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1.
Mycoses ; 66(6): 505-514, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36786491

RESUMO

BACKGROUND: To reduce the risk of invasive aspergillosis (IA), air purification by high-efficiency particulate air filtration and laminar air flow (HEPA/LAF) is standard of care in allogeneic blood stem cell transplantation. Its use in non-transplant haematological patients is inconsistent. OBJECTIVES: We sought to assess the incidence and outcome of pulmonary IA in non-transplant patients with life-threatening neutropenia by comparing an ambient air hospitalisation period (2008-2011) with a subsequent HEPA/LAF hospitalisation period (2012-2014). PATIENTS AND METHODS: We compared 204 consecutive patients with acute myeloid leukaemia, acute lymphoblastic leukaemia or aplastic anaemia completing 534 neutropenia-related hospitalisations under ambient air conditions with 126 such patients completing 437 neutropenia-related hospitalisations under HEPA/LAF conditions. IA was defined using the 2008 EORTC/MSG criteria. RESULTS: Within a 7-year study period, we observed one 'proven', three 'probable' and 73 'possible' IAs, most often during acute leukaemia remission induction. Their frequency rose with increasing duration of life-threatening neutropenia (1-10 days, 1.8%; >40 days, 35.2%) and concomitant severe anaemia (0 days, 3.2%; >20 days, 31.0%). Multiple logistic regression revealed a strong correlation between IA incidence and hospitalisation under HEPA/LAF conditions (odds ratio [OR], 0.368 [95% confidence interval, 0.207-0.654]; p < .001) and duration of neutropenia (OR, 1.043 [1.023-1.062] per day; p < .001) and anaemia (OR, 1.044 [1.008-1.081] per day; p = .016). IA-associated fatal outcomes were non-significantly reduced under HEPA/LAF (OR, 0.077 [0.005-1.151]; p = .063). The protective effect of HEPA/LAF was not seen under posaconazole prophylaxis (OR, 0.856 [0.376-1.950]; p = .711). CONCLUSIONS: Implementation of HEPA/LAF was associated with a significant reduction in neutropenia-related IA in non-transplant haematological patients.


Assuntos
Aspergilose , Hematologia , Aspergilose Pulmonar Invasiva , Leucemia Mieloide Aguda , Neutropenia , Humanos , Aspergilose/tratamento farmacológico , Neutropenia/complicações , Aspergilose Pulmonar Invasiva/etiologia , Aspergilose Pulmonar Invasiva/complicações , Leucemia Mieloide Aguda/complicações
2.
Mycopathologia ; 188(5): 731-743, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37040020

RESUMO

Invasive pulmonary aspergillosis remains a major cause of morbidity and mortality for immunocompromised children, particularly for patients with acute leukaemia and those undergoing haematopoietic stem cell transplantation. Timely diagnosis, using a combination of computed tomography (CT) imaging and microbiological testing, is key to improve prognosis, yet there are inherent challenges in this process. For CT imaging, changes in children are generally less specific than those reported in adults and recent data are limited. Respiratory sampling by either bronchoalveolar lavage or lung biopsy is recommended but is not always feasible in children, and serum biomarkers, including galactomannan, have important limitations. In this review we summarise the current paediatric data on available diagnostic tests for IPA and highlight key emerging diagnostic modalities with potential for future use.


Assuntos
Aspergilose Pulmonar Invasiva , Adulto , Humanos , Criança , Aspergilose Pulmonar Invasiva/diagnóstico , Aspergilose Pulmonar Invasiva/etiologia , Líquido da Lavagem Broncoalveolar/microbiologia , Biomarcadores , Prognóstico , Tomografia Computadorizada por Raios X/efeitos adversos , Mananas , Sensibilidade e Especificidade
3.
J Immunol ; 205(2): 480-488, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32522833

RESUMO

Aspergillus fumigatus is an environmental fungus that can cause invasive pulmonary aspergillosis when spores are inhaled into the respiratory tract and invade airway or lung tissue. Influenza is a common respiratory virus that can cause severe respiratory disease, and postinfluenza invasive pulmonary aspergillosis, which is becoming a well-recognized clinical problem, typically occurs in critically ill patients. Mice challenged with influenza A PR/8/34 H1N1 and subsequently challenged with A. fumigatus had increased fungal burden, viral burden, inflammation, and mortality compared with single infected mice. Neutrophil recruitment in the lung of superinfected mice was decreased; however, mice were not neutropenic, and there was no difference in absolute blood neutrophils between groups. Additionally, CXCL1 and CXCL2 were decreased in lungs of superinfected mice compared with controls. IFN levels were increased in mice that received influenza, and deletion of STAT1 resulted in decreased fungal burden, increased airway and lung neutrophils, and increased CXCL1 compared with wild-type mice, whereas deletion of STAT2 did not change fungal burden or airway neutrophilia compared with wild-type mice. These data demonstrate a mechanism by which influenza A-induced STAT1 signaling inhibits neutrophil recruitment and increases susceptibility to postinfluenza invasive pulmonary aspergillosis.


