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1.
Emerg Infect Dis ; 27(4): 1077-1086, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33539721

RESUMO

Pneumonia caused by severe acute respiratory syndrome coronavirus 2 emerged in China at the end of 2019. Because of the severe immunomodulation and lymphocyte depletion caused by this virus and the subsequent administration of drugs directed at the immune system, we anticipated that patients might experience fungal superinfection. We collected data from 186 patients who had coronavirus disease-associated pulmonary aspergillosis (CAPA) worldwide during March-August 2020. Overall, 182 patients were admitted to the intensive care unit (ICU), including 180 with acute respiratory distress syndrome and 175 who received mechanical ventilation. CAPA was diagnosed a median of 10 days after coronavirus disease diagnosis. Aspergillus fumigatus was identified in 80.3% of patient cultures, 4 of which were azole-resistant. Most (52.7%) patients received voriconazole. In total, 52.2% of patients died; of the deaths, 33.0% were attributed to CAPA. We found that the cumulative incidence of CAPA in the ICU ranged from 1.0% to 39.1%.


Assuntos
Aspergillus fumigatus/isolamento & purificação , Unidades de Terapia Intensiva/estatística & dados numéricos , Aspergilose Pulmonar , Voriconazol/uso terapêutico , Idoso , Antifúngicos/uso terapêutico , /imunologia , /terapia , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/efeitos adversos , Incidência , Cooperação Internacional , Masculino , Avaliação de Processos e Resultados em Cuidados de Saúde , Aspergilose Pulmonar/diagnóstico , Aspergilose Pulmonar/tratamento farmacológico , Aspergilose Pulmonar/mortalidade , Sistema de Registros , Respiração Artificial/métodos , Fatores de Risco , /isolamento & purificação
2.
Rev Iberoam Micol ; 38(1): 16-18, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33500209

RESUMO

BACKGROUND: Patients with severe viral pneumonia are likely to receive high-dose immunomodulatory drugs to prevent clinical worsening. Aspergillus species have been described as frequent secondary pneumonia agents in severely ill influenza patients receiving steroids. COVID-19 patients admitted to Intensive Care Unit (ICU) are receiving steroids as part of their treatment and they share clinical characteristics with other patients with severe viral pneumonias. COVID-19 patients receiving steroids should be considered a putative risk group of invasive aspergillosis. CASE REPORT: We are reporting a SARS-CoV-2/Aspergillus section Fumigati coinfection in an elderly intubated patient with a history of pulmonary embolism treated with corticosteroids. The diagnosis was made following the ad hoc definitions described for patients admitted to ICU with severe influenza, including clinical criteria (fever for 3 days refractory to the appropriate antibiotic therapy, dyspnea, pleural friction rub, worsening of respiratory status despite antibiotic therapy and need of ventilator support), a radiological criterion (pulmonary infiltrate) and a mycological criterion (several positive galactomannan tests on serum with ratio ≥0.5). In addition, Aspergillus section Fumigati DNA was found in serum and blood samples. These tests were positive 4 weeks after the patient was admitted to the ICU. The patient received voriconazole and after two month in ICU his respiratory status improved; he was discharged after 6 weeks of antifungal treatment. CONCLUSIONS: Severely ill COVID-19 patients would be considered a new aspergillosis risk group. Galactomannan and Aspergillus DNA detection would be useful methods for Aspergillus infection diagnosis as they allow avoiding the biosafety issues related to these patients.


Assuntos
Aspergillus fumigatus/isolamento & purificação , /tratamento farmacológico , Coinfecção/diagnóstico , Imunocompetência , Imunossupressores/efeitos adversos , Aspergilose Pulmonar Invasiva/complicações , Metilprednisolona/efeitos adversos , /isolamento & purificação , Acetaminofen/uso terapêutico , Idoso , Anti-Infecciosos/uso terapêutico , Líquido da Lavagem Broncoalveolar/microbiologia , /terapia , Coinfecção/microbiologia , Coinfecção/terapia , Coinfecção/virologia , Terapia Combinada , Diagnóstico Diferencial , Quimioterapia Combinada , Enoxaparina/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Imunossupressores/uso terapêutico , Intubação Intratraqueal , Aspergilose Pulmonar Invasiva/diagnóstico , Aspergilose Pulmonar Invasiva/microbiologia , Aspergilose Pulmonar Invasiva/terapia , Masculino , Mananas/sangue , Metilprednisolona/uso terapêutico , Nasofaringe/virologia , Pneumonia por Mycoplasma/diagnóstico , Pseudomonas aeruginosa/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real , Respiração Artificial , Staphylococcus aureus/isolamento & purificação , Traqueia/microbiologia
3.
BMC Infect Dis ; 21(1): 121, 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33509115

