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1.
Medicine (Baltimore) ; 98(41): e17535, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593129

RESUMO

Scedosporium genus as a significant emerging opportunist causes a broad spectrum of disease in not only immunosuppressed but also immunocompetent patients. The lung is one of the most commonly encountered sites of Scedosporium infection. Due to its very high levels of antifungal resistance, surgery has been recommended as an important part in the treatment of pulmonary Scedosporium spp infection, even in immunocompetent cases. However, whether lung surgery could help to reduce the risk of death in immunocompetent patients is not clear.We retrospectively retrieved the records of pulmonary infections with Scedosporium species in immunocompetent patients through a comprehensive literature search. The association of surgery on all-cause mortality was explored using binary logistic regression (BLR). Receiver operating characteristic (ROC) curve analysis was carried out to evaluate the capability of the model.The comprehensive searching strategy yielded 33 case reports and 3 case series in total, with 40 individual patients being included. The overall mortality was 12.50%. The fatality rate was 9.09% (2/22) in cases with surgery and 16.67% (3/18) in cases without surgery (odds ratio, 0.50; 95% confidence interval, 0.07-3.38; P = .48). Consistently, BLR analysis identified no statistical association between surgery and reduced mortality (odds ratio, 1.19; 95% confidence interval, 0.09-15.64; P = .89), after adjusting for age, gender, and antifungal chemotherapy. The area under the ROC curve was 0.88.For immunocompetent patients with pulmonary Scedosporium spp infection, surgical therapy may not be associated with reduced mortality. Surgical excision could be considered but is not imperative in this group of patients.


Assuntos
Pneumopatias Fúngicas/tratamento farmacológico , Pneumopatias Fúngicas/cirurgia , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/cirurgia , Scedosporium/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/uso terapêutico , Farmacorresistência Fúngica/fisiologia , Feminino , Humanos , Hospedeiro Imunocomprometido/efeitos dos fármacos , Pneumopatias Fúngicas/microbiologia , Pneumopatias Fúngicas/mortalidade , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Micoses/tratamento farmacológico , Micoses/epidemiologia , Micoses/microbiologia , Micoses/mortalidade , Estudos Observacionais como Assunto , Cuidados Pós-Operatórios , Infecções Respiratórias/microbiologia , Infecções Respiratórias/mortalidade , Estudos Retrospectivos , Scedosporium/isolamento & purificação , Voriconazol/administração & dosagem , Voriconazol/uso terapêutico
2.
Infection ; 46(4): 503-512, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29748841

RESUMO

PURPOSE: Little is known about risk factors for the outcome of pulmonary mucormycosis. We summarized characteristics of this rare disease, and systemically explored risk factors for the outcome. METHODS: Ninety-two patients with pulmonary mucormycosis, including 12 patients at Peking Union Medical College Hospital and 80 patients published in 62 articles between 2006 and 2016, were retrospectively analyzed. RESULTS: The median age was 47.5 years, and the male to female ratio was 2.8:1. Hematological disorders, diabetes mellitus, renal insufficiency and organ transplantation were main underlying conditions. Twelve percent of patients had no underlying diseases. A predilection for involvement of upper lobes was noted, and thick-walled cavity was described in 37.0% of patients on chest computed tomography. Most of the patients were diagnosed by microscopic analysis (95.7%), mainly histopathology; and only a minority were diagnosed by culture of sterile materials (28.3%). The overall mortality rate was 30.4%. Four independent determinants were associated with a better prognosis: hemoptysis (adjusted OR 7.910; 95% CI 1.411-44.342), chronic onset (adjusted OR 25.269, 95% CI 1.654-385.993), treated with medicine (adjusted OR 53.896, 95% CI 3.072-945.561), and treated with surgery (adjusted OR 5.983, 95% CI 1.497-23.918). CONCLUSIONS: Pulmonary mucormycosis is a rare infection with a high mortality. Invasive approach for histopathology and culture are crucial for a definite diagnosis. Acute onset patients had a poorer prognosis, and early treatment with antifungal therapy is imperative. Surgical approach is recommended in appropriate patients for a better outcome.


Assuntos
Pneumopatias Fúngicas/diagnóstico , Pneumopatias Fúngicas/microbiologia , Mucormicose/diagnóstico , Mucormicose/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/uso terapêutico , Biópsia , Criança , Terapia Combinada , Comorbidade , Gerenciamento Clínico , Feminino , Humanos , Pneumopatias Fúngicas/mortalidade , Pneumopatias Fúngicas/terapia , Masculino , Pessoa de Meia-Idade , Mucormicose/mortalidade , Mucormicose/terapia , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Avaliação de Sintomas , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto Jovem
3.
Heart Lung ; 47(3): 261-263, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29622277

RESUMO

BACKGROUND: Severe coccidioidal pneumonia with acute respiratory distress syndrome (ARDS) is associated with high mortality. Extracorporeal membrane oxygenation (ECMO) has been applied successfully to other severe fungal pneumonia associated with ARDS. We review our experience with the use of ECMO in severe coccidioidal ARDS. OBJECTIVES: To review indications and outcome of ECMO in severe pulmonary coccidioidomycosis. METHODS: Three cases of severe ARDS caused by coccidioidomycosis are presented. All were managed with ECMO. Clinical course, complications, antifungal therapy and outcome are reviewed. RESULTS: Three cases of severe coccidioidal ARDS survived after treatment with ECMO. Common complications included bacterial pneumonia, encephalopathy and critical illness myopathy. They received liposomal amphotericin during ECMO, and transitioned to azole therapy. All required prolonged hospitalization and rehabilitation. CONCLUSIONS: ECMO was life-saving in cases of coccidioidal ARDS. Common complications included pneumonia, encephalopathy and critical illness myopathy. All cases were successfully managed with liposomal amphotericin followed by azole therapy. They required prolonged hospitalization and rehabilitation.