Assuntos
Aspergillus fumigatus/fisiologia , Vírus da Influenza A Subtipo H1N1/fisiologia , Influenza Humana/imunologia , Aspergilose Pulmonar Invasiva/imunologia , Pulmão/imunologia , Neutrófilos/imunologia , Infecções por Orthomyxoviridae/imunologia , Animais , Quimiocina CXCL1/metabolismo , Contagem de Colônia Microbiana , Progressão da Doença , Humanos , Evasão da Resposta Imune , Influenza Humana/complicações , Aspergilose Pulmonar Invasiva/etiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infiltração de Neutrófilos , Infecções por Orthomyxoviridae/complicações , Fator de Transcrição STAT1/metabolismo , Transdução de Sinais
4.
Infect Immun ; 89(4)2021 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-33495270

RESUMO

Toll-like receptors (TLRs) play a critical role in early immune recognition of Aspergillus, which can regulate host defense during invasive pulmonary Aspergillosis (IPA). However, the role of TLR7 in the pathogenesis of IPA remains unknown. In this study, an in vivo model of IPA was established to investigate the contribution of TLR7 to host anti-Aspergillus immunity upon invasive pulmonary Aspergillus fumigatus infection. The effects of TLR7 on phagocytosis and killing capacities of A. fumigatus by macrophages and neutrophils were investigated in vitro We found that TLR7 knockout mice exhibited lower lung inflammatory response and tissue injury, higher fungal clearance, and greater survival in an in vivo model of IPA compared with wild-type mice. TLR7 activation by R837 ligand led to wild-type mice being more susceptible to invasive pulmonary Aspergillus fumigatus infection. Macrophages, but not neutrophils, were required for the protection against IPA observed in TLR7 knockout mice. Mechanistically, TLR7 impaired phagocytosis and killing of A. fumigatus by macrophages but not neutrophils. Together, these data identify TLR7 as an important negative regulator of anti-Aspergillus innate immunity in IPA, and we propose that targeting TLR7 will be beneficial in the treatment of IPA.


Assuntos
Expressão Gênica , Interações Hospedeiro-Patógeno/imunologia , Imunidade Inata , Aspergilose Pulmonar Invasiva/etiologia , Macrófagos/imunologia , Macrófagos/metabolismo , Receptor 7 Toll-Like/genética , Animais , Biópsia , Citocinas/metabolismo , Modelos Animais de Doenças , Suscetibilidade a Doenças , Regulação da Expressão Gênica , Imunofenotipagem , Aspergilose Pulmonar Invasiva/metabolismo , Aspergilose Pulmonar Invasiva/patologia , Camundongos , Camundongos Knockout , Fagocitose/genética , Fagocitose/imunologia , Prognóstico , Receptor 7 Toll-Like/agonistas , Receptor 7 Toll-Like/deficiência , Receptor 7 Toll-Like/metabolismo
5.
Med Mycol ; 59(1): 110-114, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-32914189

RESUMO

Occurrence of putative invasive pulmonary aspergillosis was screened in 153 consecutive adult intensive care unit (ICU) patients with respiratory samples addressed for mycological diagnosis during a 6-week period at the emergence of coronavirus disease 2019 (COVID-19) pandemic. Positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) was observed for 106 patients (69.3%). Nineteen of them (17.9%) with positive Aspergillus results were considered as having putative invasive pulmonary aspergillosis. These observations underline the risk of pulmonary aspergillosis in COVID-19 patients, even in patients not previously known to be immunosuppressed, advocating active search for Aspergillus infection and prompt antifungal treatment. Standardized surveillance protocols and updated definitions for ICU putative invasive pulmonary aspergillosis are needed. LAY ABSTRACT: Adult ICU patients with respiratory samples addressed for mycological diagnosis were screened during the emergence of COVID-19 pandemic. Positive SARS-CoV-2 PCR was observed for 106 patients, nineteen of them (17.9%) having aspergillosis. This underlines the risk of aspergillosis in COVID-19 patients.