RESUMO

BACKGROUND: Prolonged myelosuppression following CD19-directed CAR T-cell transfusion represents an important, yet underreported, adverse event. The resulting neutropenia and multifactorial immunosuppression can facilitate severe infectious complications. CASE PRESENTATION: We describe the clinical course of a 59-year-old patient with relapsed/refractory DLBCL who received Axicabtagene-Ciloleucel (Axi-cel). The patient developed ASTCT grade I CRS and grade IV ICANS, necessitating admission to the neurological ICU and prolonged application of high-dose corticosteroids and other immunosuppressive agents. Importantly, neutropenia was profound (ANC < 100/µl), G-CSF-refractory, and prolonged, lasting more than 50 days. The patient developed severe septic shock 3 weeks after CAR transfusion while receiving anti-fungal prophylaxis with micafungin. His clinical status stabilized with broad anti-infective treatment and intensive supportive measures. An autologous stem cell backup was employed on day 46 to support hematopoietic recovery. Although the counts of the patient eventually started to recover, he developed an invasive pulmonary aspergillosis, which ultimately lead to respiratory failure and death. Postmortem examination revealed signs of Candida glabrata pancolitis. CONCLUSIONS: This case highlights the increased risk for fatal infectious complications in patients who present with profound and prolonged cytopenia after CAR T-cell therapy. We describe a rare case of C. glabrata pancolitis associated with multifactorial immunosuppression. Although our patient succumbed to a fatal fungal infection, autologous stem cell boost was able to spur hematopoiesis and may represent an important therapeutic strategy for DLBCL patients with CAR T-cell associated bone marrow aplasia who have underwent prior stem cell harvest.


Assuntos
Anemia Aplástica/etiologia , Antígenos CD19/uso terapêutico , Aspergillus fumigatus/isolamento & purificação , Candida glabrata/isolamento & purificação , Imunoterapia Adotiva/efeitos adversos , Infecções Fúngicas Invasivas/etiologia , Anemia Aplástica/terapia , Antígenos CD19/efeitos adversos , Evolução Fatal , Humanos , Infecções Fúngicas Invasivas/microbiologia , Infecções Fúngicas Invasivas/terapia , Linfoma Difuso de Grandes Células B/terapia , Masculino , Pessoa de Meia-Idade
5.
Mycoses ; 63(12): 1368-1372, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32965042

RESUMO

BACKGROUND: Critically ill patients with coronavirus disease-2019 (COVID-19) are at the theoretical risk of invasive pulmonary aspergillosis (IPA) due to known risk factors. PATIENTS/METHODS: We aimed to describe the clinical features of COVID-19-associated pulmonary aspergillosis at a single centre in New York City. We performed a retrospective chart review of all patients with COVID-19 with Aspergillus isolated from respiratory cultures. RESULTS: A total of seven patients with COVID-19 who had one or more positive respiratory cultures for Aspergillus fumigatus were identified, all of whom were mechanically ventilated in the ICU. Four patients were classified as putative IPA. The median age was 79 years, and all patients were male. The patients had been mechanically ventilated for a mean of 6.8 days (range: 1-14 days) before Aspergillus isolation. Serum galactomannan level was positive for only one patient. The majority of our cases received much higher doses of glucocorticoids than the dosage with a proven mortality benefit. All four patients died. CONCLUSIONS: Vigilance for secondary fungal infections will be needed to reduce adverse outcomes in critically ill patients with COVID-19.


Assuntos
Aspergillus fumigatus/isolamento & purificação , Infecções por Coronavirus/complicações , Aspergilose Pulmonar Invasiva/complicações , Pneumonia Viral/complicações , Idoso , Idoso de 80 Anos ou mais , Infecções por Coronavirus/terapia , Evolução Fatal , Humanos , Unidades de Terapia Intensiva , Aspergilose Pulmonar Invasiva/microbiologia , Aspergilose Pulmonar Invasiva/terapia , Masculino , Cidade de Nova Iorque/epidemiologia , Pandemias , Pneumonia Viral/terapia , Respiração Artificial , Estudos Retrospectivos , Fatores de Risco
6.
BMC Infect Dis ; 20(1): 608, 2020 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-32807082

RESUMO

BACKGROUND: Invasive fungal pneumonia is a severe infectious disease with high mortality in immunocompromised patients. However, the clinical diagnosis of the pathogen(s) remains difficult since microbiological evidence is difficult to acquire. CASE PRESENTATION: Here, we report a case of pulmonary fungal infection detected by next-generation sequencing (NGS) of bronchoalveolar lavage fluid (BALF) in a 61-year-old male with corticosteroid-treated dermatomyositis. Cytomegalovirus and influenza A virus infections were confirmed by nucleic acid detection and treated with antiviral medicine. The patient had been diagnosed with severe pneumonia and treated with empiric broad-spectrum antibacterial and antifungal drugs before bronchoscopy was performed. The patient responded poorly to those empiric treatments. Three fungi were found by NGS in the BALF, namely, Pneumocystis jirovecii, Aspergillus fumigatus and Rhizopus oryzae. After adjusting the patient's treatment plan according to the NGS results, he improved significantly. CONCLUSIONS: This case highlights the combined application of NGS and traditional tests in the clinical diagnosis of pulmonary invasive fungal disease. NGS is proposed as an important adjunctive diagnostic approach for identifying uncommon pathogens.


