Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 51
Filtrar
1.
J Antimicrob Chemother ; 76(3): 635-638, 2021 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-33374010

RESUMO

BACKGROUND: The performance of the galactomannan enzyme immunoassay (GM-EIA) is impaired in patients receiving mould-active antifungal therapy. The impact of mould-active antifungal therapy on Aspergillus PCR testing needs to be determined. OBJECTIVES: To determine the influence of anti-mould prophylaxis (AMP) on the performance of PCR blood testing to aid the diagnosis of proven/probable invasive aspergillosis (IA). METHODS: As part of the systematic review and meta-analysis of 22 cohort studies investigating Aspergillus PCR blood testing in 2912 patients at risk of IA, subgroup analysis was performed to determine the impact of AMP on the accuracy of Aspergillus PCR. The incidence of IA was calculated in patients receiving and not receiving AMP. The impact of two different positivity thresholds (requiring either a single PCR positive test result or ≥2 consecutive PCR positive test results) on accuracy was evaluated. Meta-analytical pooling of sensitivity and specificity was performed by logistic mixed-model regression. RESULTS: In total, 1661 (57%) patients received prophylaxis. The incidence of IA was 14.2%, significantly lower in the prophylaxis group (11%-12%) compared with the non-prophylaxis group (18%-19%) (P < 0.001). The use of AMP did not affect sensitivity, but significantly decreased specificity [single PCR positive result threshold: 26% reduction (P = 0.005); ≥2 consecutive PCR positive results threshold: 12% reduction (P = 0.019)]. CONCLUSIONS: Contrary to its influence on GM-EIA, AMP significantly decreases Aspergillus PCR specificity, without affecting sensitivity, possibly as a consequence of AMP limiting the clinical progression of IA and/or leading to false-negative GM-EIA results, preventing the classification of probable IA using the EORTC/MSGERC definitions.


Assuntos
Aspergilose , Infecções Fúngicas Invasivas , Aspergilose/diagnóstico , Aspergilose/prevenção & controle , Aspergillus/genética , Humanos , Mananas , Metanálise como Assunto , Reação em Cadeia da Polimerase , Sensibilidade e Especificidade
2.
Ann Hematol ; 98(5): 1051-1069, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30796468

RESUMO

Sepsis and septic shock are major causes of mortality during chemotherapy-induced neutropenia for malignancies requiring urgent treatment. Thus, awareness of the presenting characteristics and prompt management is most important. Improved management of sepsis during neutropenia may reduce the mortality of cancer therapies. However, optimal management may differ between neutropenic and non-neutropenic patients. The aim of the current guideline is to give evidence-based recommendations for hematologists, oncologists, and intensive care physicians on how to manage adult patients with neutropenia and sepsis.


Assuntos
Neutropenia Febril Induzida por Quimioterapia/terapia , Neoplasias/terapia , Sepse , Adulto , Neutropenia Febril Induzida por Quimioterapia/etiologia , Cuidados Críticos , Feminino , Alemanha , Hematologia , Humanos , Masculino , Oncologia , Guias de Prática Clínica como Assunto , Sepse/etiologia , Sepse/terapia , Sociedades Médicas
3.
J Crit Care ; 47: 198-203, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30015290

RESUMO

Invasive pulmonary aspergillosis (IPA) is an emerging and life-threatening infectious disease in patients admitted to the intensive care unit (ICU). Most diagnostic studies are conducted in hematological patients and results cannot readily be transferred to ICU patients lacking classical host factors. In a multicenter, prospective clinical trial including 44 ICU patients, hematological (n = 14) and non-hematological patients (n = 30), concurrent serum and bronchoalveolar lavage (BAL) samples were analyzed by conventional culture, galactomannan (GM), 1-3-beta-D-glucan (BDG) as well as an Aspergillus specific nested polymerase chain reaction (PCR). Nine patients (20%) had putative IPA according to AspICU classification. GM and PCR showed superior performance in BAL with sensitivity/specificity of 56%/94% and 44%/94% compared to 33%/97% and 11%/94% in serum. Despite better sensitivity of 89%, BDG showed poor specificity of only 31% (BAL) and 26% (serum). Combination of GM and PCR (BAL) with BDG (serum) resulted in 100% sensitivity, but also reduced specificity to 23%. Whereas mean GM levels were significantly higher in hematological patients BDG and PCR did not differ between hematological and non-hematological patients. Under present clinical conditions test combinations integrating both BAL and blood samples are advantageous. BDG might best serve as possible indicator for ruling out IPA. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01695499. First posted: September 28, 2012, last update posted: May 8, 2017.