Assuntos
Coccidioidomicose , Oxigenação por Membrana Extracorpórea , Pneumopatias Fúngicas , Síndrome do Desconforto Respiratório do Adulto , Coccidioidomicose/epidemiologia , Coccidioidomicose/mortalidade , Coccidioidomicose/terapia , Humanos , Pneumopatias Fúngicas/epidemiologia , Pneumopatias Fúngicas/mortalidade , Pneumopatias Fúngicas/terapia , Síndrome do Desconforto Respiratório do Adulto/epidemiologia , Síndrome do Desconforto Respiratório do Adulto/mortalidade , Síndrome do Desconforto Respiratório do Adulto/terapia
4.
Exp Clin Transplant ; 16 Suppl 1(Suppl 1): 122-125, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29528008

RESUMO

OBJECTIVES: Pulmonary infections are a significant cause of morbidity and mortality in solid-organ transplant recipients despite enhanced facilities for perioperative care. The aim of this study was to evaluate the demographic characteristics, clinical course, and outcomes of renal transplant recipients with pneumonia. MATERIALS AND METHODS: The medical records of all renal transplant recipients from January 2010 to December 2014 were retrospectively reviewed, and patients diagnosed with pneumonia according to Centers for Disease Control and Prevention criteria were evaluated. Pneumonia was classified as community acquired or nosocomial. Patient demographics, microbiologic findings, need for intensive care/mechanical ventilation over the course of treatment, and information about clinical follow-up and mortality were all recorded. RESULTS: Eighteen (13.4%) of 134 renal transplant recipients had 25 pneumonia episodes within the study period. More than half (56%) of the pneumonia episodes developed within the first 6 months of transplant, whereas 44% developed after 6 months (all > 1 year). Eight cases (32%) were considered nosocomial pneumonia, and 17 (68%) were considered community-acquired pneumonia. Bacteria were the most common cause of pneumonia (28%), and fungi ranked second (8%). No viral or mycobacterial agents were detected. No patients required prolonged mechanical ventilation. No statistically significant difference was found in the need for intensive care or regarding mortality between patients with nosocomial and community-acquired pneumonia. Two patients (11%) died, and all remaining patients recovered. CONCLUSIONS: The present study confirmed that pneumonia after renal transplant is not a rare complication but a significant cause of morbidity. Long-term and close follow-up for pneumonia is necessary after renal transplant.


Assuntos
Infecções Comunitárias Adquiridas/microbiologia , Infecção Hospitalar/microbiologia , Transplante de Rim/efeitos adversos , Pneumopatias Fúngicas/microbiologia , Pneumonia Bacteriana/microbiologia , Adolescente , Adulto , Idoso , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/mortalidade , Infecções Comunitárias Adquiridas/terapia , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/mortalidade , Infecção Hospitalar/terapia , Feminino , Humanos , Incidência , Transplante de Rim/mortalidade , Pneumopatias Fúngicas/diagnóstico , Pneumopatias Fúngicas/mortalidade , Pneumopatias Fúngicas/terapia , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/diagnóstico , Pneumonia Bacteriana/mortalidade , Pneumonia Bacteriana/terapia , Prevalência , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Turquia/epidemiologia , Adulto Jovem
5.
Clin Respir J ; 12(2): 499-509, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27614086

RESUMO

INTRODUCTION: The important role of radiological examinations of invasive pulmonary aspergillosis (IPA) in patients with neutropenia has been well studied; however, little is known about IPA in critically ill chronic obstructive pulmonary disease (COPD) patients. OBJECTIVES: To evaluate the value of radiological examinations in the diagnosis and prognosis of invasive bronchial-pulmonary aspergillosis (IBPA) in critically ill COPD patients. METHODS: We included 61 critically ill COPD patients in the intensive care unit (ICU) in a retrospective, single-center cohort study. RESULTS: All of the patients were classified as IBPA group (n = 21) or non-IBPA group (n = 40). The chest computed tomography (CT) image analysis showed that the IBPA group had the highest percent of patchiness (76.2%), followed by multiple nodules (33.3%), angio-invasive patterns (including halo sign, wedge consolidation and air-crescent sign/cavity with a relatively low percent of 19%, 19% and 28.5%, respectively), and the multiple nodules that were distributed along the airway provided the most specific image, with the highest specificity of 92.5%. Compared to the survivors in the IBPA group, non-surviving patients had a higher percent of large consolidation (0% vs. 45.5%, P = .035). When the new effusions appeared on a chest x-ray (CXR), the creatinine (140.4 µmol/L vs. 64.0 µmol/L, P = .010) and PaO2 /FiO2 (188 mm Hg vs. 222 mm Hg, P = .034) rate deteriorated. CONCLUSIONS: Multiple nodules that were distributed along with broncho-vascular bundles were relatively common and specific in critically ill COPD patients with IBPA. Deteriorated CXR combined with specific laboratory examinations, even when appropriate antibiotics were used, could indicate a diagnosis of IBPA. Large consolidations might be considered as poor prognostic indicators.


