitis seen at two ophthalmic hospitals in Curitiba, Brazil, between June 2014 and April 2016, were prospectively studied. Ophthalmological exam with corneal scraping and microbiological tests were performed. Data regarding follow up, surgical interventions and treatment outcome were collected after 12 weeks of the first visit trough medical chart review. From the results of the culture, two groups were formed: culture negative keratitis (CNK) and culture positive keratitis (CPK). Results: According to inclusion criteria 21 patients were classified as culture negative keratitis and 20 patients as culture positive keratitis. The number of patients on antibiotic drops at the first visit was greater in CNK group (90.5% versus 60%; p=0.032). Surgical procedures were necessary in 3 patients (15%) in CNK group and in 7 patients (36,8%) in CPK group (p=0.155). Treatment success was achieved by 85% (17/20) of the patients in CNK group and by 61% (11/18) of the patients in CPK group (p=0.144). There was no significant difference between groups regarding age, gender, place of residence, presence of comorbidities, risk factors for infectious keratitis, duration of symptoms and characteristics of corneal ulcer. Conclusions: Previous treatment with antibiotics correlates with negative culture results. There was no significant difference in treatment outcome between culture negative and culture positive keratitis patients.

Resumo Objetivo: Comparar os perfis clinico-epidemiológicos e os desfechos entre pacientes com ceratite com cultura positiva e pacientes com ceratite com cultura negativa. Métodos: Pacientes com ceratite infecciosa, atendidos em dois hospitais oftalmológicos em Curitiba, Brasil, entre junho de 2014 e abril de 2016, foram estudados prospectivamente. Exame oftalmológico, raspado de córnea e exames microbiológicos foram realizados no primeiro atendimento. Os dados quanto a seguimento e desfecho foram coletados após 12 semanas do primeiro atendimento através de revisão de prontuário. A partir dos resultados das culturas, dois grupos foram formados: ceratite com cultura negativa e ceratite com cultura positiva. Resultados: Vinte e um pacientes foram classificados como ceratite com cultura negativa e 20 como ceratite com cultura positiva. O número de pacientes em uso de colírio antibiótico no primeiro atendimento foi maior no grupo de cultura negativa (90,5% versus 60%; p=0,032). Sete pacientes (37%) no grupo cultura positiva precisaram de procedimentos cirúrgicos no manejo da ceratite, versus 3 pacientes (15%) do grupo cultura negativa (p=0,155). Oitenta e cinco por cento (17/20) dos pacientes do grupo cultura negativa alcançaram sucesso no tratamento, contra 61% (11/18) dos pacientes no grupo cultura positiva (p=0,144). Não houve diferença entre os grupos quanto a idade, gênero, local de procedência, presença de comorbidades, fatores de risco, duração dos sintomas e características da úlcera de córnea. Conclusão: Tratamento prévio com colírio de antibiótico correlaciona-se com resultados negativos de cultura. Não houve diferença no desfecho após tratamento entre os pacientes com cultura negativa e cultura positiva.

Características clínico-epidemiológicas y evolución del tratamiento en pacientes con úlceras corneales / Clinical-epidemiological characteristics and treatment evolution of patients with corneal ulcer

Las úlceras corneales de origen infeccioso son una emergencia oftalmológica que amenaza la visión y la integridad estructural del ojo, causando ceguera en 1,5 a 2 millones de casos al año por lo que requiere tratamiento inmediato. El objetivo fue determinar el patrón epidemiológico, factores de riesgo y efectividad del tratamiento en pacientes con úlcera corneal en la Fundación Visión en el periodo 2015-2017. Estudio de cohorte prospectivo donde se evaluó 53 pacientes con úlcera corneal de causa infecciosa que consultaron en la Fundación Visión en el periodo 2015-2017, y tuvieron un seguimiento mínimo de 4 meses. Se encontró un predominio del sexo masculino (69,8%), edad 45-65 años (49,1%), casados (54,7%), de condición socioeconómica baja (56,6%), agricultores (26,4%), con antecedente de traumatismo corneal (69,8%) o uso de lentes de contacto (17%). El agente etiológico fue bacteriano en el 49,1% y micótico en el 37,7%; para los de origen bacteriano el tratamiento más empleado fueron colirios fortificados de Cefazolina + Gentamicina y Natamicina/Fluconazol en caso de ser micótico. La evolución fue favorable en 90,9% y 80,0% de los bacterianos y micóticos, respectivamente. Los grupos de riesgo detectados fueron pacientes varones, agricultores, de condición socioeconómica baja, con antecedente de traumatismo corneal o uso de lentes de contacto. La efectividad del tratamiento utilizado fue mayor al 80%, siendo en su mayoría patógenos bacterianos(AU)

Correlation between pathogenic species and clinical findings, disease severity, and visual outcome in patients with fungal keratitis / Correlação entre espécies patogênicas e achados clínicos, gravidade da doença e desfecho visual em pacientes com ceratite fúngica