Assuntos
Líquido da Lavagem Broncoalveolar/microbiologia , Dermatomiosite/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala , Pneumopatias Fúngicas/diagnóstico , Antifúngicos/uso terapêutico , Aspergillus fumigatus/genética , Aspergillus fumigatus/isolamento & purificação , DNA Fúngico/química , DNA Fúngico/metabolismo , Dermatomiosite/complicações , Humanos , Pulmão/diagnóstico por imagem , Pneumopatias Fúngicas/tratamento farmacológico , Pneumopatias Fúngicas/microbiologia , Masculino , Pessoa de Meia-Idade , Pneumocystis carinii/genética , Pneumocystis carinii/isolamento & purificação , Rhizopus/genética , Rhizopus/isolamento & purificação , Tomografia Computadorizada por Raios X
7.
Zhonghua Er Ke Za Zhi ; 58(8): 646-652, 2020 Aug 02.
Artigo em Chinês | MEDLINE | ID: mdl-32842385

RESUMO

Objective: To analyze the clinical features of cystic fibrosis (CF) associated allergic bronchopulmonary aspergillosis (ABPA) in children. Methods: A retrospective study was performed in 22 children who were diagnosed with CF associated ABPA in Beijing Children's Hospital affiliated to Capital Medical University from March 2010 to March 2020. The clinical features, imaging characteristics, laboratory results and the prognosis were reviewed. Results: A total of 22 cases met the diagnostic criterion, including 12 males and 10 females. The age of diagnosis was (10.4±2.8) years and the age of onset was (5.5±4.4) years. Clinical manifestations included cough and expectoration (22 cases), recurrent wheezing (15 cases), hemoptysis (7 cases), failure to thrive (12 cases), pancreatitis (10 cases), hepatomegaly (7 cases), splenomegaly (4 cases) and steatorrhea (4 cases). CT scans of all the patients showed pulmonary infiltrates and central bronchiectasis, combined with mucoid impaction in 17 cases and high density mucus plug in 12 cases. Eosinophilia was found in 18 patients. Total IgE and serum levels of A. fumigatus-specific IgE were elevated in all 22 patients. Positive culture of sputum or bronchoalvedar lauage fluid for fungus were in 15 cases, with single Aspergillus infection in 8 cases and mixed Aspergillus infection in 3 cases. The predominant bacteria found in the airways were Pseudomonas aeruginosa (17 cases), followed by staphylococcas. aureus (6 cases) and stenotrophomonas. maltophilia (5 cases). Pulmonary function revealed obstructive ventilation dysfunction in 4 cases, mixed dysfunction in 11 cases, and small airway dysfunction in 4 cases. Regarding the treatment, 3 were treated only with systemic corticosteroid, while the remaining 19 cases also received antifungal agents.The follow up continued for 1-7 years, and 6 maintained remission, 10 had recurrent episodes, 1 died, and 5 lost to follow up. Conclusions: CF associated ABPA is extremely rare in China. The overlapping clinical, radiographic, and immunologic features of these two diseases make the diagnosis challenging. Systemic corticosteroids are considered the first-line therapy for these patients, and adjuvant antifungal agents may be helpful. Recurrence rate in our center is high.


Assuntos
Aspergilose Broncopulmonar Alérgica/complicações , Aspergillus fumigatus/isolamento & purificação , Fibrose Cística/complicações , Escarro/microbiologia , Aspergilose Broncopulmonar Alérgica/tratamento farmacológico , Criança , China , Fibrose Cística/diagnóstico , Fibrose Cística/microbiologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento
8.
Arq. bras. med. vet. zootec. (Online) ; 72(4): 1363-1368, July-Aug. 2020. ilus
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1131490

RESUMO

In this study we describe the epidemiology, clinical signs, and pathology of an outbreak of avian aspergillosis in alternative breeding in the southern region of Rio Grande do Sul, Brazil. Between the fifth and tenth day of life, 360 chicks from a flock of 4000 developed unspecific clinical signs and died. The birds were housed in a reused aviary litter, without previous treatment. In 11 six-day-old female ISA Brown chicks (Gallus gallus domesticus), necropsy revealed firm, yellowish-white, multinodular lesions extending from the pleura to the lung parenchyma. Histologically, a granulomatous, multifocal to coalescent pneumonia was observed. Granulomas were characterized by central necrosis, with heterophil and epithelioid macrophage infiltration and presence of countless Y-shaped intralesional septate hyphae morphologically compatible with Aspergillus spp. The diagnosis through isolation confirmed Aspergillus fumigatus. We highlight the importance of aspergillosis as a primary cause of diseases in the respiratory tract of young birds in alternative breeding. Measures to prevent aspergillosis mainly regarding the reuse of aviary litter are essential in poultry husbandry to prevent economic losses, reduce environmental contamination and mitigate the potential risk to public health.(AU)