Assuntos
COVID-19/complicações , Estado Terminal , Aspergilose Pulmonar Invasiva/etiologia , SARS-CoV-2 , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade
6.
Med Mycol ; 59(8): 828-833, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-33724423

RESUMO

Invasive pulmonary aspergillosis (IPA) is a severe infection caused by aspergillus sp. that usually develops in patients with severe immunosuppression. IPA has been recently described in critically ill COVID-19 patients (termed as COVID-associated pulmonary aspergillosis, or CAPA) that are otherwise immunocompetent. In order to describe the characteristics of patients with CAPA, we conducted a retrospective cohort study in a tertiary care center in Mexico City. We included all patients with confirmed COVID-19 admitted to the intensive care unit that had serum or bronchoalveolar lavage galactomannan measurements. We used the criteria proposed by Koehler et al. to establish the diagnosis of CAPA. Main outcomes were the need for invasive mechanical ventilation (IMV) and in-hospital mortality. Out of a total of 83 hospitalized patients with COVID-19 in the ICU, 16 (19.3%) met the criteria for CAPA. All patients diagnosed with CAPA required IMV whereas only 84% of the patients in the non-IPA group needed this intervention (P = 0.09). In the IPA group, 31% (n = 5) of the patients died, compared to 13% (n = 9) in the non-CAPA group (P = 0.08). We conclude that CAPA is a frequent co-infection in critically ill COVID-19 patients and is associated with a high mortality rate. The timely diagnosis and treatment of IPA in these patients is likely to improve their outcome. LAY SUMMARY: We studied the characteristics of patients with COVID-19-associated invasive pulmonary aspergillosis (CAPA). Patients with CAPA tended to need invasive mechanical ventilation more frequently and to have a higher mortality rate. Adequate resources for its management can improve their outcome.


Assuntos
COVID-19/complicações , Aspergilose Pulmonar Invasiva/etiologia , SARS-CoV-2 , Adulto , Idoso , Feminino , Humanos , Aspergilose Pulmonar Invasiva/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Centros de Atenção Terciária
7.
Am J Respir Crit Care Med ; 202(5): 708-716, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32407157

RESUMO

Rationale: Invasive tracheobronchial aspergillosis (ITBA) is an uncommon but severe clinical form of invasive pulmonary aspergillosis in which the fungal infection is entirely or predominantly confined to the tracheobronchial tree.Objectives: To analyze the diagnostic and prognostic differences between tracheobronchial aspergillosis and pulmonary aspergillosis without tracheobronchial lesions among patients admitted to the ICU with severe influenza.Methods: This retrospective, observational study included critically ill patients with influenza associated with pulmonary aspergillosis from three hospital ICUs between 2010 and 2019. Patient characteristics and clinical and mycologic data at admission and during ICU stay were collected in a database to evaluate variables in the two groups.Measurements and Main Results: Thirty-five patients admitted to the ICU with severe influenza and pulmonary aspergillosis were included. Ten patients were included in the group with ITBA (n = 10 of 35; 28.6%), and 25 patients were included in the group without ITBA. The group with ITBA comprised more patients with active smoking, diabetes mellitus, and higher severity scores (Simplified Acute Physiology Score II). Ninety-day mortality rates in the groups with and without ITBA were 90% and 44%, respectively (P = 0.02). Moreover, significantly higher serum 1,3-ß-d-glucan and galactomannan and BAL fluid galactomannan concentrations were observed in the group with ITBA compared with the group without ITBA (P < 0.0001, P = 0.003, and P = 0.008, respectively).Conclusions: ITBA was associated with higher severity scores, mortality, and serum and BAL fluid galactomannan and 1,3-ß-d-glucan concentrations than invasive pulmonary aspergillosis without tracheobronchial lesions. ITBA should be systematically researched by bronchoscopic examination in ICU patients with concomitant pulmonary aspergillosis and influenza.Clinical trial registered with www.clinicaltrials.gov (NCT04077697).