ABSTRACT Purpose: To determine whether a correlation exists between pathogenic species and clinical findings, disease severity, and visual outcome in patients with keratitis and fungal growth in microbiological culture. Methods: A retrospective study of patients with fungal growth in the microbiological culture of corneal scrapings. Patients were treated at an ophthalmologic reference center in Southeastern Brazil from January 1992 to October 2015. Results: Medical records of 181 patients (131 males and 50 females) with a mean age of 47 ± 18 years were analyzed. The three most common etiologies were Fusarium sp. (38.7%), Aspergillus sp. (15%), and Candida sp. (13.2%). Among these, Fusarium sp. was the most frequent in patients aged £50 years (p=0.002) and in those with a recent history of a foreign body and/or ocular trauma (p=0.01). Candida sp. was the most frequent etiology in patients aged >50 years (p=0.002), in those with postoperative ocular surgery (p=0.002); in those with a previous ocular pathology (p=0.0007); and in immunodepressed patients (p=0.0004). Conclusion: Fusarium sp. was predominant in patients aged £50 years and those with a recent history of foreign body and/or ocular trauma, whereas Candida sp. was predominant in older adults, in those with a postoperative ocular surgery, in those with a previous ocular pathology, and in immunodepressed patients.

RESUMO Objetivo: Determinar se existe uma correlação entre espécies patogênicas e achados clínicos, gravidade da doença e resultado visual em pacientes com ceratite e crescimento de fungos em cultura microbiológica. Métodos: Estudo retrospectivo de pacientes com crescimento de fungos na cultura microbiológica de raspado de córnea. Os pacientes foram tratados em um centro de referência oftalmológica no Sudeste do Brasil de janeiro de 1992 a outubro de 2015. Resultados: Foram analisados registros médicos de 181 pacientes (131 homens e 50 mulheres) com idade média de 47 ± 18 anos. As três etiologias mais comuns foram Fusarium sp. (38,7%), Aspergillus sp. (15%) e Candida sp. (13,2%). Entre estas, Fusarium sp. foi a mais frequente em pacientes com idade £50 anos (p=0,002) e naqueles com história recente de corpo estranho e/ou trauma ocular (p=0,01). Candida sp. foi a etiologia mais frequente em pacientes com idade >50 anos (p=0,002), naqueles com cirurgia ocular pós-operatória (p=0,002); naqueles com patologia ocular prévia (p=0,0007); e em pacientes imunodeprimidos (p=0,0004). Conclusão: Fusarium sp. foi predominante em pacientes com idade £50 anos e naqueles com história recente de corpo estranho e/ou trauma ocular; enquanto Candida sp. foi predominante em adultos mais velhos, naqueles com cirurgia ocular pós-operatória, naqueles com patologia ocular prévia e em pacientes imunodeprimidos.

Treatment compliance of patients with paracoccidioidomycosis in Central-West Brazil / Adesão ao tratamento de pacientes com paracoccidioidomicose na Região Centro-Oeste do Brasil

ABSTRACT Objective: To evaluate the treatment compliance of patients with paracoccidioidomycosis. Methods: We studied 188 patients with paracoccidioidomycosis admitted to a tertiary referral hospital in the Central-West Region of Brazil from 2000 to 2010, to assess their compliance to treatment. In order to be considered compliant, patients needed to present two established criteria: (1) receive medicines from the pharmacy, and (2) achieve a self-reported utilization of at least 80% of the dispensed antifungal compounds prescribed since their previous appointment. Results: Most patients were male (95.7%), had the chronic form of the disease (94.2%), and were treated with cotrimoxazole (86.2%). Only 44.6% of patients were treatment compliant. The highest loss to follow-up was observed in the first 4 months of treatment (p < 0.02). Treatment compliance was higher for patients with than for those without pulmonary involvement (OR: 2.986; 95%CI 1.351-6.599), and higher for patients with than without tuberculosis as co-morbidity (OR: 2.763; 95%CI 1.004-7.604). Conclusions: Compliance to paracoccidioidomycosis treatment was low, and the period with the highest loss to follow-up corresponds to the first four months. Pulmonary paracoccidioidal involvement or tuberculosis comorbidity predicts a higher compliance to paracoccidioidomycosis therapy.

RESUMO Objetivo: Avaliar a adesão ao tratamento de paracoccidioidomicose. Métodos: Estudo conduzido com 188 pacientes com paracoccidioidomicose atendidos em um hospital terciário na Região Centro-Oeste do Brasil, de 2000 a 2010, para avaliar adesão ao tratamento. Foram considerados aderentes pacientes que tiveram o seguinte critério: retiraram os medicamentos na farmácia e autorrelataram a utilização de, no mínimo, 80% de dispensação dos antifúngicos prescritos na última consulta. Resultados: A maioria dos pacientes era homem (95,7%), tinha a forma crônica da doença (94,2%) e foi tratada com sulfametoxazol/trimetropim (86,2%). Apenas 44,6% dos pacientes aderiram ao tratamento. A maior perda de seguimento foi observada nos primeiros 4 meses de tratamento (p < 0,02). Adesão ao tratamento foi maior em pacientes com do que sem envolvimento pulmonar (RC: 2,986; IC95% 1,351-6,6599) e maior para os pacientes com do que sem tuberculose associada (RC 2,763; IC95% 1,004-7,604). Conclusões: A adesão ao tratamento da paracoccidioidomicose foi baixa e os primeiros 4 meses constituíram o período com maior evasão. Pacientes com envolvimento paracocidióidico pulmonar ou tuberculose associada revelaram maior adesão ao tratamento da paracoccidioidomicose.