Assuntos
Aspergillus/isolamento & purificação , Líquido da Lavagem Broncoalveolar/microbiologia , Estado Terminal , Aspergilose Pulmonar Invasiva/microbiologia , Reação em Cadeia da Polimerase , Adulto , Idoso , Idoso de 80 Anos ou mais , Testes Diagnósticos de Rotina , Galactose/análogos & derivados , Humanos , Masculino , Mananas/análise , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Adulto Jovem , beta-Glucanas/análise
4.
Ann Oncol ; 29(6): 1354-1365, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29688266

RESUMO

Infectious complications are a significant cause of morbidity and mortality in patients with malignancies specifically when receiving anticancer treatments. Prevention of infection through vaccines is an important aspect of clinical care of cancer patients. Immunocompromising effects of the underlying disease as well as of antineoplastic therapies need to be considered when devising vaccination strategies. This guideline provides clinical recommendations on vaccine use in cancer patients including autologous stem cell transplant recipients, while allogeneic stem cell transplantation is subject of a separate guideline. The document was prepared by the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) by reviewing currently available data and applying evidence-based medicine criteria.


Assuntos
Anti-Infecciosos/uso terapêutico , Doenças Transmissíveis/tratamento farmacológico , Neoplasias Hematológicas/terapia , Neoplasias/terapia , Guias de Prática Clínica como Assunto/normas , Transplante de Células-Tronco/efeitos adversos , Vacinação/normas , Doenças Transmissíveis/etiologia , Humanos , Prognóstico
6.
Clin Microbiol Infect ; 24 Suppl 1: e1-e38, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29544767

RESUMO

The European Society for Clinical Microbiology and Infectious Diseases, the European Confederation of Medical Mycology and the European Respiratory Society Joint Clinical Guidelines focus on diagnosis and management of aspergillosis. Of the numerous recommendations, a few are summarized here. Chest computed tomography as well as bronchoscopy with bronchoalveolar lavage (BAL) in patients with suspicion of pulmonary invasive aspergillosis (IA) are strongly recommended. For diagnosis, direct microscopy, preferably using optical brighteners, histopathology and culture are strongly recommended. Serum and BAL galactomannan measures are recommended as markers for the diagnosis of IA. PCR should be considered in conjunction with other diagnostic tests. Pathogen identification to species complex level is strongly recommended for all clinically relevant Aspergillus isolates; antifungal susceptibility testing should be performed in patients with invasive disease in regions with resistance found in contemporary surveillance programmes. Isavuconazole and voriconazole are the preferred agents for first-line treatment of pulmonary IA, whereas liposomal amphotericin B is moderately supported. Combinations of antifungals as primary treatment options are not recommended. Therapeutic drug monitoring is strongly recommended for patients receiving posaconazole suspension or any form of voriconazole for IA treatment, and in refractory disease, where a personalized approach considering reversal of predisposing factors, switching drug class and surgical intervention is also strongly recommended. Primary prophylaxis with posaconazole is strongly recommended in patients with acute myelogenous leukaemia or myelodysplastic syndrome receiving induction chemotherapy. Secondary prophylaxis is strongly recommended in high-risk patients. We strongly recommend treatment duration based on clinical improvement, degree of immunosuppression and response on imaging.


Assuntos
Antifúngicos/uso terapêutico , Aspergilose/diagnóstico , Aspergilose/tratamento farmacológico , Aspergillus/isolamento & purificação , Gerenciamento Clínico , Anticorpos Antifúngicos/sangue , Antifúngicos/farmacologia , Aspergilose/complicações , Aspergilose/imunologia , Aspergillus/efeitos dos fármacos , Aspergillus/imunologia , Biópsia/métodos , Lavagem Broncoalveolar , Diagnóstico Precoce , Flucitosina/farmacologia , Flucitosina/uso terapêutico , Galactose/análogos & derivados , Humanos , Hospedeiro Imunocomprometido , Testes Imunológicos , Aspergilose Pulmonar Invasiva/diagnóstico , Itraconazol/farmacologia , Itraconazol/uso terapêutico , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/terapia , Imageamento por Ressonância Magnética , Mananas/análise , Testes de Sensibilidade Microbiana , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/terapia , Nitrilas/farmacologia , Nitrilas/uso terapêutico , Piridinas/farmacologia , Piridinas/uso terapêutico , Tomografia Computadorizada por Raios X , Triazóis/farmacologia , Triazóis/uso terapêutico , Voriconazol/farmacologia , Voriconazol/uso terapêutico
7.
Ann Hematol ; 97(1): 31-49, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29177551

RESUMO

Cancer patients frequently suffer from gastrointestinal complications. In this manuscript, we update our 2013 guideline on the diagnosis and management of gastrointestinal complications in adult cancer patients by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO). An expert group was put together by the AGIHO to update the existing guideline. For each sub-topic, a literature search was performed in PubMed, Medline, and Cochrane databases, and strengths of recommendation and the quality of the published evidence for major therapeutic strategies were categorized using the 2015 European Society for Clinical Microbiology and Infectious Diseases (ESCMID) criteria. Final recommendations were approved by the AGIHO plenary conference. Recommendations were made with respect to non-infectious and infectious gastrointestinal complications. Strengths of recommendation and levels of evidence are presented. A multidisciplinary approach to the diagnosis and management of gastrointestinal complications in cancer patients is mandatory. Evidence-based recommendations are provided in this updated guideline.


