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1.
Medicine (Baltimore) ; 99(6): e18938, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32028403

RESUMO

RATIONALE: Behçet's disease (BD) is an inflammatory disease that leads to multisystemic immune dysfunction and that involves pulmonary system alterations. PATIENT CONCERNS: A 26-year-old woman presented with dull right chest pain for 30 days and intermittent cough with expectoration for 5 days. She had a history of recurrent oral ulcer and constitutional rash 2 months prior. DIAGNOSES: The patient was diagnosed with BD complicated by IPA and Aspergillus auriculatus infection. INTERVENTIONS: The patient was administered itraconazole oral solution (200 mg b.i.d) to treat the fungal infection. After a diagnosis of BD was made, she received 40 mg of methylprednisolone sodium succinate daily for 1 week.Then, she also received 24 mg of methylprednisolone sodium succinate daily, which was decreased by 2 mg per half month, until the rash had resolved. The patient continued to receive 200 mg Q. D itraconazole orally for 3 months. Thereafter, itraconazole was stopped, while daily oral administration of 10 mg of methylprednisolone sodium succinate was continued. OUTCOMES: The rash was observed to resolve, and CT revealed that the lesions in both the right and left lung were reduced. During a telephone follow-up performed after 6 months, the patient stated that no symptoms had recurred during the follow-up period. LESSONS: This case illustrates that for patients with BD, ignoring extrapulmonary symptoms often leads to a delayed diagnosis. Physicians should perform a thorough medical history and physical examination of these patients, as the information obtained in this manner may provide important clues for disease diagnosis and treatment.


Assuntos
Aspergillus/isolamento & purificação , Síndrome de Behçet/diagnóstico , Aspergilose Pulmonar Invasiva/diagnóstico , Adulto , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Síndrome de Behçet/complicações , Síndrome de Behçet/tratamento farmacológico , Dor no Peito/etiologia , Tosse/etiologia , Diagnóstico Diferencial , Quimioterapia Combinada , Feminino , Humanos , Aspergilose Pulmonar Invasiva/complicações , Aspergilose Pulmonar Invasiva/diagnóstico por imagem , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Itraconazol/administração & dosagem , Itraconazol/uso terapêutico , Metilprednisolona/administração & dosagem , Metilprednisolona/uso terapêutico , Tomografia Computadorizada por Raios X
2.
Rev Med Suisse ; 15(666): 1795-1801, 2019 Oct 09.
Artigo em Francês | MEDLINE | ID: mdl-31599520

RESUMO

Aspergillus is a group of molds which is found everywhere worldwide, exposition of human being is common. Most of immunocompetent people do not develop disease caused by Aspergillus. However, diseases in different forms may occur in certain conditions in immunocompetent patient. These diseases include hypersensitivity reactions, like allergic broncho-pulmonary aspergillosis, or infectious process like chronic pulmonary aspergillosis or invasive pulmonary aspergillosis. This article reviewed the clinical features of these diseases and the current available diagnostic techniques.


Assuntos
Imunocompetência/imunologia , Aspergilose Pulmonar/diagnóstico , Aspergilose Pulmonar/imunologia , Aspergilose Broncopulmonar Alérgica/diagnóstico , Aspergilose Broncopulmonar Alérgica/imunologia , Humanos , Aspergilose Pulmonar Invasiva/diagnóstico , Aspergilose Pulmonar Invasiva/imunologia
3.
Rev Port Cardiol ; 38(7): 497-501, 2019 07.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31495716