Histoplasmosis diseminada como manifestación inicial del linfoma linfocítico de células pequeñas / Disseminated histoplasmosis as a first clinical manifestation in a patient with small lymphocytic lymphoma: A case report

RESUMEN El linfoma linfocítico de células pequeñas es una neoplasia de células B maduras con un amplio espectro de presentaciones clínicas. Las infecciones por gérmenes oportunistas no asociadas con el tratamiento, incluso en estadios avanzados de la enfermedad, tienen baja incidencia. Se han reportado muy pocos casos de pacientes con linfoma linfocítico de células pequeñas asociado a histoplasmosis diseminada que no habían recibido quimioterapia en el momento del diagnóstico. Se presenta el caso de una paciente de 82 años que fue hospitalizada por presentar tos seca intermitente, astenia y adinamia de un mes de evolución. Se le practicaron múltiples estudios para detectar infecciones o compromiso inmunológico o reumático, y se diagnosticó un síndrome adenopático extenso con compromiso cervical, torácico y retroperitoneal. En la citometría de flujo y en la biopsia de ganglio linfático cervical, se reportaron los fenotipos CD19+, CD20dim, CD5+, CD45+, CD23+, CD43neg y CD10neg, con restricción de la cadena ligera kappa, lo cual confirmó un linfoma linfocítico de células pequeñas. En la histopatología del ganglio, se observaron granulomas epitelioides sin necrosis, pero las coloraciones especiales no mostraron la presencia de microorganismos, en tanto que el cultivo del ganglio fue positivo para Histoplasma capsulatum. Se inició el tratamiento antifúngico con anfotericina B e itraconazol, y la paciente tuvo una adecuada evolución. Dado que no se cumplían los criterios para el tratamiento oncológico, se continuó con su observación mediante controles periódicos. Las infecciones oportunistas pueden ser la manifestación clínica inicial en pacientes con síndromes linfoproliferativos de bajo grado. Este caso demuestra que pueden desarrollarse, incluso, en ausencia de quimioterapia.

ABSTRACT The small lymphocytic lymphoma is a mature B cell neoplasm with a broad spectrum of clinical presentations. Opportunistic infections that are not related to the treatment, even in advanced stages, have a low incidence rate. There are few case reports in the medical literature of patients who have not received immunosuppressive therapy and present with small lymphocytic lymphoma associated with disseminated histoplasmosis at diagnosis. A female 82-year-old patient was admitted due to an intermittent dry cough, asthenia, and adynamia that had persisted for one month. Multiple studies to detect infections and immuno-rheumatic conditions were performed and an extensive cervical, thoracic and peritoneal adenopathic syndrome was diagnosed. A flow cytometry and a cervical lymph node biopsy were performed reporting CD19+, CD20dim, CD5+, CD45+, CD23+, CD43neg, and CD10neg phenotypes with restriction in the light kappa chain compatible with a small lymphocytic lymphoma. Epithelioid granulomas without necrosis were observed in the lymph node histopathology and special colorations showed no microorganisms. The culture from the lymph node was positive for Histoplasma capsulatum. We initiated treatment with amphotericin B and itraconazole with an adequate response. In the absence of compliance with oncology treatment criteria, the patient was managed on a "watch and wait" basis. Opportunistic infections could be the initial clinical manifestation in patients with low-grade lymphoproliferative syndromes. This case report shows that they can develop even in the absence of chemotherapy.

Esporotricosis del pabellón auricular: comunicación de un caso atípico simulando una celulitis bacteriana / Auricular sporotrichosis: atypical case report simulating bacterial cellulitis

Resumen La esporotricosis es la micosis subcutánea o por implantación más frecuente en México. Se comunica el caso de una esporotricosis cutánea-fija preauricular que simuló una celulitis bacteriana atípica, en una paciente anciana sin antecedente de traumatismo. La biopsia mostró un granuloma supurativo con presencia de levaduras escasas. En el cultivo se identificó Sporothrix schenckii que se confirmó por biología molecular. Se trató con itraconazol obteniéndose una curación clínica y micológica. Se presenta el caso de presentación atípica, proveniente de una zona semidesértica con clima extremo.

Sporotrichosis is the most common subcutaneous or implantation mycosis in Mexico. The case of a preauricular cutaneous-fixed sporotrichosis simulating atypical bacterial cellulitis is reported in an elderly patient with no history of trauma. The biopsy showed a suppurative granuloma with scarce yeast. Sporothrix schenckii was identified in the culture and confirmed by molecular biology. She was treated with itraconazole and a clinical and mycological cure was obtained. The case of atypical presentation is presented, coming from a semi-arid zone with extreme weather.