Assuntos
Gastroenteropatias/diagnóstico , Gastroenteropatias/etiologia , Gastroenteropatias/terapia , Neoplasias/complicações , Adulto , Doenças Transmissíveis/terapia , Alemanha , Hematologia/organização & administração , Hematologia/normas , Humanos , Oncologia/organização & administração , Oncologia/normas , Neoplasias/diagnóstico , Neoplasias/terapia , Guias de Prática Clínica como Assunto , Sociedades Médicas/organização & administração , Sociedades Médicas/normas
8.
Ann Hematol ; 96(11): 1775-1792, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28856437

RESUMO

Fever may be the only clinical symptom at the onset of infection in neutropenic cancer patients undergoing myelosuppressive chemotherapy. A prompt and evidence-based diagnostic and therapeutic approach is mandatory. A systematic search of current literature was conducted, including only full papers and excluding allogeneic hematopoietic stem cell transplant recipients. Recommendations for diagnosis and therapy were developed by an expert panel and approved after plenary discussion by the AGIHO. Randomized clinical trials were mainly available for therapeutic decisions, and new diagnostic procedures have been introduced into clinical practice in the past decade. Stratification into a high-risk versus low-risk patient population is recommended. In high-risk patients, initial empirical antimicrobial therapy should be active against pathogens most commonly involved in microbiologically documented and most threatening infections, including Pseudomonas aeruginosa, but excluding coagulase-negative staphylococci. In patients whose expected duration of neutropenia is more than 7 days and who do not respond to first-line antibacterial treatment, specifically in the absence of mold-active antifungal prophylaxis, further therapy should be directed also against fungi, in particular Aspergillus species. With regard to antimicrobial stewardship, treatment duration after defervescence in persistently neutropenic patients must be critically reconsidered and the choice of anti-infective agents adjusted to local epidemiology. This guideline updates recommendations for diagnosis and empirical therapy of fever of unknown origin in adult neutropenic cancer patients in light of the challenges of antimicrobial stewardship.


Assuntos
Doenças Transmissíveis/diagnóstico , Febre de Causa Desconhecida/diagnóstico , Hematologia/normas , Oncologia/normas , Neutropenia/diagnóstico , Guias de Prática Clínica como Assunto/normas , Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis/terapia , Febre de Causa Desconhecida/epidemiologia , Febre de Causa Desconhecida/terapia , Alemanha/epidemiologia , Hematologia/métodos , Humanos , Oncologia/métodos , Neutropenia/epidemiologia , Neutropenia/terapia , Sociedades Médicas/normas
9.
Sci Rep ; 7(1): 4483, 2017 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-28667276

RESUMO

Invasive pulmonary aspergillosis (IPA) is one of the major complications in immunocompromised patients. The mainstay of diagnostic imaging is non-enhanced chest-computed-tomography (CT), for which various non-specific signs for IPA have been described. However, contrast-enhanced CT pulmonary angiography (CTPA) has shown promising results, as the vessel occlusion sign (VOS) seems to be more sensitive and specific for IPA in hematologic patients. The aim of this study was to evaluate the diagnostic accuracy of CTPA in a larger cohort including non-hematologic immunocompromised patients. CTPA studies of 78 consecutive immunocompromised patients with proven/probable IPA were analyzed. 45 immunocompromised patients without IPA served as a control group. Diagnostic performance of CTPA-detected VOS and of radiological signs that do not require contrast-media were analyzed. Of 12 evaluable radiological signs, five were found to be significantly associated with IPA. The VOS showed the highest diagnostic performance with a sensitivity of 0.94, specificity of 0.71 and a diagnostic odds-ratio of 36.8. Regression analysis revealed the two strongest independent radiological predictors for IPA to be the VOS and the halo sign. The VOS is highly suggestive for IPA in immunocompromised patients in general. Thus, contrast-enhanced CTPA superior over non-contrast_enhanced chest-CT in patients with suspected IPA.