Descrevem-se os aspectos epidemiológicos e patológicos de um surto de aspergilose aviária em criação alternativa na região sul do Rio Grande do Sul, Brasil. De um lote de 4000 pintainhas, entre o quinto e o 10º dia de vida, 360 aves apresentaram sinais clínicos inespecíficos e morreram. As aves foram alojadas em cama reutilizada do aviário, sem tratamento prévio. Na necropsia de 11 pintainhas (Gallus gallus domesticus), fêmeas, seis dias de idade da linhagem Isa Brown, foram observadas no pulmão lesões multinodulares, branco-amareladas e firmes, que se estendiam da pleura ao parênquima. Histologicamente foi observada pneumonia granulomatosa, multifocal a coalescente. Os granulomas eram caracterizados por necrose central, com infiltrado inflamatório de heterófilos, macrófagos, células epitelioides com presença de inúmeras hifas septadas intralesionais, semelhantes à letra "Y", morfologicamente compatíveis com Aspergillus spp. O diagnóstico foi confirmado pelo isolamento de Aspergillus fumigatus. Alerta-se para a importância da aspergilose como causa primária de afecções no trato respiratório de aves jovens em criações alternativas. Medidas preventivas relacionadas ao manejo dessas aves são indispensáveis principalmente quanto à reutilização da cama dos aviários, a fim de evitar perdas econômicas, reduzir a contaminação ambiental e o potencial risco à saúde pública.(AU)


Assuntos
Animais , Aves Domésticas/microbiologia , Aspergilose/epidemiologia , Aspergillus fumigatus/isolamento & purificação , Galinhas/microbiologia , Brasil
9.
BMC Infect Dis ; 20(1): 535, 2020 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-32703183

RESUMO

BACKGROUND: Breakthrough invasive fungal infections (bIFIs) are an area of concern in the scarcity of new antifungals. The mixed form of bIFIs is a rare phenomenon but could be potentially a troublesome challenge when caused by azole-resistant strains or non-Aspergillus fumigatus. To raise awareness and emphasize diagnostic challenges, we present a case of mixed bIFIs in a child with acute lymphoblastic leukemia. CASE PRESENTATION: A newly diagnosed 18-month-old boy with acute lymphoblastic leukemia was complicated with prolonged severe neutropenia after induction chemotherapy. He experienced repeated episodes of fever due to extended-spectrum beta-lactamase-producing Escherichia coli bloodstream infection and pulmonary invasive fungal infection with Aspergillus fumigatus (early-type bIFIs) while receiving antifungal prophylaxis. Shortly after pulmonary involvement, his condition aggravated by abnormal focal movement, loss of consciousness and seizure. Cerebral aspergillosis with Aspergillus niger diagnosed after brain tissue biopsy. The patient finally died despite 108-day antifungal therapy. CONCLUSIONS: Mixed bIFIs is a rare condition with high morbidity and mortality in the patients receiving immunosuppressants for hematological malignancies. This case highlights the clinical importance of Aspergillus identification at the species level in invasive fungal infections with multiple site involvement in the patients on antifungal prophylaxis.


Assuntos
Antifúngicos/uso terapêutico , Aspergillus fumigatus/imunologia , Aspergillus niger/genética , Coinfecção/diagnóstico , Aspergilose Pulmonar Invasiva/diagnóstico , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Neuroaspergilose/diagnóstico , Antígenos de Fungos/análise , Aspergillus fumigatus/isolamento & purificação , Aspergillus niger/isolamento & purificação , Cerebelo/microbiologia , Cerebelo/patologia , Criança , Coinfecção/microbiologia , Evolução Fatal , Humanos , Quimioterapia de Indução/efeitos adversos , Lactente , Aspergilose Pulmonar Invasiva/sangue , Aspergilose Pulmonar Invasiva/microbiologia , Masculino , Neuroaspergilose/microbiologia , Neutropenia/induzido quimicamente , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico
10.
J Zoo Wildl Med ; 51(2): 448-454, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32549578

RESUMO

A freshly dead juvenile bottlenose dolphin (Tursiops truncatus), recovered from the waters near Sand Key, Clearwater, FL, was imaged postmortem using computed tomography and magnetic resonance imaging prior to conventional necropsy. The pattern of imaging findings in the brain was compatible with severe multifocal meningoencephalitis with intralesional necrosis and/or hemorrhage, and the pattern of imaging findings in the lungs was compatible with severe multifocal bronchopneumonia. The subsequent investigation included necropsy, histology, culture, and molecular diagnostics and demonstrated disseminated coinfection of dolphin morbillivirus and Aspergillus fumigatus. This is the first report documenting the cross-sectional imaging findings of this important cetacean comorbidity and demonstrates advances in modern, cooperative investigations of marine mammal mortality events.