Epidemiología, especies, resistencia antifúngica y evolución de las candidemias en un hospital universitario de Buenos Aires, Argentina, durante 16 años / Epidemiology, species, antifungal resistance and outcome of candidemia in a university hospital in Buenos Aires, Argentina for 16 years

Resumen Introducción: La epidemiologia de las candidemias varía en cada región. Objetivos: Conocer la epidemiología de las candidemias en un hospital durante 16 años. Material y Métodos: Se revisaron los episodios de candidemia ocurridos en el Hospital de Clínicas de Buenos Aires desde 01/01/98 al 31/12/13. Resultados: Se identificaron 374 episodios de candidemia. La incidencia fue de 2,21/1.000 egresos y aumentó de 1,96 (1998-2005) a 2,25 (2006-2013) (p = 0,023). Se diagnosticaron: 5,4% en neonatos, 1,7% en lactantes, 6,5% en niños mayores, 31,8% en adultos y 52,7% en adultos mayores de 64 años. Los episodios fueron causados por C. albicans (40,9%), C. parapsilosis (21,7%), C. tropicalis (15,5%), C. glabrata (13,9%), otras especies de Candida (5,1%) y candidemias multiespecies (2,9%). El 5,3% de los aislados fue resistente a fluconazol. Setenta y cuatro por ciento de los pacientes recibió tratamiento; 70,3% lo inició con fluconazol, 25% con anfotericina B desoxicolato y 4,7% con equinocandinas o anfotericinas lipídicas. Se retiró 81% de los catéteres venosos centrales. La mortalidad fue de 47,9%, pero fue de 60,8% para los adultos mayores. Conclusión: La incidencia de candidemias se incrementó a través de los años, fue mayor en los adultos mayores y esta población tuvo peor evolución.

Background: The epidemiology of candidemia vary by region. Aim: To determine the epidemiology of candidemia in a hospital for 16 years. Material and Methods: Episodes of candidemia occurred in the Hospital de Clinicas of Buenos Aires were reviewed, from 01/01/98 to 31/12/13. Results: 374 episodes of candidemia were identified. The incidence was 2.21/1,000 discharges and increased from 1.96 (1998-2005) to 2.25 (2006-2013) (p = 0.023). Candidemia was diagnosed: 5.4% in neonates, 1.7% in infants, 6.5% in children, 31.8% in adults and 52.7% in elderly adults over 64 years old. The episodes were caused by C. albicans (40.9%), C. parapsilosis (21.7%), C. tropicalis (15.5%), C. glabrata (13.9%), other species of Candida (5.1%) and more than one species of Candida (2.9%). The 5.3% of the isolates were resistant to fluconazole. 74% of patients were treated. Initial treatments were with fluconazole (70.3%), amphotericin B deoxycholate (25%), echinocandins or lipidic amphotericin (4,7%). The 81% of central venous catheters were taken off. Mortality rate was of 47.9%, but in the elderly adults was of 60.8%. Conclusion: The incidence of candidemia showed an increase over the years. It was higher in the elderly adults, being the group with worse outcomes.

Epidemiología y susceptibilidad antifúngica de especies causantes de candidemia en la ciudad de Valdivia, Chile / Epidemiology and antifungal susceptibility of species producing candidemia in Valdivia, Chile

Resumen Introducción: La epidemiología de la candidemia en Chile es poco conocida, a pesar de ser una enfermedad frecuente y grave. Objetivos: Analizar la incidencia y perfil de susceptibilidad in vitro de especies del género Candida causantes de candidemia en el Hospital Base Valdivia. Material y Métodos: Se identificó todos los casos de candidemia ocurridos en la institución entre marzo de 2009 y agosto de 2011. Se estudió la distribución de especies y susceptibilidad in vitro por el método de disco difusión. Resultados: Se estudiaron 27 episodios de candidemia. La incidencia varió de 0,3 a 0,7 por 1.000 egresos (según servicio clínico). Fueron factores de riesgo: la hospitalización, uso previo de antimicrobianos, edad avanzada y enfermedad de base (insuficiencia renal, enfermedad cardiaca y pulmonar). La especie más frecuente fue C. albicans seguida de C. tropicalis, C. glabrata y C. krusei. Voriconazol fue el antifúngico con mejor actividad in vitro y hubo resultados variables para anfotericina B, fluconazol e itraconazol. Discusión: La incidencia encontrada fue superior a la de países desarrollados. Candida albicans, constituye la especie más frecuente, con alta sensibilidad in vitro a fluconazol, debiendo ser vigiladas las especies de Candida no albicans. Es fundamental desarrollar nuevas investigaciones para detectar potenciales variaciones epidemiológicas.