Assuntos
Angiografia por Tomografia Computadorizada , Hospedeiro Imunocomprometido , Aspergilose Pulmonar/diagnóstico , Intensificação de Imagem Radiográfica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifúngicos , Criança , Pré-Escolar , Angiografia por Tomografia Computadorizada/métodos , Angiografia por Tomografia Computadorizada/normas , Meios de Contraste , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neutropenia/etiologia , Neutropenia/patologia , Aspergilose Pulmonar/tratamento farmacológico , Aspergilose Pulmonar/etiologia , Aspergilose Pulmonar/microbiologia , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Adulto Jovem
10.
Clin Microbiol Infect ; 22(10): 862-868, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27393123

RESUMO

High mortality rates of invasive fungal disease (IFD), especially invasive aspergillosis (IA), in immunocompromised haematological patients and current diagnostic limitations require improvement of detection of fungal pathogens by defining the optimal use of biomarkers and clinical samples. Concurrent bronchoalveolar lavage (BAL) and peripheral blood samples of 99 haematological patients with suspected IFD were investigated within a multicentre prospective study. Diagnostic performance of a galactomannan (GM) enzyme immune assay (EIA), a 1,3-ß-D-glucan assay (BDG), an Aspergillus PCR, and a multifungal DNA-microarray (Chip) alone or in combination were calculated. IFD were classified as proven (n=3), probable (n=34), possible (n=33), and no IFD (n=29) according to EORTC/MSG criteria. GM, PCR, and Chip showed superior diagnostic performance in BAL than in blood, whereas specificity of BDG in BAL was poor (48% (14/29)). The combination of GM (BAL) with BDG (blood) showed sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and DOR (diagnostic odds ratio) of 92% (34/37), 93% (27/29), 94%, 90%, and 153.0, respectively. Combining GM (BAL) with PCR (BAL) showed convincing diagnostic potential for diagnosing IA with sensitivity, specificity, PPV, NPV, and DOR of 85% (17/20), 97% (28/29), 94%, 90%, and 158.7. Addition of the DNA-microarray resulted in further detection of two mucormycetes infections. In 1 out of 15 Aspergillus DNA-positive samples a triazole resistance-mediating Cyp51A mutation was found. Combination of biomarkers is superior to their sole use in diagnosing IFD, particularly IA. Integrating blood and BAL samples into a diagnostic algorithm is an advantageous approach.


Assuntos
Aspergilose/diagnóstico , Líquido da Lavagem Broncoalveolar/microbiologia , Infecções Fúngicas Invasivas/diagnóstico , Técnicas Microbiológicas/métodos , Técnicas de Diagnóstico Molecular/métodos , Aspergilose/sangue , Aspergillus/efeitos dos fármacos , Aspergillus/genética , Azóis/farmacologia , Galactose/análogos & derivados , Humanos , Infecções Fúngicas Invasivas/sangue , Mananas/análise , Reação em Cadeia da Polimerase Multiplex/métodos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Estudos Prospectivos , Sensibilidade e Especificidade , beta-Glucanas/análise
11.
Ann Oncol ; 27(7): 1207-25, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27052648

RESUMO

Infections of the central nervous system (CNS) are infrequently diagnosed in immunocompetent patients, but they do occur in a significant proportion of patients with hematological disorders. In particular, patients undergoing allogeneic hematopoietic stem-cell transplantation carry a high risk for CNS infections of up to 15%. Fungi and Toxoplasma gondii are the predominant causative agents. The diagnosis of CNS infections is based on neuroimaging, cerebrospinal fluid examination and biopsy of suspicious lesions in selected patients. However, identification of CNS infections in immunocompromised patients could represent a major challenge since metabolic disturbances, side-effects of antineoplastic or immunosuppressive drugs and CNS involvement of the underlying hematological disorder may mimic symptoms of a CNS infection. The prognosis of CNS infections is generally poor in these patients, albeit the introduction of novel substances (e.g. voriconazole) has improved the outcome in distinct patient subgroups. This guideline has been developed by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO) with the contribution of a panel of 14 experts certified in internal medicine, hematology/oncology, infectious diseases, intensive care, neurology and neuroradiology. Grades of recommendation and levels of evidence were categorized by using novel criteria, as recently published by the European Society of Clinical Microbiology and Infectious Diseases.