Assuntos
Antifúngicos/uso terapêutico , Estado Terminal , Hospedeiro Imunocomprometido , Influenza Humana/complicações , Aspergilose Pulmonar Invasiva/etiologia , Idoso , Aspergillus/isolamento & purificação , Líquido da Lavagem Broncoalveolar/microbiologia , Feminino , Humanos , Unidades de Terapia Intensiva , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Aspergilose Pulmonar Invasiva/microbiologia , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença
8.
Mycoses ; 64(11): 1334-1345, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33934405

RESUMO

BACKGROUND: The diagnosis of invasive aspergillosis (IA) can be problematic in solid organ transplantation (SOT). The prognosis greatly varies according to the type of transplant, and the impact of prophylaxis is not well defined. PATIENTS AND METHODS: The Diaspersot cohort analyses the impact of IA in SOT in Spain during the last 10 years. Proven and probable/putative IA was included. RESULTS: We analysed 126 cases of IA. The incidences of IA were as follows: 6.5%, 2.9%, 1.8% and 0.6% for lung, heart, liver and kidney transplantation, respectively. EORTC/MSG criteria confirmed only 49.7% of episodes. Tree-in-bud sign or ground-glass infiltrates were present in 56.3% of patients, while serum galactomannan (optical density index >0.5) was positive in 50.6%. A total of 41.3% received combined antifungal therapy. Overall mortality at 3 months was significantly lower (p < 0.001) in lung transplant recipients (14.8%) than in all other transplants [globally: 48.6%; kidney 52.0%, liver 58.3%, heart 31.2%, and combined 42.9%]. Fifty-four percent of episodes occurred despite the receipt of antifungal prophylaxis, and in 10%, IA occurred during prophylaxis (breakthrough infection), with both nebulised amphotericin (in lung transplant recipients) and candins (in the rest). CONCLUSIONS: Invasive aspergillosis diagnostic criteria, applied to SOT patients, may differ from those established for haematological patients. IA in lung transplants has a higher incidence, but is associated with a better prognosis than other transplants. Combination therapy is frequently used for IA in SOT. Prophylactic measures require optimisation of its use within this population.


Assuntos
Aspergilose Pulmonar Invasiva/diagnóstico , Aspergilose Pulmonar Invasiva/terapia , Transplante de Órgãos , Adulto , Antifúngicos/efeitos adversos , Antifúngicos/uso terapêutico , Causalidade , Estudos de Coortes , Feminino , Humanos , Aspergilose Pulmonar Invasiva/epidemiologia , Aspergilose Pulmonar Invasiva/etiologia , Masculino , Estudos Retrospectivos , Sensibilidade e Especificidade , Espanha/epidemiologia , Voriconazol/efeitos adversos , Voriconazol/uso terapêutico , Adulto Jovem
9.
Mycoses ; 64(2): 132-143, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33210776

RESUMO

OBJECTIVES: Information on the recently COVID-19-associated pulmonary aspergillosis (CAPA) entity is scarce. We describe eight CAPA patients, compare them to colonised ICU patients with coronavirus disease 2019 (COVID-19), and review the published literature from Western countries. METHODS: Prospective study (March to May, 2020) that included all COVID-19 patients admitted to a tertiary hospital. Modified AspICU and European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria were used. RESULTS: COVID-19-associated pulmonary aspergillosis was diagnosed in eight patients (3.3% of 239 ICU patients), mostly affected non-immunocompromised patients (75%) with severe acute respiratory distress syndrome (ARDS) receiving corticosteroids. Diagnosis was established after a median of 15 days under mechanical ventilation. Bronchoalveolar lavage was performed in two patients with positive Aspergillus fumigatus cultures and galactomannan (GM) index. Serum GM was positive in 4/8 (50%). Thoracic CT scan findings fulfilled EORTC/MSG criteria in one case. Isavuconazole was used in 4/8 cases. CAPA-related mortality was 100% (8/8). Compared with colonised patients, CAPA subjects were administered tocilizumab more often (100% vs. 40%, p = .04), underwent longer courses of antibacterial therapy (13 vs. 5 days, p = .008), and had a higher all-cause mortality (100% vs. 40%, p = .04). We reviewed 96 similar cases from recent publications: 59 probable CAPA (also putative according modified AspICU), 56 putative cases and 13 colonisations according AspICU algorithm; according EORTC/MSG six proven and two probable. Overall, mortality in the reviewed series was 56.3%. CONCLUSIONS: COVID-19-associated pulmonary aspergillosis must be considered a serious and potentially life-threatening complication in patients with severe COVID-19 receiving immunosuppressive treatment.