Background: Candidemia disease in Chile is not very known, despite being a very common and serious disease. Aim: To analyze incidence and susceptibility profile of species from the genus Candida in Hospital Base Valdivia. Material and Methods: All candidemia cases presented between March 2009 and August 2011 in our institution were identified. Species distribution and susceptibility were studied through the disk diffusion method. Results: Twenty-seven candidemia episodes were studied. Incidence varied from 0.3 to 0.7 by a thousand discharges (according to clinical service). Risk factors were hospitalization, preliminary use of antibiotics, aged people and underlying disease (renal failure, heart and lung disease). The most frequent species was C. albicans, followed by C. tropicalis, C. glabrata and C. krusei. Voriconazole was the antifungal showing the best in vitro performance. Amphotericin B, fluconazole and itraconazole presented variable results. Discussion: Incidence found was superior to that described in developed countries. Candida albicans constitute the most frequent species, with high sensitivity levels to fluconazole; Candida no albicans species must be monitored. Developing new research on the topic appears as fundamental to detect potential epidemiological variations.

Sarcoid-like cutaneous lesions in chronic adult paracoccidioidomycosis: report of two cases

ABSTRACT This study reports two cases of chronic paracoccidioidomycosis with sarcoid-like cutaneous lesions. The patients began the treatment in 2013 at Hospital Universitário Clementino Fraga Filho (HUCFF) of the Universidade Federal do Rio de Janeiro (UFRJ). The first case (mild form) was treated with trimethoprim-sulfamethoxazole (8 mg /kg per day, orally) for three months and, then, with half the dose for nine months; the second (moderate form), with itraconazole (200 mg per day, orally) for 12 months. We point out the rareness of the sarcoid-like cutaneous lesions and the differential diagnoses for other granulomatous diseases.

Paracoccidiodomicosis cutánea. Comunicación de un caso / Cutaneous paracoccidioidomycosis. Case report

La paracoccidioidomicosis es una micosis profunda, causada por el Paracoccidioides brasiliensis, hongo dimórfico que se localiza en el suelo de áreas endémicas. Se caracteriza por presentar lesiones cutáneomucosas y fundamentalmente de las vías respiratorias. El diagnóstico se realiza por examen directo, cultivo y la histopatología. El tratamiento de elección es el itraconazol. Se comunica el caso de un paciente de sexo masculino, de 43 años de edad, con diagnóstico de paracoccidiodomicosis cutánea crónica del adulto que tuvo buena respuesta al tratamiento con itraconazol (AU)

Paracoccidioidomycosis is a deep mycosis caused by Paracoccidioides brasiliensis, a dimorphic fungus located on the soil of endemic areas. It is characterized by skin lesions and mainly by the respiratory tract. Diagnosis is made by direct examination, culture and histopathology. Chosen treatment is itraconazole. A 43-year-old male patient with adult chronic cutaneous paracoccidiodomycosis diagnosis and good response to treatment with itraconazole is reported (AU)

Diagnostic-driven antifungal therapy in neutropenic patients using the D-index and serial serum galactomannan testing

Abstract Introduction Invasive mold disease is an important complication of patients with hematologic malignancies, and is associated with high mortality. A diagnostic-driven approach has been an alternative to the classical empiric antifungal therapy. In the present study we tested an algorithm that incorporated risk stratification using the D-index, serial serum galactomannan and computed tomographic-scan to guide the decision to start antifungal therapy in neutropenic patients. Patients and methods Between May 2010 and August 2012, patients with acute leukemia in induction remission were prospectively monitored from day 1 of chemotherapy until discharge or death with the D-index and galactomannan. Patients were stratified in low, intermediate and high risk according to the D-index and an extensive workup for invasive mold disease was performed in case of positive galactomannan (≥0.5), persistent fever, or the appearance of clinical manifestations suggestive of invasive mold disease. Results Among 29 patients, 6 (21%), 11 (38%), and 12 (41%) were classified as high, intermediate, and low risk, respectively. Workup for invasive mold disease was undertaken in 67%, 73% and 58% (p = 0.77) of patients in each risk category, respectively, and antifungal therapy was given to 67%, 54.5%, and 17% (p = 0.07). Proven or probable invasive mold disease was diagnosed in 67%, 45.5%, and in none (p = 0.007) of high, intermediate, and low risk patients, respectively. All patients survived. Conclusion A risk stratification using D-index was a useful instrument to be incorporated in invasive mold disease diagnostic approach, resulting in a more comprehensive antifungal treatment strategy, and to guide an earlier start of treatment in afebrile patients under very high risk.

Caracterización epidemiológica, clínica y de laboratorio de esporotricosis en pacientes de un hospital de tercer nivel en Lima-Perú, entre los años 1991 y 2014 / Epidemiological clinical and laboratory characterization of sporotrichosis in patients of a tertiary care hospital in Lima, Peru, from 1991 to 2014