Assuntos
Sistema Nervoso Central/fisiopatologia , Doenças Transmissíveis/fisiopatologia , Doenças Hematológicas/microbiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Sistema Nervoso Central/microbiologia , Doenças Transmissíveis/diagnóstico , Doenças Transmissíveis/tratamento farmacológico , Doenças Transmissíveis/microbiologia , Alemanha/epidemiologia , Guias como Assunto , Doenças Hematológicas/tratamento farmacológico , Doenças Hematológicas/epidemiologia , Doenças Hematológicas/fisiopatologia , Hematologia , Humanos , Oncologia , Toxoplasma/patogenicidade , Voriconazol/uso terapêutico
12.
Mycoses ; 58(12): 735-45, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26497302

RESUMO

The increasing incidence of invasive fungal diseases (IFD), most of all invasive aspergillosis (IA) in immunocompromised patients emphasises the need to improve the diagnostic tools for detection of fungal pathogens. We investigated the diagnostic performance of a multifungal DNA-microarray detecting 15 different fungi [Aspergillus, Candida, Fusarium, Mucor, Rhizopus, Scedosporium and Trichosporon species (spp.)] in addition to an Aspergillus specific polymerase chain reaction (PCR) assay. Biopsies, bronchoalveolar lavage and peripheral blood samples of 133 immunocompromised patients (pts) were investigated by a multifungal DNA-microarray as well as a nested Aspergillus specific PCR assay. Patients had proven (n = 18), probable (n = 29), possible (n = 48) and no IFD (n = 38) and were mostly under antifungal therapy at the time of sampling. The results were compared to culture, histopathology, imaging and serology, respectively. For the non-Aspergillus IFD the microarray analysis yielded in all samples a sensitivity of 64% and a specificity of 80%. Best results for the detection of all IFD were achieved by combining DNA-microarray and Aspergillus specific PCR in biopsy samples (sensitivity 79%; specificity 71%). The molecular assays in combination identify genomic DNA of fungal pathogens and may improve identification of causative pathogens of IFD and help overcoming the diagnostic uncertainty of culture and/or histopathology findings, even during antifungal therapy.


Assuntos
Aspergilose/diagnóstico , Aspergillus fumigatus/isolamento & purificação , Reação em Cadeia da Polimerase Multiplex/métodos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Adulto , Antifúngicos/uso terapêutico , Aspergilose/sangue , Aspergilose/diagnóstico por imagem , Aspergillus fumigatus/genética , Aspergillus fumigatus/imunologia , Sequência de Bases , Biópsia por Agulha , Lavagem Broncoalveolar , DNA Fúngico/isolamento & purificação , Feminino , Humanos , Hospedeiro Imunocomprometido , Masculino , Dados de Sequência Molecular , Radiografia , Sensibilidade e Especificidade
13.
J Antimicrob Chemother ; 70(5): 1522-6, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25630644

RESUMO

OBJECTIVES: Aspergillus fumigatus is the most common agent of invasive aspergillosis (IA). In recent years, resistance to triazoles, the mainstay of IA therapy, has emerged in different countries worldwide. IA caused by azole-resistant A. fumigatus (ARAF) shows an exceedingly high mortality. In this study, IA due to ARAF isolates in HSCT recipients in Germany was investigated. METHODS: The epidemiology of azole resistance in IA was analysed in two German haematology departments. Between 2012 and 2013, 762 patients received HSCT in Essen (n = 388) and Cologne (n = 374). Susceptibility testing of A. fumigatus isolates was performed by Etest, followed by EUCAST broth microdilution testing if elevated MICs were recorded. In all ARAF isolates the cyp51A gene was sequenced and the genotype was determined by microsatellite typing using nine short tandem repeats. RESULTS: In total, A. fumigatus was recovered from 27 HSCT recipients. Eight patients had azole-resistant IA after HSCT, and seven of the cases were fatal (88%). All except one patient received antifungal prophylaxis (in five cases triazoles). TR34/L98H was the most common mutation (n = 5), followed by TR46/Y121F/T289A (n = 2). In one resistant isolate no cyp51A mutation was detected. Genotyping revealed genetic diversity within the German ARAF isolates and no clustering with resistant isolates from the Netherlands, India and France. CONCLUSIONS: This report highlights the emergence of azole-resistant IA with TR34/L98H and TR46/Y121F/T289A mutations in HSCT patients in Germany and underscores the need for systematic antifungal susceptibility testing of A. fumigatus.


Assuntos
Antifúngicos/farmacologia , Aspergillus fumigatus/efeitos dos fármacos , Azóis/farmacologia , Farmacorresistência Fúngica , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Aspergilose Pulmonar Invasiva/epidemiologia , Adulto , Idoso , Substituição de Aminoácidos , Aspergillus fumigatus/classificação , Aspergillus fumigatus/genética , Aspergillus fumigatus/isolamento & purificação , Sistema Enzimático do Citocromo P-450/genética , Feminino , Proteínas Fúngicas/genética , Genótipo , Alemanha/epidemiologia , Humanos , Masculino , Testes de Sensibilidade Microbiana , Repetições de Microssatélites , Pessoa de Meia-Idade , Tipagem Molecular , Proteínas Mutantes/genética , Técnicas de Tipagem Micológica , Análise de Sequência de DNA
14.
Ann Oncol ; 26(1): 21-33, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24833776