Assuntos
COVID-19/complicações , Aspergilose Pulmonar Invasiva/etiologia , Aspergillus fumigatus/fisiologia , COVID-19/virologia , Humanos , Aspergilose Pulmonar Invasiva/diagnóstico , Aspergilose Pulmonar Invasiva/microbiologia , Aspergilose Pulmonar Invasiva/mortalidade , Estudos Prospectivos , SARS-CoV-2/fisiologia
10.
Mycoses ; 64(2): 144-151, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33217071

RESUMO

BACKGROUND: As the global coronavirus pandemic (COVID-19) spreads across the world, new clinical challenges emerge in the hospital landscape. Among these challenges, the increased risk of coinfections is a major threat to the patients. Although still in a low number, due to the short time of the pandemic, studies that identified a significant number of hospitalised patients with COVID-19 who developed secondary fungal infections that led to serious complications and even death have been published. OBJECTIVES: In this scenario, we aim to determine the prevalence of invasive fungal infections (IFIs) and describe possible associated risk factors in patients admitted due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. PATIENTS/METHODS: We designed an open prospective observational study at the Rey Juan Carlos University Hospital (Mostoles, Spain), during the period from February 1 to April 30, 2020. RESULTS: In this article, we reported seven patients with COVID-19-associated pulmonary aspergillosis (CAPA) who had a poor prognosis. Severely ill patients represent a high-risk group; therefore, we must actively investigate the possibility of aspergillosis in all of these patients. Larger cohort studies are needed to unravel the role of COVID-19 immunosuppressive therapy as a risk factor for aspergillosis. CONCLUSIONS: As the pandemic continues to spread across the world, further reports are needed to assess the frequency of emergent and highly resistant reemergent fungal infections during severe COVID-19. These coinfections are leading a significant number of patients with COVID-19 to death due to complications following the primary viral disease.


Assuntos
COVID-19/complicações , Aspergilose Pulmonar Invasiva/etiologia , Infecções Oportunistas/microbiologia , Adulto , Idoso , Aspergillus/genética , Aspergillus/isolamento & purificação , Aspergillus/fisiologia , COVID-19/virologia , Feminino , Hospitalização , Humanos , Instituições para Cuidados Intermediários/estatística & dados numéricos , Aspergilose Pulmonar Invasiva/microbiologia , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/etiologia , Prevalência , Estudos Prospectivos , SARS-CoV-2/fisiologia , Espanha
11.
Eur J Clin Microbiol Infect Dis ; 39(8): 1543-1550, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32279121

RESUMO

Invasive pulmonary aspergillosis (IPA) is a high mortality opportunistic infection among kidney transplant recipients. This study assessed the risk factors and outcomes of IPA after KT. A retrospective study was conducted at a tertiary-care referral hospital in Korea. Electronic medical records of patients diagnosed with IPA after KT between February 1995 and March 2015 were reviewed. The control patients comprised two patients who received KT before and after each IPA case. Twenty-six cases were diagnosed with IPA among 1963 recipients at a median of 58 years old. The most common cause of end-stage renal disease was diabetic nephropathy. The median time to diagnosis was 161 days. Delayed graft function was associated with the development of IPA. The overall 12-week mortality rate of IPA was 57.5%. Serum GM level ≥ 2 and BAL GM level ≥ 5 were associated with 12-week mortality in the Kaplan-Meier survival analyses. Approximately half of IPA in KT recipients developed during the late posttransplant period (> 6 months), especially after treatment for acute rejection. Careful monitoring for IPA is required in patients with delayed graft function, DM, and who received rejection therapy. Higher serum and BAL GM were associated with 12-week mortality.


Assuntos
Aspergilose Pulmonar Invasiva/epidemiologia , Transplante de Rim , Adulto , Antifúngicos/uso terapêutico , Estudos de Casos e Controles , Feminino , Humanos , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Aspergilose Pulmonar Invasiva/etiologia , Aspergilose Pulmonar Invasiva/mortalidade , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco
12.
Mycopathologia ; 185(6): 1077-1084, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33009966

RESUMO

Although patients with severe immunodeficiency and hematological malignancies has been considered at highest risk for invasive fungal infection, patients with severe pneumonia due to influenza, and severe acute respiratory syndrome coronavirus (SARS-CoV) are also at a higher risk of developing invasive pulmonary aspergillosis (IPA). Recently, reports of IPA have also emerged among SARS-CoV-2 infected patients admitted to intensive care units (ICUs). Here, we report a fatal case of probable IPA in an acute myeloid leukemia patient co-infected with SARS-CoV-2 and complicated by acute respiratory distress syndrome (ARDS). Probable IPA is supported by multiple pulmonary nodules with ground glass opacities which indicate halo sign and positive serum galactomannan results. Screening studies are needed to evaluate the prevalence of IPA in immunocompromised patients infected with SARS-CoV-2. Consequently, testing for the presence of Aspergillus in lower respiratory secretions and galactomannan in consecutive serum samples of COVID-19 patients with timely and targeted antifungal therapy based on early clinical suspicion of IPA are highly recommended.