Assuntos
Aspergilose Pulmonar Invasiva/diagnóstico por imagem , Aspergilose Pulmonar Invasiva/microbiologia , Pneumopatias Fúngicas/diagnóstico por imagem , Pneumopatias Fúngicas/microbiologia , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Radiografia/métodos , Idoso , Idoso de 80 Anos ou mais , Aspergillus/isolamento & purificação , Estudos de Casos e Controles , Estado Terminal/mortalidade , Feminino , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Aspergilose Pulmonar Invasiva/mortalidade , Pneumopatias Fúngicas/mortalidade , Pneumopatias Fúngicas/patologia , Masculino , Nódulos Pulmonares Múltiplos/patologia , Prognóstico , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/patologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
6.
Clin Transplant ; 31(11)2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28871606

RESUMO

BACKGROUND: Prospective studies to determine associated risk factors and related outcomes for pulmonary fungal infection (PFI) after pediatric lung transplant (PLT) are lacking. METHODS: NIH-sponsored Clinical Trials in Organ Transplantation in Children enrolled PLT candidates, collecting data prospectively for 2 years post-transplant. Demographics, signs/symptoms, radiology, pathology and microbiology were collected. Analyses evaluated for PFI-related risks and outcomes. RESULTS: In 59 PLT, pre-transplant fungal colonization occurred in 6 donors and 15 recipients. Cystic fibrosis (CF) was associated with pre-transplant colonization (P < .01). Twenty-five (42%) PLT had 26 post-transplant colonizations (median = 67 days, range = 0-750 days) with Candida (13), Aspergillus (4), mold (6) or yeast (3). Post-PLT colonization was not associated with CF, age, or pre-PLT colonization. Thirteen PFIs occurred in 10 (17%) patients, 3 proven (Candida species) and 10 probable (Candida [3], Aspergillus [3], Penicillium [3], and mold [1]). Pulmonary fungal infection was preceded by post-PLT colonization with the same organism in 4 of 13 PFI, but post-PLT colonization did not predict subsequent PFI (P = .87). Older age at transplant was a risk for PFI (P < .01). No mortality was attributed to PFI. Prophylaxis use was not associated with decreased post-PLT colonization (P = .60) or PFI (P = .48). CONCLUSION: In PLT, PFI and fungal colonization are common but without associated mortality. Post-PLT colonization did not predict PFI. Optimal prevention strategies require additional study.


Assuntos
Fibrose Cística/complicações , Rejeição de Enxerto/mortalidade , Pneumopatias Fúngicas/mortalidade , Transplante de Pulmão/efeitos adversos , Complicações Pós-Operatórias/mortalidade , Adolescente , Criança , Fibrose Cística/microbiologia , Fibrose Cística/cirurgia , Feminino , Seguimentos , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Estudos Longitudinais , Pneumopatias Fúngicas/etiologia , Masculino , Prognóstico , Estudos Prospectivos , Fatores de Risco
7.
Exp Clin Transplant ; 15(5): 547-553, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28697720

RESUMO

OBJECTIVES: Pneumonia has a negative effect on the outcome of liver transplant. Our aim was to analyze early-onset pneumonia that developed within the first month after transplant. MATERIALS AND METHODS: This prospective single-center study included 56 adult living-donor liver transplant recipients; those who developed early-onset pneumonia based on clinical and radiologic criteria were investigated as to causative pathogens and then followed up and compared with other recipients without pneumonia to illustrate risk factors, outcomes, and related mortality of posttransplant pneumonia. RESULTS: Twelve patients (21.4%) developed early-onset pneumonia with mortality rate of 75% (9 of 12). Sixteen pathogens were isolated; extended spectrum beta-lactamase producing Enterobacteriaceae were the most common (31.2%) followed by carbapenem-producing Enterobacteriaceae and methicillin-resistant Staphylococcus aureus (18.8%). Fungi were isolated in 3 cases that were also coinfected with bacteria. Diabetes mellitus (P = .042), liberal postoperative fluid therapy (P = .028), prolonged posttransplant intensive care unit stay (P = .01), atelectasis grade ≥ 2 (P ≤ .001), and calcineurin inhibitor-induced neurotoxicity (P = .04) were risk factors for early posttransplant pneumonia. CONCLUSIONS: Pneumonia is the leading cause of early mortality after liver transplant. The emergence of multidrug-resistant bacteria is major issue associated with a high rate of treatment failure.


Assuntos
Transplante de Fígado/efeitos adversos , Pneumopatias Fúngicas/microbiologia , Pneumonia Bacteriana/microbiologia , Adulto , Antibacterianos/uso terapêutico , Antifúngicos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Farmacorresistência Fúngica Múltipla , Egito/epidemiologia , Feminino , Hospitais Universitários , Humanos , Incidência , Transplante de Fígado/mortalidade , Doadores Vivos , Pneumopatias Fúngicas/diagnóstico , Pneumopatias Fúngicas/tratamento farmacológico , Pneumopatias Fúngicas/mortalidade , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/diagnóstico , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/mortalidade , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
8.
Mycopathologia ; 182(11-12): 1101-1109, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28660464