Introducción: La esporotricosis es una afección endémica en numerosos países latinoamericanos y en el resto del mundo. En Perú se concentra en regiones con clima cálido y húmedo, siendo poco conocida en el resto del país. Objetivo: Describir las características epidemiológicas, clínicas y de laboratorio de esporotricosis en pacientes de un hospital de tercer nivel en Lima-Perú, entre los años 1991 y 2014.Método: Estudio descriptivo, retrospectivo, tipo serie de casos. Resultados: Se incluyeron 94 pacientes, la mayoría de los cuales fueron adultos del sexo masculino. Los lugares de adquisición más frecuentes fueron Cajamarca, Apurímac, y Amazonas. Las formas linfo-cutánea y cutánea fija fueron observadas con mayor frecuencia en adultos y, en especial de localización en los miembros superiores. Las localizaciones en la cabeza y el cuello fueron más frecuentes en niños. Co-morbilidades estuvieron presentes en 15% de pacientes, en particular en aquellos con la forma cutánea diseminada. El 78% de los cultivos procedentes de lesiones cutáneas fueron positivos dentro de siete días, y el tiempo de positividad fue mayor en cultivos de biopsia que en las muestras por raspado-aspirado. Conclusiones: Esporotricosis fue adquirida mayoritariamente en zonas del Perú con pobreza extrema. Las características clínicas, epidemiológicas y de laboratorio no difieren de las reportadas en otros estudios. El tiempo de positividad de los cultivos varía según tipo de muestra, lo que deberá ser mejor evaluado en estudios futuros.

Background: Sporothricosis is endemic in numerous Latin American countries and the rest of the world. In Peru is concentrated in regions with warm and humid climate being little known in the rest of the country. Aim: To describe the epidemiological, clinical and laboratory characteristics of patients diagnosed of sporotrichosis in a tertiary-care level hospital in Lima, Peru from 1991 to 2014. Methods: This was a retrospective, case series. Results: Ninety four patients were involved; most of them were male adults. This condition was acquired more frequently in Cajamarca, Apurímac, and Amazonas. Fixed and lymphocutaneous form were the most frequent forms of presentation in adults and were mostly distributed in upper limbs. Lesions located in head and neck were most frequent in children. Comorbidities were present in 15% of patients and were more frequent in those who presented disseminated cutaneous form. Seventy eight percent of cultures from skin lesions were positive within 7 days. The time to positivity of cultures was longer if the sample came from skin biopsies than skin scraping or skin aspiration. Conclusions: Most cases of sporotrichosis were acquired in areas of extreme poverty in Peru. The clinical, epidemiological and laboratory findings were similar to those reported elsewhere. The time to positivity of cultures varies based on the type of skin sample. This finding needs to be further evaluated in studies with an increased number of cases.

Candida parapsilosis: principal causa de candidemia en un hospital de referencia para adultos de Costa Rica / Candida parapsilosis: a major cause of bloodstream infection in a tertiary care hospital in Costa Rica

Background: Invasive Candida bloodstream infections are frequent and display high mortality in clinical practice. There is scarce published on this topic in Central America. Objective: To characterize the epidemiology of candidemia in a hospital setting in Costa Rica. Methods: 210 cases of nosocomial candidemia were analyzed in patients over 17 years of age, admitted to Hospital Mexico, between 2007 and 2011. Descriptive and temporary analyses were performed and the risk factors associated with C. parapsilosis and survival were evaluated. Results: The incidence rate of candidemia was 1.47 cases per 1,000 admissions. The non-albicans Candida represented 62% of the isolated yeasts. Except for 2009, C. parapsilosis was the most commonly isolated species in four out of the five years reviewed, followed by C. albicans. There was a strong association between C. parapsilosis, the presence of a central venous catheter (OR: 4.8, CI 95%: 1.8-14.6, p < 0.001) and the use of parenteral nutrition (p: 0.008). The 30-day mortality was 50%. Candida albicans displayed the highest mortality and C. parapsilosis the lowest. Patients who did not receive anti-fungal treatment showed a significantly higher probability of death. Conclusions: The high incidence of candidemia from C. parapsilosis is directly related to the use of central venous catheters and parenteral nutrition. There is a need for creating local guidelines addressing the use of central venous catheters and parenteral nutrition, as well as implementing hand hygiene protocols.

Introducción: Las infecciones invasoras por Candida son frecuentes y de alta mortalidad. Existe poca información publicada de la región centroamericana. Objetivo: Caracterizar la epidemiología de la candidemia en un hospital de Costa Rica. Métodos: Se analizaron 210 episodios de candidemia nosocomial en pacientes sobre 17 años de edad, entre los años 2007 y 2011. Se realizó un análisis descriptivo y temporal de la serie y evaluación de las características clínicas asociadas haciendo énfasis en C. parapsilosis. Resultados: La incidencia acumulada de candidemia fue 1,47 casos/1.000 admisiones. Las especies de Candida no albicans constituyeron 62% de las levaduras aisladas. Exceptuando el año 2009, C. parapsilosis fue la especie predominante en cuatro de los cinco años estudiados, seguida por C. albicans. Se demostró una fuerte asociación entre C. parapsilosis, la presencia de catéter venoso central (OR: 4,8, IC 95%: 1,8-14,6, p < 0,001) y el uso de nutrición parenteral (p: 0,008). La mortalidad a 30 días fue de 50%. Candida albicans mostró la mortalidad más alta y C. parapsilosis la más baja. Los pacientes que no recibieron tratamiento antifúngico presentaron un aumento significativo en la mortalidad. Conclusiones: La incidencia elevada de candidemia por C. parapsilosis está relacionada con los catéteres venosos centrales y la administración de nutrición parenteral. Para su control es necesario establecer guías locales para uso de los catéteres venosos centrales y la nutrición parenteral, así como implementar estrategias para promocionar la higiene de las manos.