Assuntos
COVID-19/complicações , COVID-19/mortalidade , Aspergilose Pulmonar Invasiva/etiologia , Aspergilose Pulmonar Invasiva/mortalidade , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/mortalidade , SARS-CoV-2/patogenicidade , Adulto , COVID-19/sangue , Evolução Fatal , Feminino , Galactose/análogos & derivados , Humanos , Irã (Geográfico) , Leucemia Mieloide Aguda/sangue , Mananas/sangue
13.
Clin Transplant ; 33(9): e13544, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30900296

RESUMO

These updated AST-IDCOP guidelines provide information on epidemiology, diagnosis, and management of Aspergillus after organ transplantation. Aspergillus is the most common invasive mold infection in solid-organ transplant (SOT) recipients, and it is the most common invasive fungal infection among lung transplant recipients. Time from transplant to diagnosis of invasive aspergillosis (IA) is variable, but most cases present within the first year post-transplant, with shortest time to onset among liver and heart transplant recipients. The overall 12-week mortality of IA in SOT exceeds 20%; prognosis is worse among those with central nervous system involvement or disseminated disease. Bronchoalveolar lavage galactomannan is preferred for the diagnosis of IA in lung and non-lung transplant recipients, in combination with other diagnostic modalities (eg, chest CT scan, culture). Voriconazole remains the drug of choice to treat IA, with isavuconazole and lipid formulations of amphotericin B regarded as alternative agents. The role of combination antifungals for primary therapy of IA remains controversial. Either universal prophylaxis or preemptive therapy is recommended in lung transplant recipients, whereas targeted prophylaxis is favored in liver and heart transplant recipients. In these guidelines, we also discuss newer antifungals and diagnostic tests, antifungal susceptibility testing, and special patient populations.


Assuntos
Antifúngicos/uso terapêutico , Aspergillus/isolamento & purificação , Aspergilose Pulmonar Invasiva/diagnóstico , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Transplante de Órgãos/efeitos adversos , Guias de Prática Clínica como Assunto/normas , Humanos , Aspergilose Pulmonar Invasiva/etiologia , Sociedades Médicas , Transplantados
14.
Clin Transplant ; 33(8): e13641, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31211850

RESUMO

OBJECTIVE: The purpose of our study was to evaluate the diagnostic value of serum galactomannan antigen (GM) testing combined with chest computed tomography (CT) of invasive pulmonary aspergillosis (IPA) in pediatric patients after hematopoietic stem cell transplantation. METHODS: A retrospective nested case-control study was conducted in the identifying IPA among pediatric patients. RESULTS: A total of 141 eligible pediatric recipients with febrile neutropenia were enrolled in this study. All patients in the cases were diagnosed with proven-probable IPA(PP-IPA), while only 9 patients in the controls. GM testing was positive in 38 pediatric recipients in the cases and nine recipients in the controls with sensitivity of 62.3%, specificity of 81.8%. Among all patients with IPA, 46 patients in the cases and 9 patients in the controls had typical features of CT imaging with sensitivity of 79.3%, specificity of 85.2%. For discrimination of participants' GM testing combined with CT evaluation, the AUC of the diagnostic model was 0.887 with PPV of 0.764, and NPV of 0.872. Sensitivity was 0.793, and specificity was 0.852 in IPA. CONCLUSION: The combination methods with serum GM and CT scan might be used as a valuable marker for early diagnosis of IPA in pediatric patients after HSCT.


Assuntos
Biomarcadores/sangue , Diagnóstico Precoce , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Aspergilose Pulmonar Invasiva/diagnóstico , Mananas/sangue , Radiografia Torácica/métodos , Tomografia Computadorizada por Raios X/métodos , Adolescente , Aspergillus/isolamento & purificação , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Seguimentos , Galactose/análogos & derivados , Humanos , Lactente , Recém-Nascido , Aspergilose Pulmonar Invasiva/sangue , Aspergilose Pulmonar Invasiva/diagnóstico por imagem , Aspergilose Pulmonar Invasiva/etiologia , Masculino , Prognóstico , Estudos Retrospectivos
15.
J Infect Chemother ; 25(9): 731-734, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30905630

RESUMO

Recently, basidiomycete Schizophyllum commune has been reported as a cause of allergic bronchopulmonary mycosis. However, it is rare as a cause of otitis externa. We experienced a very rare case of otitis externa caused by S. commune in a 68-year-old man with a history of chronic otitis media. We performed Gram staining at the first consultation and follow-up treatment and found fungal cells on the smear and treated him with an appropriate antifungal drug. The results of identification and antifungal susceptibility testing obtained in cooperation with clinical microbiologists at other facilities was very important for future treatment planning decisions. Medical practitioners worldwide should introduce a Gram staining tool into their workflow and cooperate closely with clinical microbiologists to achieve antimicrobial stewardship.


