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3.
Clin Microbiol Infect ; 24 Suppl 2: S2-S9, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29427801

RESUMO

BACKGROUND: The field of new biological agents is increasing exponentially over the past years, thus making prevention and management of associated infectious complications a challenge for nonspecialized clinicians. AIMS: The present consensus document is an initiative of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Compromised Hosts (ESGICH) aimed at analysing, from an infectious diseases perspective, the safety of targeted and biological therapies. SOURCES: Computer-based Medline searches with MeSH terms pertaining to each agent or therapeutic family. CONTENT: The document is structured in sections according to the targeted site of action of each drug class: proinflammatory cytokines; interleukins, immunoglobulins and other soluble immune mediators; cell surface receptors and associated signaling pathways; intracellular signaling pathways; lymphoma and leukaemia cells surface antigens; and other targeted therapies. A common outline is followed for each agent: summary of mechanism of action, approved indications and common off-label uses; expected impact on the host's susceptibility to infection; available clinical evidence (i.e. pivotal clinical trials, postmarketing studies, case series and case reports); and suggested prevention and risk minimization strategies. The methodologic and practical difficulties of assessing the specific risk posed by a given agent are also discussed. IMPLICATIONS: This ESGICH consensus document constitutes not only a comprehensive overview of the molecular rationale and clinical experience on the risk of infection associated with approved targeted therapies but also an attempt to propose a series of recommendations with the purpose of guiding physicians from different disciplines into this emerging framework.


Assuntos
Terapia Biológica/efeitos adversos , Doenças Transmissíveis/terapia , Fatores Imunológicos/efeitos adversos , Terapia de Alvo Molecular/efeitos adversos , Animais , Anticorpos Monoclonais/uso terapêutico , Terapia Biológica/métodos , Doenças Transmissíveis/imunologia , Citocinas/efeitos adversos , Citocinas/uso terapêutico , Humanos , Hospedeiro Imunocomprometido , Fatores Imunológicos/administração & dosagem , Camundongos , Terapia de Alvo Molecular/métodos , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/uso terapêutico
4.
BMJ Open ; 7(1): e013268, 2017 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-28115333

RESUMO

INTRODUCTION: Bloodstream infection (BSI) due to extended-spectrum ß-lactamase-producing Gram-negative bacilli (ESBL-GNB) is increasing at an alarming pace worldwide. Although ß-lactam/ß-lactamase inhibitor (BLBLI) combinations have been suggested as an alternative to carbapenems for the treatment of BSI due to these resistant organisms in the general population, their usefulness for the treatment of BSI due to ESBL-GNB in haematological patients with neutropaenia is yet to be elucidated. The aim of the BICAR study is to compare the efficacy of BLBLI combinations with that of carbapenems for the treatment of BSI due to an ESBL-GNB in this population. METHODS AND ANALYSIS: A multinational, multicentre, observational retrospective study. Episodes of BSI due to ESBL-GNB occurring in haematological patients and haematopoietic stem cell transplant recipients with neutropaenia from 1 January 2006 to 31 March 2015 will be analysed. The primary end point will be case-fatality rate within 30 days of onset of BSI. The secondary end points will be 7-day and 14-day case-fatality rates, microbiological failure, colonisation/infection by resistant bacteria, superinfection, intensive care unit admission and development of adverse events. SAMPLE SIZE: The number of expected episodes of BSI due to ESBL-GNB in the participant centres will be 260 with a ratio of control to experimental participants of 2. ETHICS AND DISSEMINATION: The protocol of the study was approved at the first site by the Research Ethics Committee (REC) of Hospital Universitari de Bellvitge. Approval will be also sought from all relevant RECs. Any formal presentation or publication of data from this study will be considered as a joint publication by the participating investigators and will follow the recommendations of the International Committee of Medical Journal Editors (ICMJE). The study has been endorsed by the European Study Group for Bloodstream Infection and Sepsis (ESGBIS) and the European Study Group for Infections in Compromised Hosts (ESGICH).