RESUMO

Fonsecaea spp. are melanized fungi which cause most cases of chromoblastomycosis. The taxonomy of this genus has been revised, now encompassing four species, with different pathogenic potential: F. pedrosoi, F. nubica, F. pugnacius, and F. monophora. The latter two species present wider clinical spectrum and have been associated with cases of visceral infection, most often affecting the brain. To our knowledge, this is the first report of proven case of F. monophora respiratory tract infection. A Brazilian 57-year-old-female patient underwent kidney transplantation on January 12, 2013. On the fourth postoperative month, the patient presented with fever, productive cough, and pleuritic pain in the right hemithorax. A thoracic CT scan showed a subpleural 2.2-cm nodular lesion in the right lung lower lobe, with other smaller nodules (0.5-0.7 cm) scattered in both lungs. Bronchoscopy revealed a grayish plaque on the right bronchus which was biopsied. Microscopic examination demonstrated invasion of bronchial mucosa by pigmented hyphae. Culture from the bronchial biopsy and bronchoalveolar lavage samples yielded a melanized mold, which was eventually identified as F. monophora. She started treatment with voriconazole (400 mg q.12h on the first day, followed by 200 mg q.12h). After 4 weeks of therapy, voriconazole dose was escalated to 200 mg q.8h and associated with amphotericin B (deoxycolate 1 mg/kg/day) because of a suspected dissemination to the brain. The patient eventually died of sepsis 8 weeks after the start of antifungal therapy. In conclusion, F. monophora may cause respiratory tract infection in solid organ transplant recipients.


Assuntos
Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Ascomicetos/isolamento & purificação , Transplante de Rim/efeitos adversos , Pneumopatias Fúngicas/tratamento farmacológico , Voriconazol/uso terapêutico , Ascomicetos/classificação , Ascomicetos/genética , Brasil , DNA Espaçador Ribossômico/genética , Feminino , Humanos , Pneumopatias Fúngicas/microbiologia , Pneumopatias Fúngicas/mortalidade , Pessoa de Meia-Idade , Toxoplasma/isolamento & purificação , Toxoplasmose Cerebral/diagnóstico , Toxoplasmose Cerebral/tratamento farmacológico , Toxoplasmose Cerebral/microbiologia
9.
Expert Rev Anti Infect Ther ; 15(1): 23-32, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27771978

RESUMO

INTRODUCTION: Ventilator-associated pneumonia (VAP) is a distinct clinical entity characterized by an onset after 48 hours of the application of mechanical ventilation (MV). Protocols exist to aid in the prevention of VAP, but this infection carries a devastating impact on patient morbidity and potentially mortality. Areas covered: In this review we present key concepts from existing guidelines to aid clinicians. Challenges remain in defining this disease and, most importantly appropriate empiric antimicrobial treatment is the main determinant of outcome. We highlight that the selection of initial antibiotics is critical, as VAP can by caused by a broad array of drug resistant organisms (DROs), the appropriate duration of treatment for VAP is an evolving concept, but may, in part, be guided by biomarkers, and provide focus on diagnostic challenges, initial therapies and treatment strategies for VAP. Both traditional and novel antimicrobials are presented, including developments in the modes of delivery. Expert commentary: The clinical approach to VAP continues to evolve. Recent evidence regarding the changes in microbiology, diagnostics approaches, and treatment strategies for VAP are important for clinicians to remain informed of to provide optimal patient care.


Assuntos
Antibacterianos/uso terapêutico , Cuidados Críticos/métodos , Pneumopatias Fúngicas/tratamento farmacológico , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Associada à Ventilação Mecânica/diagnóstico , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/mortalidade , Infecções por Bactérias Gram-Positivas/diagnóstico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Pneumopatias Fúngicas/diagnóstico , Pneumopatias Fúngicas/microbiologia , Pneumopatias Fúngicas/mortalidade , Pneumonia Bacteriana/diagnóstico , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/mortalidade , Pneumonia Associada à Ventilação Mecânica/microbiologia , Pneumonia Associada à Ventilação Mecânica/mortalidade , Guias de Prática Clínica como Assunto
10.
Clin Microbiol Infect ; 22(9): 782-787, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26806254

RESUMO

Invasive fungal infections (IFI) remain life-threatening complications in haematological patients. The aim of the study was to present the experience of a single centre in the surgical treatment of pulmonary IFI. Between 1992 and 2014, 50 haematological patients with IFI underwent pulmonary resection. In 27 cases it was an emergency procedure to avoid haemoptysis (if the lesion threatened pulmonary vessels). The remaining 23 patients underwent elective surgery before new chemotherapy or stem-cell transplantation. Among these patients (median age: 54 years; range: 5-70 years), 92% had acute leukaemia and 68% were on haematological first-line therapy (receiving induction or consolidation chemotherapies). Invasive pulmonary aspergillosis and pulmonary mucormycosis were diagnosed in 37 and 12 patients, respectively. One patient had IFI due to Trichoderma longibrachiatum. All of the patients received antifungal agents. In the month preceding IFI diagnosis, 94% of patients had been neutropenic. At the time of surgery, 30% of patients were still neutropenic and 54% required platelet transfusions. Lobectomy or segmentectomy were performed in 80% and 20% of cases, respectively. Mortality at 30 and 90 days post-surgery was 6% and 10%, respectively. After surgery, median overall survival was 21 months; median overall survival was similar between patients with emergency or elective surgery and between the types of IFI (invasive pulmonary aspergillosis or pulmonary mucormycosis). However, overall survival was far better in haematological first-line patients or in those achieving a haematological complete response than in other patients (p <0.001). In pulmonary IFI, lung resection could be an effective complement to medical treatment in selected haematological patients.