Assuntos
Aspergilose Pulmonar Invasiva/etiologia , Otite Externa/microbiologia , Otite Média/complicações , Schizophyllum/isolamento & purificação , Idoso , Antifúngicos/uso terapêutico , Gestão de Antimicrobianos , Violeta Genciana , Humanos , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Aspergilose Pulmonar Invasiva/microbiologia , Masculino , Fenazinas
16.
Monaldi Arch Chest Dis ; 89(2)2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31107037

RESUMO

Invasive Aspergillus tracheobronchitis is a relatively rare form of invasive pulmonary aspergillosis characterized by invasion of the tracheobronchial tree by Aspergillus spp. Invasive pulmonary aspergillosis is predominantly detected in severely immunocompromised patients. Notably however, pulmonary and tracheobronchial cases of invasive aspergillosis have also been reported, particularly in the context of severe malaria caused by Plasmodium falciparum. Herein, we present a case of invasive Aspergillus tracheobronchitis in a patient with hairy cell leukemia and previous Plasmodium falciparum infection.


Assuntos
Bronquite/microbiologia , Aspergilose Pulmonar Invasiva/etiologia , Leucemia de Células Pilosas/complicações , Malária Falciparum/complicações , Traqueíte/microbiologia , Evolução Fatal , Humanos , Aspergilose Pulmonar Invasiva/complicações , Masculino , Pessoa de Meia-Idade
17.
Am J Transplant ; 18(9): 2352-2355, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29790292

RESUMO

Invasive aspergillosis (IA) affects the lungs and disseminates mostly in patients with neutropenia and/or patients who are receiving immunosuppressive and steroid therapies. Despite progress in the diagnosis of and therapy for IA, it is still characterized by a high mortality rate. Currently, voriconazole is considered as the standard therapy for IA. Over recent years, triazole-resistant Aspergillus fumigatus isolates have emerged in the environment due to the use of fungicidal agricultural products, with the risk of developing IA related to a resistant isolate. However, resistance may also develop in patients who are undergoing long-term triazole therapy, particularly in the setting of chronic forms of pulmonary aspergillosis. Herein we describe a kidney transplant recipient who failed to respond to voriconazole therapy due to acquired resistance secondary to the appearance of a de novo mutation (Y121F) in the cyp51A gene during chronic necrotizing pulmonary aspergillosis. The infecting isolate acquired voriconazole resistance in 8 months despite plasma concentrations within the recommended range of the drug, necessitating lobectomy in association with a new antifungal strategy consisting of liposomal amphotericin and caspofungin with a good outcome over 36 months.


Assuntos
Antifúngicos/uso terapêutico , Aspergillus fumigatus/efeitos dos fármacos , Farmacorresistência Fúngica/efeitos dos fármacos , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Transplante de Rim/efeitos adversos , Voriconazol/farmacologia , Idoso , Anfotericina B/uso terapêutico , Caspofungina/uso terapêutico , Sistema Enzimático do Citocromo P-450/genética , Proteínas Fúngicas/genética , Humanos , Aspergilose Pulmonar Invasiva/etiologia , Aspergilose Pulmonar Invasiva/patologia , Masculino , Mutação , Prognóstico
18.
BMC Infect Dis ; 18(1): 648, 2018 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-30541477

RESUMO

BACKGROUND: Liver transplant recipients are at high risk of developing invasive aspergillosis and in particular by Aspergillus fumigatus which is the most commonly encountered species in this population. Other non-fumigatus Aspergillus species with reduced susceptibility to antifungal drugs can also be involved. Accurate identification associated to antifungal susceptibility testing is essential for therapy adjustment. We report a case of invasive pulmonary aspergillosis due to Aspergillus pseudodeflectus in a liver transplant recipient. To our knowledge, this is the first reported case of invasive aspergillosis due to this species with a reduced susceptibility to azoles. CASE PRESENTATION: A 64 year-old woman with drug-induced fulminant hepatitis underwent liver transplantation. Prophylactic treatment with caspofungin was introduced due to aspergillosis risk factors consisting in hemodialysis and fulminant hepatitis. Six weeks after transplantation, CT scan showed a right pulmonary opacity associated with an increase of galactomannan (index 5.4). Culture of BAL grew with several colonies of Aspergillus sp. The diagnosis of invasive aspergillosis was probable according to the EORTC criteria. The antifungal susceptibility tests (Etest®) revealed low MICs to echinocandins and amphotericin B) but high MICs to azoles. After these results, voriconazole was switched to liposomal amphotericin B. The patient died one month after diagnosis from a refractory septic shock with multiple organ failure. A molecular identification of isolate, based on partial ß-tubulin and calmodulin genes, was performed and identified A. pseudodeflectus. CONCLUSIONS: Our case raises the question of pathogenicity of this species, which belongs to Aspergillus section Usti and is genetically and morphologically very close to Aspergillus calidoustus that was previously reported in human transplant recipients.