Acute invasive pulmonary aspergillosis, shortly after occupational exposure to polluted muddy water, in a previously healthy subject / Aspergilose pulmonar invasiva aguda, logo após exposição ocupacional a água poluída barrenta, em indivíduo previamente saudável

Invasive pulmonary aspergillosis (IPA) predominantly occurs in severely neutropenic immunocompromised subjects. The occurrence of acute IPA after brief but massive exposure to Aspergillus conidia in previously healthy subjects has been documented, although only six such cases have been reported. The diagnosis was delayed in all six of the affected patients, five of whom died. We report the case of a 50-year-old HIV-negative male, a water pipeline maintenance worker, who presented with acute-onset dyspnea and fever one day after working for 2 h in a deep pit containing polluted, muddy water. Over a one-month period, his general condition deteriorated markedly, despite antibiotic therapy. Imaging showed bilateral diffuse nodules with cavitation, some of which were surrounded by ground-glass opacity suggestive of a halo sign (a hallmark of IPA). Cultures (of sputum/bronchial aspirate samples) and serology were positive for Aspergillus fumigatus. After being started on itraconazole, the patient improved. We conclude that massive exposure to Aspergillus conidia can lead to acute IPA in immunocompetent subjects.

A aspergilose pulmonar invasiva (API) ocorre predominantemente em indivíduos imunocomprometidos com neutropenia grave. A ocorrência de API aguda após exposição breve, mas maciça, a conídios de Aspergillus sp. em indivíduos previamente saudáveis já foi documentada, embora apenas seis casos tenham sido relatados. O diagnóstico foi tardio em todos os seis pacientes afetados, dos quais cinco foram a óbito. Relatamos o caso de um homem de 50 anos de idade, HIV negativo, trabalhador de manutenção de tubulação de água, que apresentou dispneia e febre de início agudo um dia após trabalhar 2 h em uma vala funda contendo água poluída e barrenta. Num período de um mês, seu estado geral se deteriorou acentuadamente, apesar da antibioticoterapia. Exames de imagem mostraram nódulos bilaterais difusos com cavitação, alguns dos quais circundados por opacidade em vidro fosco sugestiva de sinal do halo (uma característica da API). As culturas (de amostras de escarro/aspirado brônquico) e a sorologia foram positivas para Aspergillus fumigatus. Após iniciado o tratamento com itraconazol, o paciente melhorou. Concluímos que a exposição maciça a conídios de Aspergillus pode levar a API em indivíduos imunocompetentes.

Paracoccidioidomycosis treatment / Tratamento da paracoccidioidomicose

SUMMARYConsidered to be an emerging endemic mycosis in Latin America, paracoccidioidomycosis is characterized by a chronic course and involvement of multiple organs in immunocompromised hosts. Infection sequelae are mainly related to pulmonary and adrenal insufficiency. The host-parasite interaction results in different expressions of the immune response depending on parasite pathogenicity, fungal load and genetic characteristics of the host. A few controlled and case series reports have shown that azoles and fast-acting sulfa derivatives are useful treatment alternatives in milder forms of the disease. For moderate/severe cases, more prolonged treatments or even parenteral routes are required especially when there is involvement of the digestive tract mucosa, resulting in poor drug absorption. Although comparative studies have reported that shorter treatment regimens with itraconazole are able to induce cure in chronically-infected patients, there are still treatment challenges such as the need for more controlled studies involving acute cases, the search for new drugs and combinations, and the search for compounds capable of modulating the immune response in severe cases as well as the paradoxical reactions.

RESUMOConsiderada micose endêmica emergente na América Latina, a paracoccidioidomicose é caracterizada por uma evolução crônica e envolvimento de múltiplos órgãos em pacientes com comprometimento imunológico. Sequelas da infecção estão relacionadas principalmente à insuficiência pulmonar e adrenal. A interação hospedeiro-parasito resulta em diferentes expressões da resposta imune dependendo da patogenicidade do parasito, carga fúngica e características genéticas do hospedeiro. Alguns estudos controlados e séries de casos têm demonstrado que azóis de ação rápida e derivados de sulfa constituem alternativas terapêuticas úteis nas formas mais leves da doença. Para casos moderados/graves, tratamentos mais prolongados ou mesmo por via parenteral são necessários especialmente quando há envolvimento de mucosa do trato digestivo, resultando em absorção deficiente de drogas. Embora estudos comparativos tenham relatado que esquemas terapêuticos mais curtos com itraconazol sejam capazes de induzir cura em pacientes cronicamente infectados, ainda existem desafios no tratamento, tais como a necessidade de maior número de estudos controlados envolvendo casos agudos, busca por novas drogas e combinações, compostos capazes de modular a resposta imune nos casos graves, e reações paradoxais.