Assuntos
Antibacterianos/uso terapêutico , Infecções por Enterobacteriaceae/tratamento farmacológico , Neutropenia/complicações , Inibidores de beta-Lactamases/uso terapêutico , beta-Lactamas/uso terapêutico , Adolescente , Adulto , Idoso , Bacteriemia/tratamento farmacológico , Quimioterapia Combinada , Feminino , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Superinfecção/prevenção & controle
5.
Transpl Infect Dis ; 17(5): 637-46, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26134282

RESUMO

BACKGROUND: This study aimed to characterize the dynamics of acquisition of cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) in CMV donor positive/recipient negative solid organ transplant (SOT) patients receiving long-term antiviral prophylaxis, and to determine whether development of CMI confers protection against CMV disease. METHODS: A prospective multicenter study was conducted in Spain from September 2009 to September 2012. Whole blood specimens were prospectively collected at 30, 90, 120, 200, and 365 days after SOT, and CMI was determined by enumeration of CMV pp65 and IE-1-specific CD69(+) /interferon-γ-producing CD8(+) and CD4(+) T cells by flow cytometry for intracellular cytokine staining. As part of a simultaneous clinical trial, patients received either early prophylaxis (in the first 3 days after transplantation) in the first period of the study or delayed prophylaxis (initiated at day 14) during the second period of the study. The impact of the dynamics of acquisition of CMV-specific CMI on the incidence of CMV disease was evaluated by Kaplan-Meier survival analysis. RESULTS: A total of 95 SOT recipients were recruited. CMV infection and disease occurred in 38 (40%) and 26 (27.4%) patients, respectively. The proportion of patients achieving any detectable CMV-specific CMI response at each of the different monitoring points was higher in liver transplant recipients, as compared to kidney or heart transplant recipients. The presence of any detectable response at day 120 or 200 was protective against the development of CMV disease (positive predictive values 92% and 93%, respectively). CONCLUSIONS: The rate of acquisition of CMV-specific CMI in SOT recipients undergoing antiviral prophylaxis differed significantly between different SOT populations. Patients developing any detectable CMI response were protected against the occurrence of CMV disease.


Assuntos
Antivirais/uso terapêutico , Infecções por Citomegalovirus/prevenção & controle , Citomegalovirus/imunologia , Ganciclovir/análogos & derivados , Imunidade Celular , Transplante de Órgãos , Complicações Pós-Operatórias/prevenção & controle , Adulto , Idoso , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/virologia , Feminino , Seguimentos , Ganciclovir/uso terapêutico , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios/métodos , Complicações Pós-Operatórias/imunologia , Complicações Pós-Operatórias/virologia , Estudos Prospectivos , Resultado do Tratamento , Valganciclovir
6.
J Infect ; 71(5): 561-70, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26183297

RESUMO

OBJECTIVES: Evaluate the protective effect against late CMV disease of delaying antiviral prophylaxis initiation in D+/R- patients receiving solid organ transplant (SOT). METHODS: Prospective multicenter study in D+/R- SOT recipients in Spain (Sept/09-Sept/12). Whole blood specimens were prospectively collected after Tx for CMV-specific cell-mediated immunity (CMI) determination. Two prophylaxis strategies were compared: early prophylaxis (EP; starting within the first 3 days after Tx) and delayed prophylaxis (DP; starting 14 days after Tx). Risk factors for the occurrence of CMV disease were determined by survival analysis and proportional risk Cox regression models. RESULTS: We included 95 patients (50 EP V 45 DP). Twenty six patients (27.4%) developed CMV disease: 32.7% EP vs. 20% DP; (p = 0.2). No cases of CMV disease were reported previously to beginning delayed prophylaxis. The percentage of individuals with detectable CMI response was higher in patients with DP although differences did not reach statistic significance (42% vs 29.6% at day 200 after Tx; p = 0.4). There was a clear trend towards less end-organ CMV disease in patients receiving DP (18.2% EP vs 5% DP; p = 0.09) and DP was the only protective factor in the multivariate analysis (HR: 0.26; CI: 0.05-1.2; p = 0.09). CONCLUSIONS: A 14-day delay in CMV prophylaxis in D+/R- SOT recipients is safe and may reduce the incidence of late CMV end-organ disease although correlation of this effect with CMI responses was not complete.