Assuntos
Aspergilose/veterinária , Aspergillus fumigatus/isolamento & purificação , Golfinho Nariz-de-Garrafa , Coinfecção/veterinária , Infecções por Morbillivirus/veterinária , Morbillivirus/isolamento & purificação , Animais , Animais Selvagens , Aspergilose/diagnóstico , Aspergilose/microbiologia , Coinfecção/diagnóstico , Coinfecção/microbiologia , Coinfecção/virologia , Imagem por Ressonância Magnética/veterinária , Infecções por Morbillivirus/diagnóstico , Infecções por Morbillivirus/virologia , Tomografia Computadorizada por Raios X/veterinária
11.
J Mycol Med ; 30(3): 101002, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32507472

RESUMO

INTRODUCTION: Rhino-orbital-aspergillosis (ROA) is a rare but serious disease in immunocompetent patients. Diagnosis is often delayed due to the absence of specific clinical symptoms. We describe the case of a patient who presented initially with ROA which spread progressively to the right ethmoid-sphenoid sinuses and then to the brain. OBSERVATION: A 61-year-old patient with a history of well-controlled diabetes presented with a sudden severe decrease in right visual acuity. Cerebral MRI showed the presence of an infiltrate in the right orbital apex extending to the homolateral cavernous sinus without any cerebral involvement. A diagnosis of right orbital myositis was made and corticosteroid therapy was started. His symptoms worsened progressively leading to quasi-blindness. A new MRI showed the development of right sphenoid-ethmoid osteolytic lesions. A fungal aetiology was suspected and tests for fungal biomarkers found a ß-(1-3)-D-glucan level of 99pg/ml but negative galactomannan. An ethmoid biopsy was performed for histological and mycological investigations, including the detection of Aspergillus DNA by qPCR. qPCR was positive and culture resulted in the isolation of multi-sensitive Aspergillus fumigatus. Treatment was initiated with voriconazole. Due to persistence of blindness and the appearance of a lesion extending to the right frontal lobe, surgical excision was performed followed by antifungal treatment for a total duration of 1year. The patient is currently stable, but has persistence of blindness in the right eye. CONCLUSION: Invasive ROA is a rare but serious disease in immunocompetent patients which should be evoked in the differential diagnosis of a tumour or vasculitis. Early diagnosis is essential for optimal management.


Assuntos
Aspergilose/diagnóstico , Infecções Fúngicas do Sistema Nervoso Central/diagnóstico , Infecções Oculares Fúngicas/microbiologia , Imunocompetência , Infecções Fúngicas Invasivas/diagnóstico , Rinite/microbiologia , Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Aspergilose/microbiologia , Aspergillus fumigatus/isolamento & purificação , Cegueira/diagnóstico , Cegueira/microbiologia , Infecções Fúngicas do Sistema Nervoso Central/complicações , Infecções Fúngicas do Sistema Nervoso Central/tratamento farmacológico , Infecções Fúngicas do Sistema Nervoso Central/microbiologia , Complicações do Diabetes/tratamento farmacológico , Complicações do Diabetes/microbiologia , Infecções Oculares Fúngicas/complicações , Infecções Oculares Fúngicas/diagnóstico , Infecções Oculares Fúngicas/tratamento farmacológico , Humanos , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/microbiologia , Masculino , Pessoa de Meia-Idade , Neuroaspergilose/complicações , Neuroaspergilose/diagnóstico , Neuroaspergilose/tratamento farmacológico , Neuroaspergilose/microbiologia , Doenças Orbitárias/diagnóstico , Doenças Orbitárias/tratamento farmacológico , Doenças Orbitárias/microbiologia , Rinite/complicações , Rinite/diagnóstico , Rinite/tratamento farmacológico , Voriconazol/uso terapêutico
12.
J Mycol Med ; 30(3): 100985, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32418638

RESUMO

Aspergillus fumigatus can cause a wide range of diseases, from hypersensitivity to invasive infection. Invasive disease usually occurs in severely immunocompromised patients with deep and prolonged neutropenia. It is a less well-recognized complication in critically ill patients without traditional risk factors. We describe a case of early invasive pulmonary aspergillosis (IPA) secondary to Legionella pneumophila serogroup 1 pneumonia in a patient on an intensive care unit (ICU). In addition to commonly accepted risk factors for IPA in ICU patients, we hypothesis that L. pneumophilia pneumonia could enhance this type of infection. We also reviewed all published cases of coinfection with L. pneumophila and A. fumigatus to assess whether Legionnaires' disease could be a risk factor for IPA.