RESUMO

Up to 25% of patients with profound neutropenia lasting for >10 days develop lung infiltrates, which frequently do not respond to broad-spectrum antibacterial therapy. While a causative pathogen remains undetected in the majority of cases, Aspergillus spp., Pneumocystis jirovecii, multi-resistant Gram-negative pathogens, mycobacteria or respiratory viruses may be involved. In at-risk patients who have received trimethoprim-sulfamethoxazole (TMP/SMX) prophylaxis, filamentous fungal pathogens appear to be predominant, yet commonly not proven at the time of treatment initiation. Pathogens isolated from blood cultures, bronchoalveolar lavage (BAL) or respiratory secretions are not always relevant for the etiology of pulmonary infiltrates and should therefore be interpreted critically. Laboratory tests for detecting Aspergillus galactomannan, ß-D-glucan or DNA from blood, BAL or tissue samples may facilitate the diagnosis; however, most polymerase chain reaction assays are not yet standardized and validated. Apart from infectious agents, pulmonary side-effects from cytotoxic drugs, radiotherapy or pulmonary involvement by the underlying malignancy should be included into differential diagnosis and eventually be clarified by invasive diagnostic procedures. Pre-emptive treatment with mold-active systemic antifungal agents improves clinical outcome, while other microorganisms are preferably treated only when microbiologically documented. High-dose TMP/SMX is first choice for treatment of Pneumocystis pneumonia, while cytomegalovirus pneumonia is treated primarily with ganciclovir or foscarnet in most patients. In a considerable number of patients, clinical outcome may be favorable despite respiratory failure, so that intensive care should be unrestrictedly provided in patients whose prognosis is not desperate due to other reasons.


Assuntos
Anti-Infecciosos/uso terapêutico , Líquido da Lavagem Broncoalveolar , Pneumopatias/diagnóstico , Pneumopatias/tratamento farmacológico , Líquido da Lavagem Broncoalveolar/microbiologia , Líquido da Lavagem Broncoalveolar/parasitologia , Líquido da Lavagem Broncoalveolar/virologia , Combinação de Medicamentos , Febre , Humanos , Pulmão/microbiologia , Pulmão/parasitologia , Pulmão/virologia , Pneumopatias/microbiologia , Neutropenia , Sulfadoxina/uso terapêutico , Supuração/microbiologia , Supuração/parasitologia , Supuração/virologia , Trimetoprima/uso terapêutico
16.
Mycoses ; 57(9): 537-43, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24655146

RESUMO

Invasive aspergillosis (IA) remains difficult to diagnose in immunocompromised patients, because diagnostic EORTC/MSG criteria are often not met. As biomarkers might elucidate the pathogen, we analysed the performance of an Aspergillus PCR assay in blood for diagnosis of IA in immunocompromised paediatric patients with suspected infections. Ninety-five haemato-oncological paediatric patients were included over a period of 3 years, the underlying diseases consisting of acute leukaemia, solid tumours, non-malignant immunocompromising disorders and haematopoietic stem cell transplantation recipients. We retrospectively analysed 253 consecutive episodes of suspected infections. Thirty-eight patients had possible IA, none of the patients fulfilled EORTC/MSG criteria of probable/proven IA. PCR positivity was observed in 97/967 analyses. Sensitivity, specificity, positive and negative predictive value of the PCR per episode were 34%, 78%, 31% and 81% using possible IA as endpoint. Taken together, an undirected blood screening by Aspergillus-specific PCR is of little diagnostic value in a heterogenous paediatric patient cohort. Harnessing PCR for diagnosis of IA should thus be focused on blood analyses of more homogenous high-risk patients and/or analyses of bronchoalveolar lavage, tissue or cerebrospinal fluid specimens.


Assuntos
Aspergillus/isolamento & purificação , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Aspergilose Pulmonar Invasiva/diagnóstico , Programas de Rastreamento/métodos , Técnicas de Diagnóstico Molecular/métodos , Neoplasias/complicações , Reação em Cadeia da Polimerase/métodos , Adolescente , Aspergillus/genética , Sangue/microbiologia , Criança , Pré-Escolar , DNA Fúngico/sangue , DNA Fúngico/química , DNA Fúngico/genética , Feminino , Humanos , Hospedeiro Imunocomprometido , Lactente , Aspergilose Pulmonar Invasiva/microbiologia , Masculino , Dados de Sequência Molecular , Sensibilidade e Especificidade , Análise de Sequência de DNA , Adulto Jovem
17.
J Clin Microbiol ; 52(6): 2039-45, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24671798