Assuntos
Doenças Hematológicas/complicações , Doenças Hematológicas/cirurgia , Infecções Fúngicas Invasivas/etiologia , Pneumopatias Fúngicas/etiologia , Procedimentos Cirúrgicos Pulmonares/efeitos adversos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Serviço Hospitalar de Emergência , Feminino , Seguimentos , Doenças Hematológicas/terapia , Humanos , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/mortalidade , Pneumopatias Fúngicas/diagnóstico , Pneumopatias Fúngicas/mortalidade , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados da Assistência ao Paciente , Pneumonectomia/efeitos adversos , Pneumonectomia/métodos , Modelos de Riscos Proporcionais , Procedimentos Cirúrgicos Pulmonares/métodos , Análise de Sobrevida , Tomografia Computadorizada por Raios X , Adulto Jovem
11.
J Immunol ; 194(12): 5999-6010, 2015 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-25972480

RESUMO

Numerous virulence factors expressed by Cryptococcus neoformans modulate host defenses by promoting nonprotective Th2-biased adaptive immune responses. Prior studies demonstrate that the heat shock protein 70 homolog, Ssa1, significantly contributes to serotype D C. neoformans virulence through the induction of laccase, a Th2-skewing and CNS tropic factor. In the present study, we sought to determine whether Ssa1 modulates host defenses in mice infected with a highly virulent serotype A strain of C. neoformans (H99). To investigate this, we assessed pulmonary fungal growth, CNS dissemination, and survival in mice infected with either H99, an SSA1-deleted H99 strain (Δssa1), and a complement strain with restored SSA1 expression (Δssa1::SSA1). Mice infected with the Δssa1 strain displayed substantial reductions in lung fungal burden during the innate phase (days 3 and 7) of the host response, whereas less pronounced reductions were observed during the adaptive phase (day 14) and mouse survival increased only by 5 d. Surprisingly, laccase activity assays revealed that Δssa1 was not laccase deficient, demonstrating that H99 does not require Ssa1 for laccase expression, which explains the CNS tropism we still observed in the Ssa1-deficient strain. Lastly, our immunophenotyping studies showed that Ssa1 directly promotes early M2 skewing of lung mononuclear phagocytes during the innate phase, but not the adaptive phase, of the immune response. We conclude that Ssa1's virulence mechanism in H99 is distinct and laccase-independent. Ssa1 directly interferes with early macrophage polarization, limiting innate control of C. neoformans, but ultimately has no effect on cryptococcal control by adaptive immunity.


Assuntos
Criptococose/imunologia , Criptococose/metabolismo , Cryptococcus neoformans/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Pneumopatias Fúngicas/imunologia , Pneumopatias Fúngicas/microbiologia , Macrófagos/imunologia , Imunidade Adaptativa , Animais , Encéfalo/metabolismo , Encéfalo/microbiologia , Encéfalo/patologia , Criptococose/mortalidade , Criptococose/patologia , Cryptococcus neoformans/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Regulação Fúngica da Expressão Gênica , Proteínas de Choque Térmico HSP70/genética , Imunidade Inata , Lacase/genética , Lacase/metabolismo , Leucócitos/imunologia , Leucócitos/patologia , Pneumopatias Fúngicas/mortalidade , Pneumopatias Fúngicas/patologia , Ativação de Macrófagos/imunologia , Camundongos , Mutação
12.
J Immunol ; 194(9): 4507-17, 2015 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-25825440

RESUMO

Pathogens are sensed by innate immune receptors that initiate an efficient adaptive immune response upon activation. The elements of the innate immune recognition process for Paracoccidioides brasiliensis include TLR-2, TLR-4, and dectin-1. However, there are additional receptors necessary for the host immune responses to P. brasiliensis. The nucleotide-binding oligomerization domain-like receptor (NLRs), which activate inflammasomes, are candidate receptors that deserve renewed investigation. After pathogen infection, the NLRs form large signaling platforms called inflammasomes, which lead to caspase-1 activation and maturation of proinflammatory cytokines (IL-18 and IL-1ß). In this study, we showed that NLR family pyrin domain-containing 3 (Nlrp3) is required to induce caspase-1 activation and further secretion of IL-1ß and IL-18 by P. brasiliensis-infected macrophages. Additionally, potassium efflux and lysosomal acidification induced by the fungus were important steps in the caspase-1 activation mechanism. Notably, Nlrp3 and caspase-1 knockout mice were more susceptible to infection than were the wild-type animals, suggesting that the Nlrp3-dependent inflammasomes contribute to host protection against P. brasiliensis. This protective effect occurred owing to the inflammatory response mediated by IL-18, as shown by an augmented fungus burden in IL-18 knockout mice. Taken together, our results show that the Nlrp3 inflammasome is essential for resistance against P. brasiliensis because it orchestrates robust caspase-1 activation and triggers an IL-18-dependent proinflammatory response.