RESUMO

INTRODUCTION: Infection remains a major complication among heart transplant (HT) recipients, causing approximately 20% of deaths in the first year after transplantation. In this population, Aspergillus spp. can have various clinical presentations including invasive pulmonary aspergillosis (IPA), with high mortality (53-78%). OBJECTIVES: To establish the characteristics of IPA infection in HT recipients and their outcomes in our center. METHODS: Among 328 HTs performed in our center between 1998 and 2016, we identified five cases of IPA. Patient medical records were examined and clinical variables were extracted. RESULTS: All cases were male, and mean age was 62 years. The most common indication for HT was non-ischemic dilated cardiomyopathy. Productive cough was reported as the main symptom. The radiological assessment was based on chest X-ray and chest computed tomography. The most commonly reported radiographic abnormality was multiple nodular opacities in both techniques. Bronchoscopy was performed in all patients and Aspergillus fumigatus was isolated in four cases on bronchoalveolar lavage culture. Treatment included amphotericin in four patients, subsequently changed to voriconazole in three, and posaconazole in one patient, with total treatment lasting an average of 12 months. Neutropenia was found in only one patient, renal failure was observed in two patients, and concurrent cytomegalovirus infection in three patients. All patients were alive after a mean follow-up of 18 months. CONCLUSIONS: IPA is a potentially lethal complication after HT. Early diagnosis and prompt initiation of aggressive treatment are the cornerstone of better survival.


Assuntos
Transplante de Coração/efeitos adversos , Aspergilose Pulmonar Invasiva/mortalidade , Complicações Pós-Operatórias/mortalidade , Transplantados , Idoso , Seguimentos , Humanos , Aspergilose Pulmonar Invasiva/diagnóstico , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Estudos Retrospectivos , Fatores de Risco , Espanha/epidemiologia , Taxa de Sobrevida/tendências , Tomografia Computadorizada por Raios X
4.
Clin Lab ; 65(8)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31414743

RESUMO

BACKGROUND: We report an invasive pulmonary aspergillosis (IPA) with negative (1,3)-ß-D-glucan and dynamically elevated white blood cells combined with procalcitonin proven by bronchoalveolar lavage fluid (BALF) culture. METHODS: Appropriate laboratory tests are carried out. Chest CTs were performed to assess the lungs. The cause of infection was determined using BALF culture. RESULTS: Serum (1,3)-ß-D-glucan was negative, white blood cells and procalcitonin were significantly higher than normal. The bronchoscopy revealed obvious necrotic detritus and pseudo membrane in the trachea, left and right main bronchi, and branches. BALF culture revealed the presence of Aspergillus. CONCLUSIONS: Negative (1,3)-ß-D-glucan is not safe to rule out invasive pulmonary aspergillosis. BALF culture is critical for IPA diagnosis.


Assuntos
Líquido da Lavagem Broncoalveolar/microbiologia , Complicações do Diabetes/diagnóstico , Aspergilose Pulmonar Invasiva/diagnóstico , Pneumonia/diagnóstico , Pró-Calcitonina/sangue , beta-Glucanas/sangue , Aspergillus/isolamento & purificação , Aspergillus/fisiologia , Complicações do Diabetes/sangue , Complicações do Diabetes/microbiologia , Diagnóstico Diferencial , Humanos , Aspergilose Pulmonar Invasiva/complicações , Aspergilose Pulmonar Invasiva/microbiologia , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Pneumonia/complicações , Pneumonia/microbiologia
5.
Mycoses ; 62(10): 945-948, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31313395

RESUMO

BACKGROUND: Invasive pulmonary aspergillosis (IPA) remains a life-threatening opportunistic infection, but can be difficult to diagnose. New biomarkers are therefore needed. Gliotoxin (GT), a secondary metabolite of Aspergillus fumigatus, and bis(methylthio)gliotoxin (bmGT), a degradation product of GT, have been proposed as potential biomarkers. However, these findings have yet to be confirmed. OBJECTIVES: To identify the diagnostic potential of GT and bmGT in serum and bronchoalveolar lavage fluid (BALf) in haematology patients compared to galactomannan (GM). MATERIALS AND METHODS: We prospectively collected culture supernatant, serum and BALf from patients with culture-positive IPA and measured GT and bmGT concentrations using ultra high-performance liquid chromatography-quadrupole time of flight mass spectrometry. Galactomannan was detected using a commercially available enzyme immunoassay. RESULTS: We included 18 patients with proven (n = 6) and probable (n = 12) IPA, all with positive cultures for Aspergillus fumigatus. BmGT was only detected in serum from one patient (5.6%), whereas GM was positive (optical density ≥ 0.5) in 11/18 patients (61.1%, P = 0.002). We could not find GT in any serum sample. In BALf, bmGT was detected in 8/18 patients (44.4%) and GT in 9/18 patients (50%), compared to GM (optical density ≥ 1.0) in all patients (100%). CONCLUSIONS: Gliotoxin and bis(methylthio)gliotoxin had a very poor performance for diagnosing IPA. As other biomarkers are more sensitive and easier to detect, we would not recommend serum or BALf GT/bmGT to be used in the diagnosis of IPA.