RESUMO

Galactomannan detection in bronchoalveolar lavage (BAL) fluid samples (GM test) is currently considered the gold standard test for diagnosing invasive pulmonary aspergillosis (IPA). The limitations, however, are the various turnaround times and availability of testing. We compared the performance of GM testing with that of conventional culture, an Aspergillus lateral-flow-device (LFD) test, a beta-d-glucan (BDG) test, and an Aspergillus PCR assay by using BAL fluid samples from immunocompromised patients. A total of 78 BAL fluid samples from 78 patients at risk for IPA (74 samples from Graz and 4 from Mannheim) collected between December 2012 and May 2013 at two university hospitals in Austria and Germany were included. Three patients had proven IPA, 14 probable IPA, and 17 possible IPA, and 44 patients had no IPA. The diagnostic accuracies of the different methods for probable/proven IPA were evaluated. The diagnostic odds ratios were the highest for the GM, PCR, and LFD tests. The sensitivities for the four methods (except culture) were between 70 and 88%. The combination of the GM (cutoff optical density index [ODI], >1.0) and LFD tests increased the sensitivity to 94%, while the combination of the GM test (>1.0) and PCR resulted in 100% sensitivity (specificity for probable/proven IPA, 95 to 98%). The performance of conventional culture was limited by low sensitivity, while that of the BDG test was limited by low specificity. We evaluated established and novel diagnostic methods for IPA and found that the Aspergillus PCR, LFD, and GM tests were the most useful methods for diagnosing the disease by using BAL fluid samples. In particular, the combination of the GM test and PCR or, if PCR is not available, the LFD test, allows for sensitive and specific diagnosis of IPA.


Assuntos
Antígenos de Fungos/análise , Aspergillus/isolamento & purificação , Líquido da Lavagem Broncoalveolar/microbiologia , DNA Fúngico/análise , Aspergilose Pulmonar Invasiva/diagnóstico , Técnicas Microbiológicas/métodos , Adulto , Idoso , Aspergillus/química , Aspergillus/crescimento & desenvolvimento , Áustria , Líquido da Lavagem Broncoalveolar/química , Cromatografia de Afinidade/métodos , Feminino , Galactose/análogos & derivados , Alemanha , Glucanos/análise , Hospitais Universitários , Humanos , Hospedeiro Imunocomprometido , Masculino , Mananas/análise , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , Estudos Prospectivos , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
18.
Ann Oncol ; 25(5): 936-47, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24399078

RESUMO

BACKGROUND: Cancer patients are at increased risk for central venous catheter-related infections (CRIs). Thus, a comprehensive, practical and evidence-based guideline on CRI in patients with malignancies is warranted. PATIENTS AND METHODS: A panel of experts by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO) has developed a guideline on CRI in cancer patients. Literature searches of the PubMed, Medline and Cochrane databases were carried out and consensus discussions were held. RESULTS: Recommendations on diagnosis, management and prevention of CRI in cancer patients are made, and the strength of the recommendation and the level of evidence are presented. CONCLUSION: This guideline is an evidence-based approach to the diagnosis, management and prevention of CRI in cancer patients.


Assuntos
Candidíase/diagnóstico , Infecções Relacionadas a Cateter/diagnóstico , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Positivas/diagnóstico , Antibacterianos/uso terapêutico , Antifúngicos/uso terapêutico , Candidíase/tratamento farmacológico , Candidíase/prevenção & controle , Infecções Relacionadas a Cateter/tratamento farmacológico , Infecções Relacionadas a Cateter/prevenção & controle , Cateterismo/métodos , Cateteres Venosos Centrais/microbiologia , Gerenciamento Clínico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/prevenção & controle , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/prevenção & controle , Hematologia , Humanos , Oncologia
19.
Eur J Radiol ; 83(1): e61-6, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24189389