Assuntos
Proteínas de Transporte/metabolismo , Imunidade Inata , Inflamassomos/metabolismo , Interleucina-18/metabolismo , Pneumopatias Fúngicas/imunologia , Pneumopatias Fúngicas/metabolismo , Animais , Caspase 1/metabolismo , Modelos Animais de Doenças , Resistência à Doença/genética , Resistência à Doença/imunologia , Granuloma/genética , Granuloma/imunologia , Granuloma/metabolismo , Inflamassomos/genética , Interleucina-18/genética , Interleucina-1beta/biossíntese , Pneumopatias Fúngicas/mortalidade , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/microbiologia , Masculino , Camundongos , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR , Paracoccidioides/imunologia
13.
Exp Clin Transplant ; 13 Suppl 1: 331-4, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25894185

RESUMO

OBJECTIVES: Pulmonary fungal infections remain the most important cause of morbidity and mortality in liver transplant recipients. Fast and accurate causative diagnoses are essential for a good outcome. Bronchoscopy with bronchoalveolar lavage frequently is performed to diagnose pulmonary infections in immunocompromised patients. The aim of this study was to evaluate the diagnostic use of bronchoalveolar lavage in liver transplant recipients with pulmonary infections. MATERIALS AND METHODS: We retrospectively analyzed the data of 408 patients who underwent liver transplant from January 1990 to December 2012. Patients who underwent bronchoalveolar lavage after transplant were included in this study. RESULTS: There were 18 of 408 liver transplant recipients (4.41%) who underwent bronchoalveolar lavage after transplant. The mean age was 49.5 ± 18 years. In 5 patients (27.8%), fungal microorganisms were observed in the cytology of bronchoalveolar lavage specimens, including Aspergillus fumigatus in 3 patients and Candida albicans in 2 patients. Death occurred in 4 of 5 patients (80%) with fungal infections. No association was observed between the presence of fungal infection and clinical and radiographic findings of the patients. CONCLUSIONS: Bronchoscopy with bronchoalveolar lavage is a useful, noninvasive diagnostic tool for the rapid diagnosis of infections in solid-organ transplant recipients.


Assuntos
Lavagem Broncoalveolar , Transplante de Fígado/efeitos adversos , Pneumopatias Fúngicas/diagnóstico , Pulmão/microbiologia , Infecções Oportunistas/diagnóstico , Adolescente , Adulto , Idoso , Líquido da Lavagem Broncoalveolar/microbiologia , Broncoscopia , Candidíase/diagnóstico , Candidíase/imunologia , Candidíase/microbiologia , Criança , Feminino , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Transplante de Fígado/mortalidade , Pulmão/imunologia , Pneumopatias Fúngicas/imunologia , Pneumopatias Fúngicas/microbiologia , Pneumopatias Fúngicas/mortalidade , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/imunologia , Infecções Oportunistas/microbiologia , Infecções Oportunistas/mortalidade , Valor Preditivo dos Testes , Aspergilose Pulmonar/diagnóstico , Aspergilose Pulmonar/imunologia , Aspergilose Pulmonar/microbiologia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
14.
Clin Infect Dis ; 60(9): 1368-76, 2015 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-25632012

RESUMO

BACKGROUND: Cryptococcus gattii (Cg) infection emerged in British Columbia in 1999. A longitudinal, clinical description of patients has not been reported. METHODS: Medical records were reviewed for Cg patients identified through surveillance (1999-2007). Risk factors for Cg mortality were explored using multivariate Cox regression; longitudinal patterns in serum cryptococcal antigen (SCrAg) titers and the probability of chest cryptococcomas over time were estimated using cubic B-splines in mixed-effects regression models. RESULTS: Among 152 patients, 111 (73.0%) were culture confirmed. Isolated lung infection was present in 105 (69.1%) patients; 47 (30.9%) had central nervous system infection, with or without lung involvement. Malignancy was the provisional diagnosis in 64 (42.1%) patients. Underlying diseases were present in 91 (59.9%) patients; 23 (15.1%) were immunocompromised, and 23 (15.1%) had asymptomatic disease. There were only 2 (1.8%) culture positive relapses, both within 12 months of follow-up. The estimated median time to resolution of lung cryptococcomas and decline in SCrAg titer to <1:8 was 2.8 and 2.9 years, respectively. Cg-related and all-cause mortality among culture-confirmed cases at 12 months' follow-up was 23.3% and 27.2%, respectively. Cg-related mortality was associated with age >50 years (hazard ratio [HR], 15.6; 95% confidence interval [CI], 1.9-130.5) and immunocompromise (HR, 5.8; CI, 1.5-21.6). All Cg-related mortality occurred among culture-positive cases within 1 year of diagnosis. CONCLUSIONS: Cryptococcomas and serum antigenemia were slow to resolve. However, late onset of failed therapy or relapse was uncommon, suggesting that delayed resolution of these findings does not require prolongation of treatment beyond that recommended by guidelines.


Assuntos
Criptococose/epidemiologia , Cryptococcus gattii , Pulmão/parasitologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Fungos/sangue , Colúmbia Britânica/epidemiologia , Criança , Pré-Escolar , Criptococose/diagnóstico , Criptococose/tratamento farmacológico , Criptococose/microbiologia , Criptococose/mortalidade , Cryptococcus gattii/isolamento & purificação , Cryptococcus gattii/patogenicidade , Feminino , Humanos , Hospedeiro Imunocomprometido , Estudos Longitudinais , Pulmão/diagnóstico por imagem , Pneumopatias Fúngicas/tratamento farmacológico , Pneumopatias Fúngicas/epidemiologia , Pneumopatias Fúngicas/microbiologia , Pneumopatias Fúngicas/mortalidade , Masculino , Pessoa de Meia-Idade , Radiografia , Recidiva , Análise de Regressão , Fatores de Risco , Fatores de Tempo , Adulto Jovem
15.
Pathologe ; 35(6): 606-11, 2014 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-25319227

RESUMO

Infectious pulmonary diseases and pneumonias are important causes of death within the group of infectious diseases in Germany. Most cases are triggered by bacteria. The morphology of the inflammation is often determined by the agent involved but several histopathological types of reaction are possible. Histology alone is only rarely able to identify the causal agent; therefore additional microbiological diagnostics are necessary in most cases. Clinically cases are classified as community acquired and nosocomial pneumonia, pneumonia under immunosuppression and mycobacterial infections. Histologically, alveolar and interstitial as well as lobar and focal pneumonia can be differentiated.