Assuntos
Biomarcadores/sangue , Testes Diagnósticos de Rotina/métodos , Gliotoxina/sangue , Aspergilose Pulmonar Invasiva/diagnóstico , Líquido da Lavagem Broncoalveolar/química , Humanos , Mananas/sangue , Estudos Prospectivos , Soro/química
6.
Clin Lab ; 65(6)2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31232022

RESUMO

BACKGROUND: Invasive pulmonary aspergillosis and nocardia overlap in clinical and radiological presentations, so differentiating between nocardia and invasive pulmonary aspergillosis is confusing. Though sputum culture could distinguish between nocardia and aspergillus fumigatus, but for the ultimate diagnosis, sputum culture provided limited help. Here we report a case of a patient with positive G test and aspergillus fumigatus sputum culture mimic invasive pulmonary aspergillosis ultimately diagnosed as nocardia through bronchoalveolar lavage culture combined metagenomic next-generation sequencing (NGS). METHODS: Bronchoalveolar lavage culture combined metagenomic NGS for infectious diseases were performed for diagnosis. RESULTS: Bronchoalveolar lavage culture combined metagenomic next-generation sequencing showed Nocardia Gelsenkirchen. CONCLUSIONS: Positive G test and sputum culture were not specific, while bronchoalveolar lavage culture and NGS gave more information for a differential diagnosis between nocardia and aspergillus fumigatus.


Assuntos
Aspergillus fumigatus/isolamento & purificação , Aspergilose Pulmonar Invasiva/diagnóstico , Nocardiose/diagnóstico , Nocardia/isolamento & purificação , Escarro/microbiologia , beta-Glucanas/sangue , Aspergillus fumigatus/genética , Aspergillus fumigatus/fisiologia , Líquido da Lavagem Broncoalveolar/microbiologia , Diagnóstico Diferencial , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Aspergilose Pulmonar Invasiva/microbiologia , Teste do Limulus , Pulmão/microbiologia , Pessoa de Meia-Idade , Nocardia/genética , Nocardia/fisiologia , Nocardiose/microbiologia , Sensibilidade e Especificidade
7.
Mycoses ; 62(8): 673-679, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31177621

RESUMO

Autopsy studies show that IA is among the most commonly missed diagnoses in critically ill patients. And, because of lack of unequivocal diagnostic criteria, a timely diagnosis remains challenging. We investigate the epidemiology of and the clinical risk factors for IA in critically ill patients. We conducted a retrospective, observational study of all consecutive ICU patients with evidence of IA in the postmortem examination. During the period of the study (25 years), 893 postmortem examinations were performed in the ICU. Twenty-five patients (2.8%) were diagnosed with IA in autopsy. Only ten (40%) were classified as IA ante-mortem, based on the initiation of antifungal treatment. The most common comorbid conditions were corticosteroid treatment (n = 14, 56%), chronic obstructive pulmonary disease (COPD) (n = 11, 44%), immunosuppression (n = 6, 24%) and haematological malignancy (n = 5, 20%). Twenty-three patients (92%) had three or more risk factors for IA. Critically ill patients with pulmonary infiltrates, treated with high doses intravenous corticosteroids (even for a short period of time), particularly COPD patients who developed worsening respiratory insufficiency despite appropriate treatment were at the highest risk of IA.


Assuntos
Autopsia , Estado Terminal , Unidades de Terapia Intensiva , Aspergilose Pulmonar Invasiva/epidemiologia , Aspergilose Pulmonar Invasiva/mortalidade , Idoso , Antifúngicos/uso terapêutico , Comorbidade , Feminino , Humanos , Aspergilose Pulmonar Invasiva/diagnóstico , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Espanha
9.
Mycoses ; 62(8): 651-658, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31066092

RESUMO

Invasive aspergillosis (IA) is a serious hazard to haematological and critical care patients. Impactful risk factors for developing IA have been characterised; however, systematic analysis of baseline prognostic factors for treatment course of IA is missing. To understand prognostic variables, we analysed original articles identifying baseline factors that predict treatment outcome in patients with IA. PubMed database was searched for publications since database inception until May 2018. Inclusion criteria were published baseline prognostic factors present at the diagnosis of IA. In total, 58 studies from 267 centres reported 7320 patients with IA and 40 different predictors. Unfavourable predictors in medical history were kidney (7.4%, 10/136) and liver failure (3.7%, 5/136), ICU admission (3.7%, 5/136) and uncontrolled underlying disease (3.7%, 5/136). Regarding state of immunosuppression, negative outcome predictors were prolonged neutropenia (12.5%, 17/136), corticosteroid treatment (8.1%, 11/136) and graft-vs-host disease (3.7%, 5/136). On the pathogen side, relevant predictors were galactomannan positivity (8.1%, 11/136), Aspergillus terreus infection (2.2%, 3/136) and lack of amphotericin B susceptibility (1.5%, 2/136). IA-specific predictors were disseminated disease (5.1%, 7/136) and CNS involvement (2.9%, 4/136). Imaging results associated with negative outcome were multiple consolidations (2.9%, 4/136), bipulmonary lesions (2.2%, 3/136) and pleural effusion (2.2%, 3/136). At diagnosis of IA, most frequently identified predictors of outcome were neutropenia, corticosteroid use, elevated galactomannan, renal failure and disseminated disease. The predictors may be used to identify patients at high risk for treatment failure and to stratify neglected patient groups for clinical trials.


Assuntos
Aspergillus/patogenicidade , Aspergilose Pulmonar Invasiva/diagnóstico , Adulto , Antifúngicos/uso terapêutico , Doença Enxerto-Hospedeiro/complicações , Humanos , Imunossupressão/efeitos adversos , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Mananas/metabolismo , Neutropenia/complicações , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Falha de Tratamento , Resultado do Tratamento
10.
Mycoses ; 62(7): 576-583, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31034703

RESUMO

False positivity of antigen immunoassays used as an early diagnostic tool to detect invasive fungal infections is known. Interpretation of the assay needs the identification of sources which could affect the specificity of the test. We focused on the influence of parenteral nutrition (PN) and piperacillin-tazobactam (TZP) on fungal immunoassays. Measurable amounts of Candida antigen mannan were detected in several compounds of PN and TZP in a previous in vitro study. In the current study, 84 patients undergoing allogeneic haematopoietic cell transplantation receiving either TZP, PN or both were monitored with Aspergillus and Candida antigen assay. Six patients were analysed closer in a kinetic analysis with more frequent blood sampling to detect mannan. PN in diverse compositions as well as TZP did not increase significantly the amount of mannan and the Aspergillus antigen in serum. We could not confirm the positive results of the in vitro study. Physicians should be aware that mannan antigenemia due to drug infusion could be a transient issue and should be considered in the interpretation of fungal immunoassays, although we could not find clinically relevant effects on mannan levels.


Assuntos
Antibacterianos/administração & dosagem , Antígenos de Fungos/sangue , Candidíase Invasiva/diagnóstico , Reações Falso-Positivas , Aspergilose Pulmonar Invasiva/diagnóstico , Nutrição Parenteral , Combinação Piperacilina e Tazobactam/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Transplante Homólogo/efeitos adversos , Adulto Jovem , Inibidores de beta-Lactamases/administração & dosagem
11.
Med Mycol ; 57(Supplement_2): S94-S103, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30816963

RESUMO

Invasive aspergillosis (IA) incidence is increasing in several countries like France, and numerous cases are indeed missed and still only diagnosed at autopsy as evidenced by recently published data. Such missed diagnoses are obviously encountered when appropriate diagnostic tools are not available especially in low resource areas or when biologists have not been trained enough in medical mycology (i.e., microscopic examination and culture in most of those areas). Besides logistical issues, which are indeed critical, IA may not be recognized because clinicians failed to consider that risk factors are evolving with the IA burden now observed among patients with chronic lymphoid malignancies or receiving new biotherapies, with diabetes mellitus or liver cirrhosis and/or acute alcoholic hepatitis, with patients from the intensive care unit (ICU) and among patients with some predisposing primary immune deficiencies now reaching the adult's age. This is also the case for human immunodeficiency virus (HIV)-infected patients who failed to meet the classical definitions of IA. From the radiology perspective, new entities of IA have also emerged which absolutely need to be recognized especially bronchial-based-IA among allogeneic stem cell transplant recipients. Finally, from the laboratory side, contribution and limits of indirect blood biomarkers should be integrated to the clinical life in order not to miss IA cases. To conclude, several diagnostic tools should be combined and a constant dialog between laboratory and clinics is crucial to appropriately diagnose IA.


Assuntos
Testes Diagnósticos de Rotina/métodos , Hospedeiro Imunocomprometido , Aspergilose Pulmonar Invasiva/diagnóstico , Aspergilose Pulmonar Invasiva/epidemiologia , França/epidemiologia , Humanos , Incidência , Fatores de Risco
12.
Med Mycol ; 57(Supplement_2): S155-S160, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30816965

RESUMO

Aspergillosis is more common among immunocompromised patients with neutropenia or immunosuppression due to corticosteroid use, and infections are typically of the lung or sinuses. For diagnosis, broncholaveolar lavages (BALs) and lung biopsies are the specimens of choice. Culture and microscopic examinations are a must have and laboratory results should immediately be reported to the clinic. Fungal elements (hyphae) display the proof of an infection if present in primarily steril specimens, independent of culture results. Microscopy should be performed preferably using optical brighteners and histopathology using Gomori's methenamine silver stain or Periodic acid-Schiff. Serum and BAL galactomannan assays are recommended as markers for the diagnosis of invasive aspergillosis, PCR should be considered in conjunction with other diagnostic tests. Antifungal treatment decreases GM sensitivity. Pathogen identification to species complex level is strongly recommended for all clinically relevant Aspergillus isolates.


Assuntos
Aspergillus/isolamento & purificação , Testes Diagnósticos de Rotina/métodos , Aspergilose Pulmonar Invasiva/diagnóstico , Aspergillus/química , Aspergillus/citologia , Aspergillus/genética , Biópsia , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/microbiologia , Histocitoquímica , Humanos , Pulmão/microbiologia , Pulmão/patologia , Mananas/análise , Técnicas Microbiológicas , Microscopia , Reação em Cadeia da Polimerase
13.
J Infect Chemother ; 25(7): 547-551, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30824299

RESUMO

Aspergillus fumigatus is the commonest cause of pulmonary aspergillosis; however, a recently developed molecular genetic technique identified A. lentulus as a sibling species. Most of the isolates were found in solid organ recipients, often associated with a fatal outcome. Moreover, there is concern that A. lentulus has low susceptibility to multiple antifungal agents. Herein, we report an adult immunocompromised patient with proven invasive pulmonary aspergillosis (IPA) caused by A. lentulus, which was identified through molecular genetic analysis. The patient was diagnosed with IPA by bronchoscopy 3 weeks after initiating systemic corticosteroid therapy for anti-neutrophil cytoplasmic antibody-associated vasculitis. The clinical course of IPA due to A. lentulus showed improvement after treatment with the antifungal agent voriconazole. In summary, we report an adult immunocompromised patient without a history of transplantation who was diagnosed with IPA due to A. lentulus successfully treated with voriconazole, and we also report the findings of a literature review on IPA caused by A. lentulus.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Aspergillus/patogenicidade , Glucocorticoides/efeitos adversos , Aspergilose Pulmonar Invasiva/microbiologia , Idoso de 80 Anos ou mais , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Antifúngicos/uso terapêutico , Aspergillus/isolamento & purificação , Broncoscopia , Evolução Fatal , Feminino , Humanos , Hospedeiro Imunocomprometido , Aspergilose Pulmonar Invasiva/diagnóstico , Aspergilose Pulmonar Invasiva/imunologia , Pulmão/diagnóstico por imagem , Pulmão/microbiologia , Tomografia Computadorizada por Raios X , Voriconazol/uso terapêutico
14.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(3): 331-335, 2019 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-30914095

RESUMO

OBJECTIVE: To evaluate the accuracy and diagnostic value of bronchoalveolar lavage fluid galactomannan test (BALF-GM) combined with serum GM test on invasive pulmonary aspergillosis (IPA). METHODS: 190 cases of BALF-GM and 4 787 cases of serum GM specimens suspected of fungal infection in patients admitted to Affiliated Hospital of Jining Medical University from January 2016 to June 2018 were enrolled and analyzed. All patients were classified into clinically confirmed IPA, clinically diagnosed IPA, suspected IPA and excluded IPA according to the classification standard of Expert consensus on diagnosis and treatment of pulmonary mycosis. The coincidence rate of BALF and serum GM test results with clinical diagnosis was analyzed. Receiver operating characteristic (ROC) curve was performed, and the diagnostic value of BALF and serum GM test alone or in combination for IPA was evaluated. Subgroup analysis was performed in patients with normal or abnormal immune function, and the sensitivity and specificity of BALF and serum GM test were compared separately or jointly. RESULTS: The positive rate of BALF-GM was 46.8% (89/190), and 10.4% (497/4 787) on serum GM. Among them, 156 patients were both tested on BALF and serum GM. There were 44 cases with both positive in BALF and serum GM, the coincidence rate of clinical definite was 93.2% (41/44). There were 34 cases with positive BALF-GM and negative GM test in serum, and the coincidence rate of clinical definite was 64.7% (22/34). There were 56 cases positive in serum GM and negative in BALF-GM, and the coincidence rate of clinical definite was 48.2% (27/56). BALF and serum GM tests were both negative in 22 cases, and the coincidence rate of exclusion diagnosis was 90.9% (20/22). ROC curve analysis showed that the diagnostic value of BALF-GM test combined with serum GM test for IPA was better than that of BALF-GM test or serum GM test alone [area under ROC curve (AUC): 0.992 vs. 0.983, 0.976]. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 95.3%, 87.0%, 93.2% and 90.9%, respectively. Subgroup analysis showed that among 89 patients with positive BALF-GM test, 85 cases (95.5%) had normal immune function and 4 cases (4.5%) had unknown condition. Among 497 patients with positive serum GM test, 12 cases (2.4%) had normal immune function, 372 cases (74.9%) had abnormal immune function and 113 cases (22.7%) were uncertain. It was shown by ROC curve analysis that the sensitivity of positive BALF-GM test in diagnosis of IPA in patients with normal immune function was higher than that of positive serum GM test (95.6% vs. 88.9%), while the sensitivity of positive serum GM test in patients with abnormal immune function was higher than that of positive BALF-GM test (91.8% vs. 89.9%). CONCLUSIONS: The results of BALF and serum GM tests are in good agreement with clinical diagnosis, and the combined detection of BALF and serum GM is more valuable for IPA diagnosis than single detection, especially for patients with unknown immune function.


Assuntos
Líquido da Lavagem Broncoalveolar/química , Aspergilose Pulmonar Invasiva/diagnóstico , Mananas/análise , Humanos , Mananas/sangue , Sensibilidade e Especificidade
15.
Int J Infect Dis ; 83: 20-25, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30926540

RESUMO

BACKGROUND: This study aimed to evaluate the diagnostic role of PCR detection of Aspergillus DNA in the broncho-alveolar lavage (BAL) fluid in a large cohort of patients suspected to have invasive pulmonary aspergillosis (IPA). METHODS: Consecutive immunocompromised patients who underwent bronchoscopy with BAL sampling and PCR detection of Aspergillus DNA for the diagnosis of pulmonary infiltrates were included in the study. Galactomannan (GM) antigen testing in BAL and serum and BAL fungal culture were also performed. Patients were classified as having IPA (proven/probable/possible) or no-IPA according to the EORTC/MSG diagnostic criteria. RESULTS: During 12 years (2005-2016), 1248 bronchoscopies were performed for 1072 patients. 77% had hematological malignancy, of them 40% had AML and 35.6% underwent HSCT. IPA was diagnosed in 531 patients (42.5%), 7-proven, 280-probable and 244-possible. PCR was positive in 266 cases, of them 213 had IPA, indicating a true positive rate of 80% (213/266) and a false positive rate of 20% (53/266). These results establish the diagnostic performance of PCR to have sensitivity of 40%, specificity of 93%, PPV- 80% and NPV-68%. Of 244 patients with possible IPA, 80 had positive PCR. Including PCR in the diagnostic criteria would move 80 cases from the possible group to the probable one. A combination of positive PCR and/or BAL-GM increases sensitivity to 74%, while positivity of both tests elevates PPV to 99.4%. CONCLUSIONS: Inclusion PCR for the detection of Aspergillus-DNA in BAL in the mycological criteria of the EORTC/MSG definitions increases the rate and the certainty of IPA diagnosis.


Assuntos
Líquido da Lavagem Broncoalveolar/microbiologia , Aspergilose Pulmonar Invasiva/diagnóstico , Reação em Cadeia da Polimerase/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , DNA Fúngico/análise , Feminino , Humanos , Hospedeiro Imunocomprometido , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
17.
Med Mycol ; 57(8): 987-996, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30753590

RESUMO

Diagnosis of invasive aspergillosis (IA) is challenging, particularly in high-risk patients with lung lesions other than typical according to 2008-EORTC/MSG criteria. Even if microbiology is positive, they still remain unclassified according to 2008-EORTC/MSG. Quantitative polymerase chain reaction (qPCR) provides new mycological documentation of IA. This retrospective study assessed Aspergillus fumigatus real time qPCR (MycoGENIE®) in BAL to diagnose IA and identify azole-resistant strains. Clinical, radiological, and microbiological data from 114 hematology patients (69% HSCT recipients; 29% on mould active agents) from years 2012-2017 were collected; and 123 BAL samples were tested with qPCR (cutoff: Ct < 40) and galactomannan (GM, Platelia®, cutoff: 0.5 ODI). Patients were classified as proven/probable, possible, and no-IA. "Atypical-IA" referred to patients with lesions other than typical according to 2008-EORTC/MSG and positive mycology. Proven IA was diagnosed in two cases (1.6%), probable in 28 (22.8%), possible in 27 (22%), atypical in 14 (11.4%). qPCR was positive in 39 samples (31.7%). Sensitivity and specificity of qPCR for proven/probable IA (vs no-IA; atypical-IA excluded) were 40% (95% confidence interval [CI]: 23-59) and 69% (95%CI: 55-81), respectively. Sensitivity of qPCR was higher when combined with GM (83%, 95%CI: 65-94) and in those receiving mould-active agents at BAL (61%, 95%CI: 32-86). One sample had TR34/L98H mutation. In conclusion, in high-risk hematology patients with various lung lesions, A. fumigatus qPCR in BAL contributes to diagnosing IA, particularly if combined with GM and in patients receiving mould-active agents might allow detecting azole-resistant mutations in culture negative samples.


Assuntos
Aspergillus fumigatus/isolamento & purificação , Análise Química do Sangue/métodos , Líquido da Lavagem Broncoalveolar/microbiologia , Aspergilose Pulmonar Invasiva/diagnóstico , Mananas/sangue , Técnicas de Diagnóstico Molecular/métodos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Neoplasias Hematológicas/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Fatores de Tempo , Adulto Jovem
18.
Mycoses ; 62(3): 230-236, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30565352

RESUMO

BACKGROUND: We compared new Aspergillus Galactomannan Lateral Flow Assay with the newly formatted Aspergillus-specific Lateral Flow device tests for the diagnosis of invasive pulmonary aspergillosis (IPA) in non-neutropenic patients. METHODS: We performed both tests in 82 bronchoalveolar lavage fluid samples from 82 patients at risk for IPA but without underlying haematologic malignancy. Samples were collected between September 2016 and September 2018 at the University of California San Diego, United States. IPA was classified following two published consensus criteria. RESULTS: Classification of cases varied widely between the two consensus criteria. When using criteria established for the intensive care unit, 26/82 patients (32%) met criteria for proven or putative IPA. Both point-of-care assays showed sensitivities ranging between 58% and 69%, with specificities between 68% and 75%. Sensitivity increased up to 81% when both tests were combined. CONCLUSION: The study outlines the need for updated, unified and more broadly applicable consensus definitions for classifying IPA in non-neutropenic patients, a work that is currently in progress. Both point-of-care tests showed comparable performance, with sensitivities and specificities in the 60%-70% range when used alone and increasing to 80% when used in combination. The new point-of-care tests may serve a role at the bedside in those with clinical suspicion of IPA.


Assuntos
Líquido da Lavagem Broncoalveolar/química , Imunoensaio/métodos , Aspergilose Pulmonar Invasiva/diagnóstico , Mananas/análise , Sistemas Automatizados de Assistência Junto ao Leito , Adulto , Idoso , Idoso de 80 Anos ou mais , California , Feminino , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Adulto Jovem
19.
Mycopathologia ; 184(1): 181-185, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30101407

RESUMO

The widespread use of T lymphocyte-associated antigen-4 (CTLA-4) and programmed death (PD)-1 and PD ligand-1 (PDL1)-targeted agents in cancer patients as immunotherapy has raised some issues on their safety profile. Regarding infectious complications, it has emerged that these compounds do not intrinsically increase susceptibility to opportunistic infections, which mainly correlate with the co-administration of systemic immunosuppressive therapy (high-dose corticosteroids and anti-tumor necrosis factors inhibitors) to cure immune-related adverse events (colitis, hepatitis, pneumonitis and pancreatitis), well-known complications of these targeted drugs. These observations lead experts' opinion to suggest primary anti-Pneumocystis prophylaxis in patients undergoing CTLA-4 and PD-1/PDL1 agents who will receive prednisone 20 mg daily for ≥ 4 weeks. Few data on invasive fungal infections in this context are available. We report here a case of probable invasive pulmonary aspergillosis (p-IPA) complicating first-line immunotherapy with pembrolizumab for metastatic lung cancer that was further aggravated by multidrug-resistant Pseudomonas aeruginosa superinfection of fungal cavities; the patient received concurrent systemic corticosteroid therapy as anti-edema treatment for cerebral metastases. Reviewing literature about Aspergillus diseases in subjects receiving CTLA-4 and PD-1 and PDL1-targeted agents, we found three cases of invasive aspergillosis and one case of exacerbation of chronic progressive pulmonary aspergillosis after nivolumab treatment; to the best of our knowledge, this is the first report of p-IPA complicating pembrolizumab immunotherapy. Briefly, in this new setting of biological/targeted drugs, waiting for growing clinical experience, we recommend a high level of alertness in diagnosing any infectious complications.


Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/secundário , Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Aspergilose Pulmonar Invasiva/diagnóstico , Infecções por Pseudomonas/diagnóstico , Adenocarcinoma de Pulmão/complicações , Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Farmacorresistência Bacteriana Múltipla , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Aspergilose Pulmonar Invasiva/complicações , Aspergilose Pulmonar Invasiva/patologia , Pessoa de Meia-Idade , Infecções por Pseudomonas/complicações , Infecções por Pseudomonas/patologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/isolamento & purificação
20.
Mycopathologia ; 184(1): 151-154, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30168076

RESUMO

Aspergillus terreus may colonize the airways of patients with cystic fibrosis (CF). Whether this merits antifungal treatment is still unclear due to heterogeneous reports regarding its pathogenic potential. Although allergic manifestations are documented, invasive aspergillosis (IA) caused by A. terreus has not been described. We present here one case of probable IA caused by A. terreus, highlighting its role as an emerging agent of IA in CF patients. Voriconazole was effective, and the patient was healthy after 12 weeks of treatment. Serial determination of serum galactomannan level and periodic cultures from respiratory specimens may help in monitoring CF patients by identifying such pathogens. Further studies on the fungal species colonizing the CF airways are warranted, especially in India. This case report suggests A. terreus as a potential agent of IA which should not be ignored, particularly in this patient group.


Assuntos
Aspergillus/isolamento & purificação , Fibrose Cística/complicações , Aspergilose Pulmonar Invasiva/diagnóstico , Aspergilose Pulmonar Invasiva/patologia , Antifúngicos/administração & dosagem , Aspergillus/classificação , Criança , Monitoramento de Medicamentos , Humanos , Índia , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Aspergilose Pulmonar Invasiva/microbiologia , Masculino , Mananas/sangue , Resultado do Tratamento , Voriconazol/administração & dosagem
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