Assuntos
Antivirais/uso terapêutico , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/prevenção & controle , Citomegalovirus/imunologia , Ganciclovir/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Transplantados , Citomegalovirus/efeitos dos fármacos , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/virologia , Feminino , Humanos , Imunidade Celular , Incidência , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Espanha/epidemiologia , Análise de Sobrevida
7.
J Antimicrob Chemother ; 69(11): 3134-41, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24970743

RESUMO

BACKGROUND: New techniques, such as those based on multiplex quantitative real-time PCR (MRT-PCR), can improve the detection of invasive candidiasis (IC). METHODS: We prospectively studied 63 intensive care unit patients with suspected IC and 40 healthy controls. Blood cultures and MRT-PCR were performed at day 0 and +2, +7, +14 and +21 days in all patients. In addition, ß-d-glucan (BDG) and Candida albicans germ tube antibody (CAGTA) were quantified. RESULTS: IC was confirmed in 27 patients. Colonization was significantly higher in patients with IC (96% versus 64%, P = 0.002). The sensitivity, specificity, positive predictive value and negative predictive value of MRT-PCR for the diagnosis of IC were 96.3%, 97.3%, 92.8% and 98.7%, respectively. The positive predictive value and specificity were significantly higher for MRT-PCR than for BDG and CATGA. MRT-PCR performed very well, especially in deep-seated IC (sensitivity 90.9% versus 45.4% for blood culture; P = 0.06). As regards the most appropriate clinical sample for DNA amplification, in this study whole blood and serum presented similar results. CONCLUSIONS: MRT-PCR appears to be a useful test for confirming a diagnosis of IC in critically ill patients, especially in those with deep-seated disease. Its high sensitivity and positive predictive value make it a much more efficient tool for the management of IC than other diagnostic procedures and clinical scores.


Assuntos
Candidíase Invasiva/sangue , Candidíase Invasiva/diagnóstico , Unidades de Terapia Intensiva/normas , Reação em Cadeia da Polimerase em Tempo Real/normas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto Jovem
8.
Transpl Infect Dis ; 16(3): 387-96, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24807640

RESUMO

BACKGROUND: Cytomegalovirus (CMV)-negative recipients of a graft from a CMV-positive donor (D+/R-) are at high risk of CMV disease. Current preventive strategies include universal prophylaxis (UP) and preemptive therapy (PT). However, the best strategy to prevent CMV disease and achieve better long-term outcomes remains a matter of debate. METHODS: We analyzed the incidence of CMV disease and long-term outcomes including graft dysfunction and patient mortality at 5 years after transplantation with both preventive strategies. High-risk (D+/R-) kidney and liver transplant recipients from the RESITRA cohort were included. RESULTS: Of 2410 kidney or liver transplant patients, 195 (8.3%) were D+/R-. The final cohort included 58 liver and 102 kidney recipients. UP was given in 92 patients and 68 received PT; 10.9% and 36.8% developed CMV disease, respectively (P < 0.01). The independent risk factors for CMV disease were PT strategy (hazard ratio [HR], 3.30; 95% confidence interval [CI], 1.6-6.9), kidney transplantation (HR, 3.8; 95% CI, 1.4-9.9), and cyclosporine immunosuppression (HR, 2.4; 95% CI, 1.2-4.7). PT strategy was also a risk factor for CMV disease in both liver transplantation (HR, 11.0; 95% CI, 1.2-98.7) and kidney transplantation (HR, 2.7; 95% CI, 1.3-6.0), independently. The development of CMV replication during the first 2 years after transplantation was a risk factor for graft dysfunction at 5 years after transplantation (odds ratio, 3.4; 95% CI, 1.3-9.0). Nevertheless, no significant differences were seen in either graft dysfunction or mortality between the 2 strategies. CONCLUSIONS: The study supports the benefit of the UP strategy to prevent CMV disease in D+/R- liver or kidney transplant patients. The development of CMV replication during the first 2 years after transplantation was associated with graft dysfunction at 5 years after transplantation.


Assuntos
Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/prevenção & controle , Ganciclovir/análogos & derivados , Ganciclovir/farmacologia , Transplante de Rim/efeitos adversos , Transplante de Fígado/efeitos adversos , Adulto , Antivirais/farmacologia , Estudos de Coortes , Citomegalovirus/fisiologia , Feminino , Humanos , Imunossupressores , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Valganciclovir , Replicação Viral , Adulto Jovem
9.
Clin Microbiol Infect ; 20 Suppl 7: 27-48, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24810152

RESUMO

Solid organ transplant (SOT) recipients have a significant risk of invasive fungal diseases (IFD) caused mainly by Candida spp. and Aspergillus spp. Candida spp. is the most frequent agent of IFD in the transplant recipient. The absence of clinical trials and the epidemiological differences in IFD in different transplant programmes mean that there are no definitive recommendations for the diagnosis, treatment and prevention of IFD in SOT, so most of the evidence must be based on clinical experience.


Assuntos
Candidíase Invasiva/epidemiologia , Aspergilose Pulmonar Invasiva/epidemiologia , Infecções Oportunistas/epidemiologia , Transplante de Órgãos , Transplantados , Candidíase Invasiva/diagnóstico , Candidíase Invasiva/prevenção & controle , Candidíase Invasiva/terapia , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/uso terapêutico , Aspergilose Pulmonar Invasiva/diagnóstico , Aspergilose Pulmonar Invasiva/prevenção & controle , Aspergilose Pulmonar Invasiva/terapia , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/prevenção & controle , Infecções Oportunistas/terapia
10.
Clin Microbiol Infect ; 20 Suppl 7: 89-101, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24707957

RESUMO

Mycobacterial infections represent a growing challenge for solid organ transplant recipients (SOT). The adverse effects of tuberculosis (TB) therapy present a major difficulty, due to the interactions with immunosuppressive drugs and direct drug toxicity. While TB may be donor-transmitted or community-acquired, it usually develops at a latent infection site in the recipient. Pre-transplant prevention efforts will improve transplant outcomes and avoid the complications associated with post-transplant diagnosis and treatment. The present review and consensus manuscript is based on the updated published information and expert recommendations. The current data about epidemiology, diagnosis, new regimens for the treatment of latent TB infection (LTBI), the experience with rifamycins for the treatment of active TB in the post-transplant period and the experience with isoniazid for LTBI in the liver transplant population, are also reviewed. We attempt to provide useful recommendations for each transplant period and problem concerning mycobacterial infections in SOT recipients.


Assuntos
Infecções Oportunistas/epidemiologia , Infecções Oportunistas/prevenção & controle , Transplante de Órgãos , Transplantados , Tuberculose/tratamento farmacológico , Antituberculosos/uso terapêutico , Interações Medicamentosas , Farmacorresistência Bacteriana , Tratamento Farmacológico/métodos , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/uso terapêutico , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/terapia , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Tuberculose/prevenção & controle
11.
Clin Microbiol Infect ; 20 Suppl 7: 10-8, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24476053

RESUMO

In the context of solid organ transplantation, screening of recipients and organ donors is crucial, and should be performed with great rigour to minimize the reactivation or the risk of transmission of certain infectious processes. This review aims to update understanding of the possible pathologies involved, as well as of emerging infections that, as a result of globalization, are gaining increasing prominence on a daily basis.


Assuntos
Doenças Transmissíveis/transmissão , Transmissão de Doença Infecciosa/prevenção & controle , Controle de Infecções/métodos , Programas de Rastreamento/métodos , Transplante de Órgãos/efeitos adversos , Doadores de Tecidos , Doenças Transmissíveis Emergentes/prevenção & controle , Humanos , Transplantados
12.
J Infect ; 65(1): 64-70, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22369861

RESUMO

The clinical presentation and outcome of candidemia has changed in recent years. We compared two 5-year periods (2000-2004 and 2005-2009) in a single institution. We recorded 419 candidemia episodes during the study period (124 in the first period and 295 in the second period). We observed a significant increase in the number of cases per 1000 admissions per year, from 0.57 in 2000 to 1.52 in 2009 (χ(2) LT <0.001). Candida albicans was the most frequently isolated species (42.2%), followed by Candida parapsilosis (34.4%) and Candida glabrata (12.9%). In the second period, episodes were associated with higher comorbidity and were more commonly nosocomial, with a more frequent catheter-related source and an increased rate of C. glabrata infection. No significant differences were observed in susceptibility by species during the study period. According to multivariate analysis, the independent factors associated with higher mortality were shock, age >50 years, elevated comorbidity score (Charlson index >6), and source of candidemia other than catheter. In contrast to the increase in comorbid conditions observed in recent years, mortality remained similar during both periods (~37% during the first month). This finding could be attributed to a significant increase in catheter-related candidemia and better outcome, as well as to a potential improvement in the management of antifungal therapy in recent years.


Assuntos
Candidemia/epidemiologia , Candidemia/mortalidade , Idoso , Idoso de 80 Anos ou mais , Candida/classificação , Candida/isolamento & purificação , Candidemia/microbiologia , Candidemia/patologia , Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/microbiologia , Infecções Relacionadas a Cateter/mortalidade , Infecções Relacionadas a Cateter/patologia , Comorbidade , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Infecção Hospitalar/mortalidade , Infecção Hospitalar/patologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Análise de Sobrevida , Resultado do Tratamento
13.
Transpl Infect Dis ; 13(2): 204-7, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21457423

RESUMO

We report the case of a 72-year-old female renal transplant recipient with a nodular lesion in the distal phalange of the third left finger produced by a dematiaceous fungus that was identified as Phomopsis longicolla. She was treated with itraconazole and terbinafine and later with voriconazole, without response. The patient underwent a surgical resection with lesion-free edge and continued on voriconazole. One year later she was asymptomatic and had not developed new lesions.


Assuntos
Ascomicetos/isolamento & purificação , Dermatomicoses/microbiologia , Transplante de Rim/efeitos adversos , Idoso , Antifúngicos/uso terapêutico , Dermatomicoses/tratamento farmacológico , Dermatomicoses/epidemiologia , Dermatomicoses/etiologia , Feminino , Guiné/epidemiologia , Humanos , Espanha/epidemiologia
16.
Am J Transplant ; 10(7): 1511-6, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20642677

RESUMO

The clinical application of xenotransplantation poses immunologic, ethical, and microbiologic challenges. Significant progress has been made in the investigation of each of these areas. Among concerns regarding infectious risks for human xenograft recipients is the identification in swine of infectious agents including porcine endogenous retroviruses (PERV) that are capable of replication in some human cell lines. PERV replication has, however, been difficult to demonstrate in primate-derived cell lines and in preclinical studies of non-human primates receiving porcine xenografts. Endogenous 'retroviral restriction factors' are intracellular proteins and components of the innate immune system that act at various steps in retroviral replication. Recent studies suggest that some of these factors may have applications in the management of endogenous retroviruses in xenotransplantation. The risks of PERV infection and the potential role of retroviral restriction factors in xenotransplantation are reviewed in detail.


Assuntos
Infecções/epidemiologia , Infecções por Retroviridae/epidemiologia , Retroviridae/isolamento & purificação , Transplante Heterólogo/efeitos adversos , Animais , Antígenos CD/fisiologia , Retrovirus Endógenos/patogenicidade , Proteínas Ligadas por GPI , Genoma Viral , Humanos , Estágios do Ciclo de Vida , Glicoproteínas de Membrana/fisiologia , Retroviridae/genética , Retroviridae/fisiologia , Infecções por Retroviridae/prevenção & controle , Fatores de Risco , Suínos , Transplante Heterólogo/métodos
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