Assuntos
Pneumopatias Fúngicas/patologia , Pneumopatias Parasitárias/patologia , Pneumonia Bacteriana/patologia , Pneumonia Viral/patologia , Fatores Etários , Idoso , Causas de Morte , Estudos Transversais , Alemanha , Humanos , Pulmão/patologia , Pneumopatias Fúngicas/classificação , Pneumopatias Fúngicas/mortalidade , Pneumopatias Parasitárias/classificação , Pneumopatias Parasitárias/mortalidade , Técnicas Microbiológicas , Infecções Oportunistas/classificação , Infecções Oportunistas/mortalidade , Infecções Oportunistas/patologia , Pneumonia Bacteriana/classificação , Pneumonia Bacteriana/mortalidade , Pneumonia Viral/classificação , Pneumonia Viral/mortalidade , Tuberculose Pulmonar/classificação , Tuberculose Pulmonar/mortalidade , Tuberculose Pulmonar/patologia
16.
Exp Clin Transplant ; 12 Suppl 1: 110-6, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24635806

RESUMO

OBJECTIVES: We sought to assess the incidence of invasive fungal infections and identify the risk factors and outcome of invasive fungal infections in liver transplant recipient. MATERIALS AND METHODS: A retrospective analysis was made of 408 patients who received a liver transplant between January 1990 to December 2012 at Baskent University in Ankara, Turkey. Only 305 of 408 patients were included. Demographic and clinical findings were reviewed, and these findings were compared between patients with or without invasive fungal infections. RESULTS: Ten of 408 liver transplant patients (2.5%) developed invasive fungal infections. Aspergillus was the most common cause of invasive fungal infections (n=8), followed by Candida (n=1), and Cryptococcus neoformans (n=1). Pulmonary involvement was dominant in all patients (n=10), and only 1 patient had disseminated fungal infection (cryptococcosis). The mean time from transplant to invasive fungal infection diagnosis was 32 ± 19.2 days. Most patients with invasive fungal infection (9/10) died. Mean survival time between diagnosis of fungal infection and death was 24.2 ± 27.3 days in all 10 patients. Fungal infections occurred significantly more frequently in patients with older transplant age, diabetes mellitus, cytomegalovirus infection, renal insufficiency. In addition, other risk factors included long stays in the surgical intensive care unit, the overall length of stay in hospital, and having preoperative high creatinine level. CONCLUSIONS: Invasive fungal infections were associated with increased morbidity and mortality among liver transplant recipients, with Aspergillus spp. being the most common pathogen in our series. Because of its high mortality rate, it is important to follow up transplant patients for the development of invasive fungal infections.


Assuntos
Infecção Hospitalar/epidemiologia , Transplante de Fígado/efeitos adversos , Pneumopatias Fúngicas/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , Comorbidade , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/microbiologia , Infecção Hospitalar/mortalidade , Feminino , Mortalidade Hospitalar , Hospitais Universitários , Humanos , Incidência , Lactente , Aspergilose Pulmonar Invasiva/epidemiologia , Aspergilose Pulmonar Invasiva/microbiologia , Transplante de Fígado/mortalidade , Pneumopatias Fúngicas/diagnóstico , Pneumopatias Fúngicas/microbiologia , Pneumopatias Fúngicas/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Turquia/epidemiologia , Adulto Jovem
17.
Mycoses ; 57(1): 49-55, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23905713

RESUMO

Pulmonary mucormycosis (PM) is a life-threatening opportunistic mycosis with a variable clinical evolution and few prognostic markers for outcome assessment. Several clinical risk factors for poor outcome present at the diagnosis of PM were analyzed in 75 consecutive hematology patients from 2000-2012. Significant variables (P < 0.1) were entered into a multivariate Cox-proportional hazard regression model adjusting for baseline APACHE II to identify independent risk factors for mortality within 28 days. Twenty-eight of 75 patients died within 4-week follow up. A lymphocyte count < 100/mm³ at the time of diagnosis (adjusted hazard ratio 4.0, 1.7-9.4, P = 0.01) and high level of lactate dehydrogenase (AHR 3.7, 1.3-10.2, P = 0.015) were independent predictors along with APACHE II score for 28-day mortality. A weighted risk score based on these 3 baseline variables accurately identified non-surviving patients at 28 days (area under the receiver-operator curve of 0.87, 0.77-0.93, P < 0.001). A risk score > 22 was associated with 8-fold high rates of mortality (P < 0.0001) within 28 days of diagnosis and median survival of 7 days versus ≥28 days in patients with risk scores ≤22. We found that APACHE II score, severe lymphocytopenia and high LDH levels at the time of PM diagnosis were independent markers for rapid disease progression and death.