RESUMO

PURPOSE: To evaluate the diagnostic accuracy of 3 Tesla proton MRI for the assessment of pneumonia/lung infiltrates in neutropenic patients with acute myeloid leukemia. MATERIAL AND METHODS: In a prospective study, 3 Tesla MRI was performed in 19 febrile neutropenic patients (5 women, 14 men; mean age 61 years ± 14.2; range 23-77 years). All patients underwent high-resolution CT less than 24h prior to MRI. The MRI protocol (Magnetom Tim Trio, Siemens) included a T2-weighted HASTE sequence (TE/TR: 49 ms/∞, slice thickness 6mm) and a high-resolution 3D VIBE sequence with an ultra-short TE<1 ms (TE/TR 0.8/2.9 ms, slice thickness 2mm). The VIBE sequence was examined before and after intravenous injection of 0.1 mmol/kg gadoterate meglumine (Dotarem, Guerbet). The presence of pulmonary abnormalities, their location within the lung, and lesion type (nodules, consolidations, glass opacity areas) were analyzed by one reader and compared to the findings of HRCT, which was evaluated by a second independent radiologist who served as the reference standard. The findings were compared per lobe in each patient and rated as true positive (TP) findings if all three characteristics (presence, location, and lesion type) listed above were concordant to HRCT. RESULTS: Pulmonary abnormalities were characterized by 3 Tesla MRI with a sensitivity of 82.3% and a specificity of 78.6%, resulting in an overall accuracy of 88% (NPV/PPV 66.7%/89.5%). In 51 lobes (19 of 19 patients), pulmonary abnormalities visualized by MR were judged to be concordant in their location and in the lesion type identified by both readers. In 22 lobes (11 of 19 patients), no abnormalities were present on either MR or HRCT (true negative). In 6 lobes (5 of 19 patients), ground glass opacity areas were detected on MRI but were not visible on HRCT (false positives). In 11 lobes (7 of 19 patients), MRI failed to detect ground glass opacity areas identified by HRCT. However, since the abnormalities were disseminated in these patients, accurate treatment decisions were possible in every case based on MRI. In one case MRI showed a central area of cavitation, which was not visualized by HRCT. CONCLUSION: Infectious nodules and consolidations can be detected in neutropenic patients with acute myeloid leukemia with a sufficient diagnostic accuracy by 3 Tesla MRI. Detection of ground glass opacity areas is the main limitation of 3-Tesla MRI when compared to HRCT.


Assuntos
Leucemia Mieloide Aguda/diagnóstico , Infiltração Leucêmica/patologia , Imageamento por Ressonância Magnética/métodos , Neutropenia/diagnóstico , Infiltração de Neutrófilos , Pneumonia/diagnóstico , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Feminino , Humanos , Leucemia Mieloide Aguda/complicações , Infiltração Leucêmica/complicações , Masculino , Pessoa de Meia-Idade , Neutropenia/complicações , Pneumonia/complicações , Prótons , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
20.
Ann Hematol ; 93(2): 317-25, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23925929

RESUMO

A reliable estimation of prognosis in patients receiving palliative care is desirable in order to facilitate clinical decision finding. For patients with advanced hematological malignancies, only few data are available to estimate prognosis of the individual's remaining life span. Here, we sought to investigate potential clinical prognostic parameters in patients with hematological malignancies admitted to a palliative care unit. Using a prospectively collected database, we analyzed clinical and laboratory parameters regarding their prognostic impact in 290 patients with malignant hematological diseases. The parameters included patient-related factors such as Eastern Cooperative Oncology Group (ECOG) performance status, need for transfusions, parenteral nutrition or analgetics, and laboratory values (hemoglobin, platelet count, lactic dehydrogenase (LDH), albumin, total protein, calcium, and C-reactive protein (CRP)) as well as referral symptoms (including anemia, infection, fever, fatigue, and dyspnea). In univariate analyses, LDH (>248 U/l), albumin corrected calcium (>2.55 mmol/l), CRP (>50 mg/l), albumin (<30 g/l), platelet count (<90 × 10(9)/l), total protein (≤60 g/l), hemoglobin (<10 g/dl), opioid treatment, performance status (ECOG >2), and need for parenteral nutrition or blood transfusion significantly correlated with impaired survival. Multivariate analysis showed that low performance status, low platelet count, opioid based pain therapy, high LDH, and low albumin were associated with poor prognosis. Using these five parameters, patients were divided into three "risk groups": low risk (presence of zero to one factor), intermediate risk (two to three factors), and high risk. Median survival for the poor risk patients was 10 days, and the intermediate and low risk patients survived a median of 63 and 440 days, respectively (p < 0.0001). Several clinical and laboratory parameters were associated with a poor prognosis of patients with hematological malignancies treated on a palliative care unit. These parameters might help clinicians to estimate prognosis of remaining life span and individualize treatment and/or end-of-life care options for patients.


Assuntos
Neoplasias Hematológicas , Cuidados Paliativos , Púrpura Trombocitopênica Idiopática , Adolescente , Adulto , Idoso , Analgésicos Opioides/administração & dosagem , Transfusão de Sangue , Bases de Dados Factuais , Intervalo Livre de Doença , Feminino , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Hemoglobinas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Nutrição Parenteral , Contagem de Plaquetas , Estudos Prospectivos , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/mortalidade , Púrpura Trombocitopênica Idiopática/terapia , Estudos Retrospectivos , Fatores de Risco , Albumina Sérica/metabolismo , Taxa de Sobrevida , Fatores de Tempo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA