ABSTRACT The antifungal activity of tacrolimus in combination with antifungal agents against different fungal species has been previously reported. Here we report the in vitro interactions between tacrolimus and amphotericin B, fluconazole, itraconazole, and caspofungin against 30 clinical isolates of both fluconazole-susceptible and fluconazole-resistant Trichosporon asahii. For these analyses, we used the broth microdilution method based on the M27-A3 technique and checkerboard microdilution method. Tacrolimus showed no activity against T. asahii strains (minimal inhibitory concentrations, MICs > 64.0 µg mL−1). However, a larger synergistic interaction was observed by the combinations tacrolimus + amphotericin B (96.67%) and tacrolimus + caspofungin (73.33%) against fluconazole-susceptible isolates. Combinations with azole antifungal agents resulted in low rates of synergism for this group (fluconazole + tacrolimus = 40% and itraconazole + tacrolimus = 10%). Antagonistic interactions were not observed. For the fluconazole-resistant T. asahii group, all tested combinations showed indifferent interactions. The synergism showed against fluconazole-susceptible T. asahii isolates suggests that the potential antifungal activity of tacrolimus deserves in vivo experimental investigation, notably, the combination of tacrolimus with amphotericin B or caspofungin.

RESUMO Objetivo: O sinal do halo consiste em uma área de opacidade em vidro fosco ao redor de lesões pulmonares em imagens de TC de tórax. Pacientes imunocompetentes e imunodeprimidos foram comparados quanto a características do sinal do halo a fim de identificar as de maior valor diagnóstico. Métodos: Estudo retrospectivo de tomografias realizadas em sete centros entre janeiro de 2011 e maio de 2015. Os pacientes foram classificados de acordo com seu estado imunológico. Dois radiologistas torácicos analisaram os exames a fim de determinar o número de lesões e sua distribuição, tamanho e contorno, bem como a espessura do halo e quaisquer outros achados associados. Resultados: Dos 85 pacientes avaliados, 53 eram imunocompetentes e 32 eram imunodeprimidos. Dos 53 pacientes imunocompetentes, 34 (64%) receberam diagnóstico de neoplasia primária. Dos 32 pacientes imunodeprimidos, 25 (78%) receberam diagnóstico de aspergilose. Lesões múltiplas e distribuídas aleatoriamente foram mais comuns nos imunodeprimidos do que nos imunocompetentes (p < 0,001 para ambas). A espessura do halo foi maior nos imunodeprimidos (p < 0,05). Conclusões: As etiologias do sinal do halo em pacientes imunocompetentes são bastante diferentes das observadas em pacientes imunodeprimidos. Embora halos mais espessos ocorram mais provavelmente em pacientes com doenças infecciosas, o número e a distribuição das lesões também devem ser levados em conta na avaliação de pacientes que apresentem o sinal do halo.

ABSTRACT Objective: The halo sign consists of an area of ground-glass opacity surrounding pulmonary lesions on chest CT scans. We compared immunocompetent and immunosuppressed patients in terms of halo sign features and sought to identify those of greatest diagnostic value. Methods: This was a retrospective study of CT scans performed at any of seven centers between January of 2011 and May of 2015. Patients were classified according to their immune status. Two thoracic radiologists reviewed the scans in order to determine the number of lesions, as well as their distribution, size, and contour, together with halo thickness and any other associated findings. Results: Of the 85 patients evaluated, 53 were immunocompetent and 32 were immunosuppressed. Of the 53 immunocompetent patients, 34 (64%) were diagnosed with primary neoplasm. Of the 32 immunosuppressed patients, 25 (78%) were diagnosed with aspergillosis. Multiple and randomly distributed lesions were more common in the immunosuppressed patients than in the immunocompetent patients (p < 0.001 for both). Halo thickness was found to be greater in the immunosuppressed patients (p < 0.05). Conclusions: Etiologies of the halo sign differ markedly between immunocompetent and immunosuppressed patients. Although thicker halos are more likely to occur in patients with infectious diseases, the number and distribution of lesions should also be taken into account when evaluating patients presenting with the halo sign.

Abstract: We report herein a case of thoracic infection due to Nocardia nova following lung re-transplantation performed for emphysema related to alpha-1-antitrypsin deficiency. The infection extended from the lung into the pleural space, thoracic wall, and mediastinum, presenting as pericarditis and empyema necessitatis. Nocardia nova was identified by 16S ribosomal deoxyribonucleic acid (rDNA) sequencing and phylogenetic analysis. According to a literature search of PubMed, LILACS and MEDLINE databases, we describe herein the first case of empyema necessitatis caused by N. nova species in a transplanted patient.

RESUMO A infecção por Candidaspp. está associada com alta mortalidade, principalmente quando o tratamento não é adequado, nem imediato. Assim, a correta identificação do gênero e espécie é necessária. O objetivo deste trabalho foi comparar 89 amostras de Candidaspp. pelos métodos manuais prova do tubo germinativo, auxanograma e CHROMagar em relação ao método automatizado ID 32C. As concordâncias entre os métodos em ordem crescente, medidas pelo coeficiente de Kappa, foram: ID 32C com CHROMagar Candida(κ = 0,38), ID 32C com auxanograma (κ = 0,59) e ID 32C com tubo germinativo (κ = 0,9). Uma das espécies identificadas neste trabalho foi a C. tropicalis, que demonstrou uma sensibilidade de 46,2%, especificidade de 95,2%, VPP de 80%, VPN de 81,1% e acurácia de 80,9% nos testes com CHROMagar Candidae uma sensibilidade de 76,9%, especificidade de 96,8%, VPP de 90,9%, VPN de 91% e acurácia de 91% nos testes de auxanograma. Portanto, o conhecimento das vantagens e limitações dos métodos é necessário para a escolha da melhor combinação entre os mesmos visando uma rápida e correta identificação das espécies de Candida.

SUMMARY Infection by Candidaspp. is associated with high mortality rates, especially when treatment is not appropriate and/or not immediate. Therefore, it is necessary to correctly identify the genus and species of Candida. The aim of this study was to compare the identification of 89 samples of Candida spp. by the manual methods germ tube test, auxanogram and chromogenic medium in relation to the ID 32C automated method. The concordances between the methods in ascending order, measured by the Kappa index were: ID 32C with CHROMagar Candida(κ = 0.38), ID 32C with auxanogram (κ = 0.59) and ID 32C with germ tube (κ = 0.9). One of the species identified in this study was C. tropicalis,which demonstrated a sensitivity of 46.2%, a specificity of 95.2%, PPV of 80%, NPV of 81.1%, and an accuracy of 80.9% in tests performed with CHROMagar Candida;and a sensitivity of 76.9%, a specificity of 96.8%, PPV of 90.9%, NPV of 91%, and an accuracy of 91% in the auxanogram tests. Therefore, it is necessary to know the advantages and limitations of methods to choose the best combination between them for a fast and correct identification of Candidaspecies.

Na edição de volume 38, número 2, versão online desta revista, Corsi e colaboradores apresentaram um texto muito elegante sobre os fatores que influenciam os alunos na escolha da especialidade médica. Este tema vem sendo abordado com grande frequência nas discussões do nosso Curso de Prática Educativa em Medicina, da Universidade Federal do Rio Grande do Sul, coordenado pelos professores Manfroi e Machado. A respeito deste assunto, temos algumas considerações sobre a nova geração de profissionais médicos e sua relação com o autodesenvolvimento profissional.

In volume 38, number 2, of the online version of this magazine, Corsi et al. presented a very elegant piece about the factors that influence students in their choice of medical specialty. This issue has been frequently addressed in discussions on our Course in Education Practice in Medicine at the Federal University of Rio Grande do Sul, coordinated by professors Manfroi and Machado. Regarding this matter we have some thoughts on the new generation of medical professionals and their relationship with professional self-development.

Bacilos não diftéricos são ubiquitários na natureza e comumente colonizam a pele e as membranas mucosas humanas, contudo eles raramente acarretam doença clínica. Apresentamos o primeiro relato de múltiplos nódulos causados por Corynebacterium striatum. A infecção ocorreu numa mulher imunocompetente de 72 anos de idade e o diagnóstico foi obtido pela coloração de Gram e cultivo de biópsia pulmonar. C. striatum deve ser reconhecido como potencial patógeno tanto em pacientes imunodeprimidos como em hospedeiros normais, em circunstâncias apropriadas.

Nondiphtherial corynebacteria are ubiquitous in nature and commonly colonize the skin and mucous membranes of humans, however they rarely account for clinical infection. We present the first reported case of multiple pulmonary nodules caused by Corynebacterium striatum. The infection occurred in a 72-year-old immunocompetent female, and the diagnosis was obtained by Gram's stain and culture of lung biopsy. C. striatumshould be recognized as a potential pathogen in both immunocompromised and normal hosts in the appropriate circumstances.

O estudo objetivou investigar a liberação in vitro de galactomanana (GM) em distintas espécies patogênicas de fungos do gênero Aspergillus. Grande variabilidade foi detectada tanto intra quanto inter espécies, sendo as cepas da espécie A. terreus relacionadas aos maiores índices de GM detectados. O significado in vivo destes achados permanece em aberto, porém merece investigação.

Here we investigate the extent to which different Aspergillus species release galactomannan (GM) in vitro. Marked variability was observed in GM reactivity between and within Aspergillus species, with A. terreus strains showing the highest GM indexes. The in vivo significance of these findings remains to be determined.

Apresentamos caso de histoplasmose com múltiplos nódulos pulmonares em paciente com história de melanoma. Este caso simula malignidade, incluindo o sinal de vaso nutridor que ocorre na metástase pulmonar. Enfatizamos a necessidade de considerar esta infecção em áreas onde a histoplasmose é endêmica.

We present a case of histoplasmosis with multiple pulmonary nodules in a patient with a history of melanoma. This case closely simulated malignancy, including the presence of feeding vessel sign, which occurs in pulmonary metastasis. We emphasize the need to be aware of this infection in areas where histoplasmosis is endemic.

Introduction Candida albicans is a commensal and opportunistic agent that causes infection in immunocompromised individuals. Several attributes contribute to the virulence and pathogenicity of this yeast, including the production of germ tubes (GTs) and extracellular hydrolytic enzymes, particularly phospholipase and proteinase. This study aimed to investigate GT production and phospholipase and proteinase activities in bloodstream isolates of C. albicans. Methods One hundred fifty-three C. albicans isolates were obtained from blood samples and analyzed for GT, phospholipase, and proteinase production. The assays were performed in duplicate in egg yolk medium containing bovine serum albumin and human serum. Results Detectable amounts of proteinase were produced by 97% of the isolates, and 78% of the isolates produced phospholipase. GTs were produced by 95% of the isolates. A majority of the isolates exhibited low levels of phospholipase production and high levels of proteinase production. Conclusions Bloodstream isolates of C. albicans produce virulence factors such as GT and hydrolytic enzymes that enable them to cause infection under favorable conditions.

Relatamos um caso de eumicetoma por grão branco causado por Scedosporium apiospermum em um hospedeiro imunocompetente que foi tratado com voriconazol oral e revisamos a literatura brasileira sobre scedosporiose.

We describe a case of white-grain eumycetoma caused by Scedosporium apiospermum in an immunocompetent host that was successfully treated with oral voriconazole, and we review the Brazilian reports on scedosporiosis.

OBJETIVO: Descrever as principais características clínico-radiológicas de pacientes com histoplasmose simulando câncer de pulmão. MÉTODOS: Estudo descritivo e retrospectivo baseado na análise dos prontuários médicos de 294 pacientes diagnosticados com histoplasmose no Laboratório de Micologia da Irmandade Santa Casa de Misericórdia de Porto Alegre, em Porto Alegre (RS), entre 1977 e 2011. O diagnóstico de histoplasmose foi estabelecido por cultura, exame histopatológico ou identificação de bandas M ou H por imunodifusão. Após identificar os pacientes com lesões macroscópicas e com achados compatíveis de malignidade em radiografia ou TC de tórax, os pacientes foram divididos em dois grupos: pacientes com história de câncer e lesões simulando metástases (grupo HC) e pacientes sem história de câncer com lesão simulando neoplasia primária (SHC). RESULTADOS: Dos 294 pacientes com histoplasmose, 15 apresentaram lesões simulando neoplasia primária ou metástases (9 e 6 nos grupos HC e SHC, respectivamente). A idade dos pacientes variou de 13 a 67 anos (mediana, 44 anos) Dos 15 pacientes, 14 (93%) apresentaram lesões pulmonares no momento da internação. CONCLUSÕES: A síndrome clínica e radiológica da doença neoplásica não se limita a malignidade, e, portanto, as doenças infecciosas granulomatosas devem ser consideradas no diagnóstico diferencial.

OBJECTIVE: To describe the main clinical and radiological characteristics of patients with histoplasmosis mimicking lung cancer. METHODS: This was a retrospective descriptive study based on the analysis of the medical records of the 294 patients diagnosed with histoplasmosis between 1977 and 2011 at the Mycology Laboratory of the Santa Casa Sisters of Mercy Hospital of Porto Alegre in the city of Porto Alegre, Brazil. The diagnosis of histoplasmosis was established by culture, histopathological examination, or immunodiffusion testing (identification of M or H precipitation bands). After identifying the patients with macroscopic lesions, as well as radiological and CT findings consistent with malignancy, we divided the patients into two groups: those with a history of cancer and presenting with lesions mimicking metastases (HC group); and those with no such history but also presenting with lesions mimicking metastases (NHC group). RESULTS: Of the 294 patients diagnosed with histoplasmosis, 15 had presented with lesions mimicking primary neoplasia or metastases (9 and 6 in the HC and NHC groups, respectively). The age of the patients ranged from 13 to 67 years (median, 44 years). Of the 15 patients, 14 (93%) presented with pulmonary lesions at the time of hospitalization. CONCLUSIONS: The clinical and radiological syndrome of neoplastic disease is not confined to malignancy, and granulomatous infectious diseases must therefore be considered in the differential diagnosis.

The goal of this study was to review 18 cases of phaeohyphomycosis in Rio Grande do Sul. The records of all of the patients with a diagnosis of phaeohyphomycosis between 1995-2010 were reviewed. Twelve of the 18 patients (66.6%) were male. The average age of the patients was 50 years old (range: 16-74 years). Eleven patients (61%) presented with subcutaneous lesions. Seven patients (38.8%) had received a solid organ transplant. In all of the cases, the presence of melanin in the fungal cells was determined by Fontana-Masson staining of tissue sections and documented. Among the 18 patients, a total of 11 different fungal species were isolated. The causative organisms included Exophiala jeanselmei, Alternaria, Curvularia, Cladophialophora and Colletotrichum gloeosporioides. To our knowledge, this review reports the first case of subcutaneous phaeohyphomycosis caused by C. gloeosporioides in a lung transplant patient. The number of reported cases of phaeohyphomycosis has increased in the last decade. In a number of cases, this increased incidence may be primarily attributed to iatrogenic immunodeficiency.

The extensive use of azole antifungal agents has promoted the resistance of Candida spp to these drugs. Candida glabrata is a problematic yeast because it presents a high degree of primary or secondary resistance to fluconazole. In Brazil, C. glabrata has been less studied than other species. In this paper, we compared the activity of three major classes of antifungal agents (azoles, echinocandins and polyenes) against fluconazole-susceptible (FS) and fluconazole-resistant (FR) C. glabrata strains. Cross-resistance between fluconazole and voriconazole was remarkable. Among the antifungal agents, the echinocandins were the most effective against FS and FR C. glabrata and micafungin showed the lowest minimal inhibitory concentrations.

OBJETIVO: Relatar os casos de 6 pacientes com bola fúngica (BF) na cavidade pleural por Aspergillus fumigatus. MÉTODOS: Entre 1980 e 2009, foram diagnosticados 391 pacientes com BF aspergilar no Complexo Hospitalar Santa Casa de Porto Alegre (RS). O diagnóstico de BF na cavidade pleural foi definido com exames de imagem demonstrando derrame e espessamento pleural com nível líquido; exame micológico direto demonstrando hifas septadas, consistentes com Aspergillus sp.; e cultura positiva para A. fumigatus no espécime cirúrgico da cavidade pleural. RESULTADOS: Dos 391 pacientes estudados, 6 (2%) preencheram os critérios diagnósticos estabelecidos. A média de idade desses 6 pacientes foi de 48 anos (variação, 29-66 anos), e 5 (83%) eram do sexo masculino. As queixas mais frequentes dos pacientes foram tosse, expectoração e hemoptise. Quatro (67%) dos pacientes tinham tuberculose curada. Todos os pacientes realizaram remoção cirúrgica da colonização fúngica, e houve infusão intrapleural com anfotericina B em 4; e 2 pacientes receberam tratamento antifúngico sistêmico v.o. Cinco pacientes melhoraram clinicamente, e um foi a óbito após a cirurgia. CONCLUSÕES: Em pacientes adultos com história de doença pulmonar cavitária ou fístula pleural, deve-se realizar uma investigação criteriosa levando em consideração a infecção fúngica, principalmente BF pulmonar. Portanto, a exploração laboratorial torna-se mais eficiente em relação aos recursos disponíveis para elucidação diagnóstica.

OBJECTIVE: To report the cases of 6 patients with fungus ball caused by Aspergillus fumigatus (aspergilloma) in the pleural cavity. METHODS: Between 1980 and 2009, 391 patients were diagnosed with aspergilloma at the Santa Casa Hospital Complex in Porto Alegre, Brazil. The diagnosis of aspergilloma in the pleural cavity was made through imaging tests revealing effusion and pleural thickening with air-fluid level; direct mycological examination revealing septate hyphae, consistent with Aspergillus sp.; and positive culture for A. fumigatus in the surgical specimen from the pleural cavity. RESULTS: Of the 391 patients studied, 6 (2%) met the established diagnostic criteria. The mean age of those 6 patients was 48 years (range, 29-66 years), and 5 (83%) were male. The most common complaints were cough, expectoration, and hemoptysis. Four patients (67%) had a history of tuberculosis that had been clinically cured. All of the patients were submitted to surgical removal of the aspergilloma, followed by intrapleural instillation of amphotericin B, in 4; and 2 received systemic antifungal treatment p.o. There was clinical improvement in 5 patients, and 1 died after the surgery. CONCLUSIONS: In adult patients with a history of cavitary lung disease or pleural fistula, a careful investigation should be carried out and fungal infection, especially aspergilloma, should be taken into consideration. In such cases, laboratory testing represents the most efficient use of the resources available to elucidate the diagnosis.