Assuntos
Neoplasias Hematológicas/mortalidade , Pneumopatias Fúngicas/mortalidade , Mucormicose/mortalidade , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/epidemiologia , Neoplasias Hematológicas/microbiologia , Humanos , Pneumopatias Fúngicas/complicações , Pneumopatias Fúngicas/epidemiologia , Pneumopatias Fúngicas/microbiologia , Masculino , Pessoa de Meia-Idade , Mucormicose/complicações , Mucormicose/epidemiologia , Mucormicose/microbiologia , Prognóstico , Fatores de Risco , Adulto Jovem
18.
Emerg Infect Dis ; 19(10): 1620-6, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24050410

RESUMO

Clonal VGII subtypes (outbreak strains) of Cryptococcus gattii have caused an outbreak in the US Pacific Northwest since 2004. Outbreak-associated infections occur equally in male and female patients (median age 56 years) and usually cause pulmonary disease in persons with underlying medical conditions. Since 2009, a total of 25 C. gattii infections, 23 (92%) caused by non-outbreak strain C. gattii, have been reported from 8 non-Pacific Northwest states. Sixteen (64%) patients were previously healthy, and 21 (84%) were male; median age was 43 years (range 15-83 years). Ten patients who provided information reported no past-year travel to areas where C. gattii is known to be endemic. Nineteen (76%) patients had central nervous system infections; 6 (24%) died. C. gattii infection in persons without exposure to known disease-endemic areas suggests possible endemicity in the United States outside the outbreak-affected region; these infections appear to differ in clinical and demographic characteristics from outbreak-associated C. gattii. Clinicians outside the outbreak-affected areas should be aware of locally acquired C. gattii infection and its varied signs and symptoms.


Assuntos
Criptococose/mortalidade , Cryptococcus gattii/imunologia , Pneumopatias Fúngicas/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criptococose/imunologia , Criptococose/microbiologia , Cryptococcus gattii/genética , Surtos de Doenças , Feminino , Genótipo , Humanos , Pneumopatias Fúngicas/imunologia , Pneumopatias Fúngicas/microbiologia , Masculino , Pessoa de Meia-Idade , Filogenia , Estados Unidos/epidemiologia , Adulto Jovem
19.
Emerg Infect Dis ; 19(10): 1590-7, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24050438

RESUMO

In the past decade, state-specific increases in the number of reported cases of coccidioidomycosis have been observed in areas of California and Arizona where the disease is endemic. Although most coccidioidomycosis is asymptomatic or mild, infection can lead to severe pulmonary or disseminated disease requiring hospitalization and costly disease management. To determine the epidemiology of cases and toll of coccidioidomycosis-associated hospitalizations in California, we reviewed hospital discharge data for 2000-2011. During this period, there were 25,217 coccidioidomycosis-associated hospitalizations for 15,747 patients and >$2 billion US in total hospital charges. Annual initial hospitalization rates increased from 2.3 initial hospitalizations/100,000 population in 2000 to 5.0 initial hospitalizations/100,000 population in 2011. During this period, initial hospitalization rates were higher for men than women, African Americans and Hispanics than Whites, and older persons than younger persons. In California, the increasing health- and cost-related effects of coccidioidomycosis-associated hospitalizations are a major public health challenge.


Assuntos
Coccidioidomicose/mortalidade , Hospitalização/estatística & dados numéricos , Pneumopatias Fúngicas/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , California/epidemiologia , Criança , Pré-Escolar , Coccidioidomicose/epidemiologia , Coccidioidomicose/terapia , Feminino , Preços Hospitalares , Hospitalização/economia , Humanos , Incidência , Lactente , Tempo de Internação/economia , Tempo de Internação/estatística & dados numéricos , Pneumopatias Fúngicas/terapia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
20.
PLoS One ; 6(2): e17204, 2011 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-21359196

RESUMO

The current studies evaluated the role of interleukin (IL)-17A in the induction of protective immunity against pulmonary cryptococcosis in mice. Protection against pulmonary infection with C. neoformans strain H99γ was associated with increased IL-17A production. Signaling through the IFN-γ receptor (R) was required for increased IL-17A production, however, a Th17-type cytokine profile was not observed. Neutrophils were found to be the predominant leukocytic source of IL-17A, rather than T cells, suggesting that the IL-17A produced was not part of a T cell-mediated Th17-type immune response. Depletion of IL-17A in mice during pulmonary infection with C. neoformans strain H99γ resulted in an initial increase in pulmonary fungal burden, but had no effect on cryptococcal burden at later time points. Also, depletion of IL-17A did not affect the local production of other cytokines. IL-17RA⁻/⁻ mice infected with C. neoformans strain H99γ survived the primary infection as well as a secondary challenge with wild-type cryptococci. However, dissemination of the wild-type strain to the brain was noted in the surviving IL-17RA⁻/⁻ mice. Altogether, our results suggested that IL-17A may be important for optimal protective immune responsiveness during pulmonary C. neoformans infection, but protective Th1-type immune responses are sufficient for protection against cryptococcal infection.


Assuntos
Criptococose/imunologia , Cryptococcus neoformans/imunologia , Imunidade Celular/genética , Interleucina-17/fisiologia , Pneumopatias Fúngicas/imunologia , Animais , Quimiotaxia de Leucócito/genética , Criptococose/genética , Criptococose/mortalidade , Cryptococcus neoformans/metabolismo , Cryptococcus neoformans/fisiologia , Citoproteção/genética , Citoproteção/imunologia , Feminino , Interleucina-17/genética , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Pneumopatias Fúngicas/genética , Pneumopatias Fúngicas/metabolismo , Pneumopatias Fúngicas/mortalidade , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Células Th1/imunologia , Células Th1/metabolismo , Células Th1/fisiologia , Células Th17/imunologia , Células Th17/metabolismo , Células Th17/fisiologia
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