Assuntos
Aspergilose/diagnóstico , Aspergillus/isolamento & purificação , Transplante de Fígado/efeitos adversos , Fígado/microbiologia , Transplantados , Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Aspergilose/etiologia , Aspergilose/microbiologia , Aspergillus/genética , Aspergillus/patogenicidade , Equinocandinas/uso terapêutico , Feminino , Humanos , Aspergilose Pulmonar Invasiva/diagnóstico , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Aspergilose Pulmonar Invasiva/etiologia , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Voriconazol/uso terapêutico
19.
Mycoses ; 61(11): 861-867, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30015364

RESUMO

There is a paucity of data regarding mixed mold pulmonary infections (MMPIs) in patients with haematological malignancies with or without haematopoietic stem cell transplantation (HSCT). We retrospectively studied 27 such patients (2005-2015) and compared them to patients with invasive pulmonary aspergillosis (IPA) caused by Aspergillus fumigatus. Factors associated with the diagnosis of MMPIs were significant corticosteroid use [20 (74%) vs 6 (22%), P < 0.001], sputum as the source specimen [13 (48%) vs 3 (11%), P = 0.003], younger age (median age: 58 vs 66 years, P = 0.006), and male sex [22 (81%) vs 13 (48%), P = 0.01]. Haematological cancers other than acute myeloid leukaemia (AML)/myelodysplastic syndromes (MDS) were less common in MMPIs than in IPA patients [AML/MDS: 6 (22%) vs 14 (52%), P = 0.04]. Only significant corticosteroid use [95% CI (2.7-42.7), P < 0.001], and sputum as the source specimen [95% (1.6-41.6), P = 0.012] were statistically significant as independently associated with increased risk of MMPIs diagnosis in multivariate analysis. Total mortality rate at day 42 postdiagnosis was comparable in both groups.


Assuntos
Neoplasias Hematológicas/cirurgia , Aspergilose Pulmonar Invasiva/microbiologia , Complicações Pós-Operatórias/microbiologia , Adolescente , Adulto , Idoso , Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/genética , Aspergillus fumigatus/isolamento & purificação , Aspergillus fumigatus/fisiologia , Feminino , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/microbiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Aspergilose Pulmonar Invasiva/diagnóstico , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Aspergilose Pulmonar Invasiva/etiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Atenção Terciária à Saúde/estatística & dados numéricos , Adulto Jovem
20.
Rev Chil Pediatr ; 89(2): 241-245, 2018 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-29799893

RESUMO

INTRODUCTION: Mycotic infections due to Aspergillus spp, are the main mycotic associated infections in liver transplant patients, with mortality rates up to 90% of the cases. Almost 50% of patients will de velop an infection during the first months after transplantation, of which 10% are associated with op portunistic agents. OBJECTIVE: To describe the diagnosis and management of an Invasive Pulmonary Aspergillosis (IPA) episode in a liver transplant patient. CASE REPORT: 11-months-old patient with liver transplant due to a biliary atresia who developed severe pneumonia associated with mechanical ventilation. The bronchoalveolar lavage showed high levels of galactomannan and positive culture for Aspergillus fumigatus leading to an IPA diagnosis. This episode was treated with antifungal with a favorable outcome. CONCLUSION: The IPA is an opportunistic infection in liver transplant patients, with high mortality rates, that must be suspected in this group of patients since an early diagnosis and treatment reduce mortality.


Assuntos
Aspergilose Pulmonar Invasiva/diagnóstico , Transplante de Fígado , Complicações Pós-Operatórias/diagnóstico , Antifúngicos/uso terapêutico , Feminino , Humanos , Lactente , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Aspergilose Pulmonar Invasiva/etiologia , Complicações Pós-Operatórias/tratamento farmacológico
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