Primary cutaneous histoplasmosis developed in the penis of an immunocompetent patient

A 70-year-old male presenting a 3-month history of genital painless erythematous nodules in the balanopreputial sulcus was referred to our service. Histopathological exam presented a chronic dermatitis with epithelioid granulomas and Grocott staining revealed numerous fungal structures with a suggestive morphology of Histoplasma sp. Cultures evidenced Histoplasma capsulatum var. capsulatum. Treatment with oral itraconazole led to complete remission of lesions.

Clinical, epidemiological, and therapeutic profile of dermatophytosis

BACKGROUND: The cutaneous mycoses, mainly caused by dermatophyte fungi, are among the most common fungal infections worldwide. It is estimated that 10% to 15% of the population will be infected by a dermatophyte at some point in their lives, thus making this a group of diseases with great public health importance. OBJECTIVE: To analyze the clinical, epidemiological, and therapeutic profile of dermatophytosis in patients enrolled at the Dermatology service of Universidade do Estado do Pará, Brazil, from July 2010 to September 2012. METHOD: A total of 145 medical records of patients diagnosed with dermatophytosis were surveyed. Data were collected and subsequently recorded according to a protocol developed by the researchers. This protocol consisted of information regarding epidemiological and clinical aspects of the disease and the therapy employed. RESULTS: The main clinical form of dermatophyte infection was onychomycosis, followed by tinea corporis, tinea pedis, and tinea capitis. Furthermore, the female population and the age group of 51 to 60 years were the most affected. Regarding therapy, there was a preference for treatments that combine topical and systemic drugs, and the most widely used drugs were fluconazole (systemic) and ciclopirox olamine (topical). CONCLUSION: This study showed the importance of recurrent analysis of the epidemiological profile of dermatophytosis to enable correct therapeutic and preventive management of these conditions, which have significant clinical consequences, with chronic, difficult-totreat lesions that can decrease patient quality of life and cause disfigurement. .

Microsporum spp. onychomycosis: disease presentation, risk factors and treatment responses in an urban population

BACKGROUND: Dermatophytes are the main causative agent of all onychomycosis, but genus Microsporum is infrequent and the risk of acquiring the infection is often associated with exposure to risk factors. OBJECTIVES: To describe clinical characteristics of onychomycosis due to Microsporum onychomycosis in an urban population. METHODS: This was a retrospective analysis of the epidemiological and clinical features of 18Microsporum onychomycosis cases of a total of 4220 of onychomycosis cases diagnosed between May 2008 and September 2011 at the tertiary referral center for mycology in Guatemala. RESULTS: Eighteen cases of Microsporum onychomycosis (M. canis, n=10; M. gypseum, n=7; M. nanum, n=1) were identified (prevalence=0.43%). Infection was limited to nails only and disease duration ranged from 1 month to 20 years (mean=6.55 years). The toenails were affected in all cases except for a single M. gypseum case of fingernail. The most common clinical presentation was distal lateral subungual onychomycosis (12/18) followed by total dystrophic onychomycosis (5/18), and superficial white onychomycosis (1/18). M. gypseumpresented in 6 cases as distal lateral subungual onychomycosis and in 1 case like total dystrophic onychomycosis. Five cases (27.78%) were associated with hypertension, diabetes, and psoriasis. Treatment with terbinafine or itraconazole was effective. Two cases of M. canisdistal lateral subungual onychomycosis responded to photodynamic therapy. CONCLUSION: This is the largest reported series of Microsporum onychomycosis and demonstrates such a disease in an urban population. In 27.78% of the cases risk factors for infection were associated to comorbid states. We also report the first 2 cases of successfully treated M. canis onychomycosis with photodynamic therapy and a rare case of M. canis associated dermatophytoma. .

Paracoccidioidomycosis in a western Brazilian Amazon State: Clinical-epidemiologic profile and spatial distribution of the disease

Introduction: Paracoccidioidomycosis (PCM) is a systemic infection caused by the fungus Paracoccidioides brasiliensis. PCM is considered one of the most important systemic mycoses in Latin America. Methods: This is a clinical, epidemiological, retrospective, quantitative study of PCM cases in patients attending the National Health Service in the State of Rondônia in 1997-2012. The examined variables included sex, age group, year of diagnosis, education level, profession, place of residence, diagnostic test, prior treatment, medication used, comorbidities and case progress. Results: During the study period, 2,163 PCM cases were registered in Rondônia, and the mean annual incidence was 9.4/100,000 people. The municipalities with the highest rates were located in the southeastern region of Rondônia, and the towns of Pimenteiras do Oeste and Espigão do Oeste had the highest rates in the state, which were 39.1/100,000 and 37.4/100,000 people, respectively. Among all cases, 90.2% and 9.8% were observed in men and women, respectively, and most cases (58.2%) were observed in patients aged between 40 and 59 years. Itraconazole was used to treat 91.6% (1,771) of cases, followed by sulfamethoxazole in combination with trimethoprim (4.4% [85] of cases). One hundred thirty-one (6%) patients died. Conclusions: The State of Rondônia has a high incidence of PCM, and the municipalities in the southeastern region of the state were found to have the highest incidence rates of this disease. Our findings suggest that Rondônia is the state in the northern region with the highest mortality rate for PCM. .