Assuntos
Estado Terminal , Aspergilose Pulmonar Invasiva/complicações , Aspergilose Pulmonar Invasiva/diagnóstico , Doença dos Legionários/complicações , Doença dos Legionários/diagnóstico , Idoso , Aspergillus fumigatus/isolamento & purificação , Diagnóstico Diferencial , França , Humanos , Unidades de Terapia Intensiva , Aspergilose Pulmonar Invasiva/microbiologia , Legionella pneumophila/isolamento & purificação , Doença dos Legionários/microbiologia , Masculino
13.
Zhonghua Jie He He Hu Xi Za Zhi ; 43(5): 437-443, 2020 May 12.
Artigo em Chinês | MEDLINE | ID: mdl-32450632

RESUMO

Objective: To explore the clinical characteristics, risk factors and possible inflammatory response mechanisms in critically ill patients with influenza and invasive pulmonary aspergillosis co-infection. Methods: Sixty-four patients with severe influenza virus pneumonia were included in the RICU of the China-Japanese Friendship Hospital from November 1(st), 2017 to March 31(th), 2018. There were 33 males and 31 females, with an average age of (55±14) years. T-tests or χ(2) test were applied for comparisons between the two groups. Fifteen patients were complicated with IPA and were classified as the IPA group, while the other 49 served as the control group. The clinical characteristics, laboratory examinations, and endoscopic manifestations were compared between the two groups and the risk factors for severe influenza virus pneumonia with IPA were analyzed by multivariate logistic regression. The possible mechanisms of inflammatory response were explored by comparing the differences of plasma inflammatory factors between the two groups. Results: Seven patients (7/15, 47.7%) in the IPA group died. The percentage of wheezing in the IPA group (n=13) was significantly higher than that in the control group (n=25) (P<0.05). The values of WBC [(11.0±2.7)×10(9)/L], and the levels of blood GM [(2.46±0.80) µg/L] and BALF GM [(5.30±0.98) µg/L] in the IPA group were significantly higher than those in the control group, while PCT was lower than that in the control group[(6.1±3.3)×10(9)/L, (0.33±0.07) µg/L and (0.73±0.17) µg/L, respectively] (P<0.01). Compared with the control group, the chest CT of the IPA group showed more nodules along the bronchial bundle (n=11), massive consolidation shadow (n=9), halo sign (n=3) and cavity/air crescent sign (n=5) (control group: 8, 11, 0 and 4, respectively) (P<0.05). Airway mucosal pseudomembrane formation (n=12) and airway stenosis (n=10) were significantly higher in the IPA group than in the control group (2 and 17) (P<0.05). Multivariate logistic regression analysis suggested that the history of glucocorticoid use after ICU admission, normal PCT, multiple nodules, halo signs and pseudomembrane formation under endoscopy were risk factors for severe influenza virus pneumonia with IPA. The plasma pro-inflammatory factors IFN-γ [IPA group: 34.9 (20.6-64.0) µg/L] and IL-2 [16.2 (8.9-20.7) µg/L] were significantly lower than in patients without IPA [control group: 65.2 (43.8-124.5) µg/L and 20.4 (14.6-28.8) µg/L, respectively] (P<0.05); while the inflammatory inhibitors IL-4 [51.6 (32.7-69.7) µg/L) and IL-10 [15.7 (11.8-92.5) µg/L] were higher in IPA group [control group 8.9 (6.1-15.0) µg/L and 7.8 (3.6-21.8) µg/L] (P<0.05). SOFA scores showed a negative correlation with IFN-γ (r=-0.658, P=0.02) and IL-6 (r=-0.602, P=0.038), but a positive correlation with IL-10 (r=0.641, P=0.025) by Spearman correlation analysis. Conclusions: Some relatively specific clinical characteristics could be found in severe influenza pneumonia complicated with IPA. IPA should be highly suspected when a patient had a history of glucocorticoid use after ICU admission, high WBCs in the course of treatment without significant increase of PCT,multiple nodules along the airway distribution and the characteristic pseudomembrane formation under bronchoscopy. Influenza virus caused imbalance of immune responses, leading to a weakened pro-inflammatory response and a strengthened inflammatory suppression, which might be a possible mechanism for IPA development.


Assuntos
Coinfecção/epidemiologia , Influenza Humana/complicações , Aspergilose Pulmonar Invasiva/epidemiologia , Pneumonia Viral/epidemiologia , Adulto , Idoso , Aspergillus fumigatus/isolamento & purificação , China/epidemiologia , Feminino , Humanos , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
14.
J Infect Chemother ; 26(8): 847-850, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32414688

RESUMO

Aspergillus empyema is treated with either systemic administration of antifungal drugs or surgery, but the mortality rate is very high. Here, we report a case of Aspergillus empyema successfully treated using combined intrathoracic and intravenous administration of voriconazole (VRCZ). Treatment success was achieved by monitoring VRCZ plasma trough concentration. The patient was a 71-year-old Japanese woman diagnosed with Aspergillus empyema whom we started on intravenous administration of VRCZ. Although penetration of VRCZ into the pleural effusion was confirmed, the level was below 1 µg/mL, which is the minimum inhibitory concentration for Aspergillus fumigatus determined by antifungal susceptibility testing in pleural effusion culture. Therefore, we initiated combination therapy with intrathoracic and intravenous administration of VRCZ. VRCZ 200 mg was first dissolved in 50-100 mL of saline and administered into the thoracic cavity via a chest tube. The chest tube was clamped for 5-6 h, and then VRCZ solution was excreted though the chest tube. When a single dose of the VRCZ was administered into the intrathoracic space, the plasma concentration before intravenous administration increased from 1.45 µg/mL on day 27 to 1.53 µg/mL on day 28. Although intravenous administration was continued, the VRCZ plasma trough concentration decreased to 1.36 µg/mL on day 29. We therefore decided on an intrathoracic administration schedule of 2-3 times a week. Intrathoracic administration was performed 14 times in total until fenestration surgery on day 64. Our case suggests that combined intrathoracic and intravenous administration of VRCZ may be a valid treatment option for Aspergillus empyema.


Assuntos
Antifúngicos/administração & dosagem , Aspergilose/tratamento farmacológico , Aspergillus fumigatus/isolamento & purificação , Empiema/tratamento farmacológico , Voriconazol/administração & dosagem , Administração Intravenosa , Idoso , Tubos Torácicos , Monitoramento de Medicamentos , Quimioterapia Combinada , Empiema/microbiologia , Feminino , Humanos , Derrame Pleural/microbiologia , Resultado do Tratamento
15.
Invest Ophthalmol Vis Sci ; 61(4): 48, 2020 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-32347916

RESUMO

Purpose: We characterized the effects of Honokiol (HNK) on Aspergillus fumigatus-caused keratomycosis and the underlying mechanisms. HNK is known to have anti-inflammatory and antifungal properties, but the influence on fungal keratitis (FK) remains unknown. Methods: In ex vivo, minimum inhibitory concentration and Cell Count Kit-8 assay were carried out spectrophotometrically to provide preferred concentration applied in vivo. Time kill assay pointed that HNK was fungicidal and fungistatic chronologically. Adherence assay, crystal violet staining, and membrane permeability assay tested HNK effects on different fungal stages. In vivo, clinical scores reflected the improvement degree of keratitis outcome. Myeloperoxidase (MPO) assay, flow cytometry (FCM), and immunohistofluorescence staining (IFS) were done to evaluate neutrophil infiltration. Plate count detected HNK fungicidal potentiality. RT-PCR, Western blot, and enzyme-linked immunosorbent assay (ELISA) verified the anti-inflammatory activity of HNK collaboratively. Results: In vitro, MIC90 HNK was 8 µg/mL (no cytotoxicity), and Minimal Fungicidal Concentration (MFC) was 12 µg/mL for A. fumigatus. HNK played the fungistatic and fungicidal roles at 6 and 24 hours, respectively, inhibiting adherence at the beginning, diminishing biofilms formation, and increasing membrane permeability all the time. In vivo, HNK improved C57BL/6 mice outcome by reducing disease severity (clinical scores), neutrophil infiltration (MPO, FCM, and IFS), and fungal loading (plate count). RT-PCR, Western blot, and ELISA revealed that HNK downregulated mRNA and protein expression levels of Toll-like receptor-2 (TLR-2), high mobility group box 1 (HMGB1), IL-1ß, and TNF-α. Conclusions: Our study suggested HNK played antifungal and anti-inflammatory roles on keratomycosis by reducing survival of fungi, infiltration of leucocytes, and expression of HMGB1, TLR-2, and proinflammatory cytokines, providing a potential treatment for FK.


Assuntos
Anti-Infecciosos/farmacologia , Aspergilose/tratamento farmacológico , Aspergillus fumigatus/isolamento & purificação , Compostos de Bifenilo/farmacologia , Infecções Oculares Fúngicas/tratamento farmacológico , Lignanas/farmacologia , Animais , Aspergilose/diagnóstico , Western Blotting , Citocinas/efeitos dos fármacos , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Infecções Oculares Fúngicas/microbiologia , Feminino , Ceratite/tratamento farmacológico , Ceratite/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória , Reação em Cadeia da Polimerase em Tempo Real/métodos , Receptor 2 Toll-Like/efeitos dos fármacos , Resultado do Tratamento
16.
Transl Res ; 219: 1-12, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32165060

RESUMO

Invasive aspergillosis (IA) is a major cause of critical illness in immunocompromised (IC) patients. However, current fungal tests are limited. Disease-specific gene expression patterns in circulating host cells show promise as novel diagnostics, however it is unknown whether such a 'signature' exists for IA and the effect of iatrogenic immunosuppression on any such biomarkers. Male BALB/c mice were separated into 6 experimental groups based on Aspergillus fumigatus inhalational exposure and IC status (no immunosuppression, cyclophosphamide, and corticosteroids). Mice were sacrificed 4 days postinfection. Whole blood was assayed for transcriptomic responses in peripheral white blood cells via microarray. An elastic net regularized logistic regression was employed to develop classifiers of IA based on gene expression. Aspergillus infection triggers a powerful response in non-IC hosts with 2718 genes differentially expressed between IA and controls. We generated a 146-gene classifier able to discriminate between non-IC infected and uninfected mice with an AUC of 1. However, immunosuppressive medications exhibited a confounding effect on this transcriptomic classifier. After controlling for the genomic effects of immunosuppression, we were able to generate a 187-gene classifier with an AUC of 0.92 in the absence of immunosuppression, 1 with cyclophosphamide, and 0.9 with steroids. The host transcriptomic response to IA is robust and conserved. Pharmacologic perturbation of the host immune response has powerful effects on classifier performance and must be considered when developing such novel diagnostics. When appropriately designed, host-derived peripheral blood transcriptomic responses demonstrate the ability to accurately diagnose Aspergillus infection, even in the presence of immunosuppression.


Assuntos
Aspergilose/diagnóstico , Aspergillus fumigatus/genética , Genes Fúngicos , Hospedeiro Imunocomprometido , Transcrição Genética , Animais , Aspergilose/genética , Aspergilose/microbiologia , Aspergillus fumigatus/isolamento & purificação , Aspergillus fumigatus/patogenicidade , Estudos de Casos e Controles , Contagem de Colônia Microbiana , Pulmão/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Reprodutibilidade dos Testes
19.
BMJ Case Rep ; 13(2)2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32060111

RESUMO

Primary cutaneous aspergillosis (PCA) occurs through inoculation of fungal spores directly into the skin from the environment through disrupted skin such as in burns, surgery or penetrating trauma patients. Most cases reported in literature were in the immunocompromised, rarely in immunocompetent patients. The characteristic lesion of cutaneous aspergillosis is a black eschar on a red plaque, or nodule at the site of skin injury. The diagnosis of PCA can be made by identifying hyphal forms on routine H&E staining or special stains such as periodic acid-Schiff or Gomori methenamine-silver stains on skin biopsy and by fungal cultures. We report a case of an 80-year-old farmer who developed cutaneous aspergillosis after a surgical procedure without any systemic spread. The diagnosis was made by histopathology and tissue fungal cultures. He was treated with incision and drainage followed by oral voriconazole for 4 weeks; which led to clinical recovery.


Assuntos
Aspergilose/diagnóstico , Aspergillus fumigatus/isolamento & purificação , Dermatomicoses/diagnóstico , Idoso de 80 Anos ou mais , Aspergilose/tratamento farmacológico , Dermatomicoses/tratamento farmacológico , Humanos , Imunocompetência , Masculino , Complicações Pós-Operatórias , Coloração e Rotulagem , Voriconazol/uso terapêutico
20.
Intern Med ; 59(9): 1189-1194, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32009092

RESUMO

Invasive tracheobronchial aspergillosis (ITBA) complicated by nontuberculous mycobacteria (NTM) is rare. An 88-year-old man was admitted for hemoptysis. Bronchoscopy revealed bronchial ulcers, and a tissue biopsy showed Aspergillus fumigatus. He was diagnosed with ITBA, which improved with voriconazole. During treatment, infiltrative shadows appeared in his lungs, and bronchoscopy was performed once again. A non-necrotic epithelioid granuloma and Mycobacterium intracellulare were detected in the biopsy specimen. He was diagnosed with NTM disease. It is important to note that tracheobronchial ulcers may cause hemoptysis and to identify the etiology and treat it appropriately when multiple bacteria are found.


Assuntos
Aspergilose/diagnóstico , Aspergillus fumigatus/isolamento & purificação , Broncopatias/diagnóstico , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Complexo Mycobacterium avium/isolamento & purificação , Úlcera/diagnóstico , Idoso de 80 Anos ou mais , Antifúngicos/uso terapêutico , Aspergilose/complicações , Aspergilose/tratamento farmacológico , Broncopatias/complicações , Broncopatias/tratamento farmacológico , Broncoscopia , Diagnóstico Diferencial , Humanos , Masculino , Infecções por Mycobacterium não Tuberculosas/complicações , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Úlcera/complicações , Úlcera/tratamento farmacológico , Voriconazol/uso terapêutico
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