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1.
Lancet Oncol ; 22(6): e254-e269, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33811813

RESUMO

Paediatric patients with cancer and those undergoing allogeneic haematopoietic cell transplantation have an increased susceptibility to invasive fungal diseases. In addition to differences in underlying conditions and comorbidities relative to adults, invasive fungal diseases in infants, children, and adolescents are unique in terms of their epidemiology, the validity of current diagnostic methods, the pharmacology and dosing of antifungal agents, and the absence of phase 3 clinical trials to provide data to guide evidence-based interventions. To re-examine the state of knowledge and to further improve invasive fungal disease diagnosis, prevention, and management, the 8th European Conference on Infections in Leukaemia (ECIL-8) reconvened a Paediatric Group to review the literature and to formulate updated recommendations according to the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and European Confederation of Medical Mycology (ECMM) grading system, which are summarised in this Review.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia/terapia , Micoses/terapia , Antifúngicos/uso terapêutico , Congressos como Assunto , Guias como Assunto , Humanos , Leucemia/complicações , Leucemia/epidemiologia , Leucemia/microbiologia , Micoses/complicações , Micoses/epidemiologia , Micoses/microbiologia , Pediatria/tendências
2.
Pediatr Dermatol ; 37(3): 476-479, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32115769

RESUMO

BACKGROUND: Molluscum contagiosum (MC) is a common skin infection in the pediatric age group. The infection is self-limited and manifests as discrete, umbilicated skin-colored papules on any skin surface of the body. At times, complications such as local dermatitis and swelling, erythema, and pus formation may appear. These signs of inflammation are commonly presumed to represent bacterial infection. METHODS: This multicenter study was a retrospective analysis of data collected on all patients diagnosed with inflamed lesions secondary to MC and treated at the Hadassah Medical Centers and Shaare Zedek Medical Center in Jerusalem, Israel, from 1/1/2008 to 1/07/2018. Characteristics of children with positive cultures were compared to those with negative cultures and those with contaminants. RESULTS: A total of 56 cases were reviewed; the mean age at presentation was 4.6 years. Fever was reported in 12.5%, and 62.5% received systemic antibiotics because of their inflamed MC prior to admission. Fifty-five percent had sterile cultures or cultures growing only contaminants. Only seven had positive cultures with the common cutaneous pathogens. No statistical difference was observed between the patients with pathogenic isolates and patients with sterile or non-pathogenic cultures in terms of demographics, lesion characteristics, inflammatory markers, or length of hospitalization. CONCLUSION: The findings suggest that most cases of suspected MC-related secondary infection can be attributed to inflammation rather than to bacterial infection. However, in some cases, true bacterial infection should be suspected and treated accordingly.


Assuntos
Molusco Contagioso , Criança , Eritema , Humanos , Israel/epidemiologia , Molusco Contagioso/diagnóstico , Estudos Retrospectivos , Pele
3.
Eur J Clin Microbiol Infect Dis ; 38(3): 505-514, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30707378

RESUMO

Respiratory tract infections (RTI) are more commonly caused by viral pathogens in children than in adults. Surprisingly, little is known about antibiotic use in children as compared to adults with RTI. This prospective study aimed to determine antibiotic misuse in children and adults with RTI, using an expert panel reference standard, in order to prioritise the target age population for antibiotic stewardship interventions. We recruited children and adults who presented at the emergency department or were hospitalised with clinical presentation of RTI in The Netherlands and Israel. A panel of three experienced physicians adjudicated a reference standard diagnosis (i.e. bacterial or viral infection) for all the patients using all available clinical and laboratory information, including a 28-day follow-up assessment. The cohort included 284 children and 232 adults with RTI (median age, 1.3 years and 64.5 years, respectively). The proportion of viral infections was larger in children than in adults (209(74%) versus 89(38%), p < 0.001). In case of viral RTI, antibiotics were prescribed (i.e. overuse) less frequently in children than in adults (77/209 (37%) versus 74/89 (83%), p < 0.001). One (1%) child and three (2%) adults with bacterial infection were not treated with antibiotics (i.e. underuse); all were mild cases. This international, prospective study confirms major antibiotic overuse in patients with RTI. Viral infection is more common in children, but antibiotic overuse is more frequent in adults with viral RTI. Together, these findings support the need for effective interventions to decrease antibiotic overuse in RTI patients of all ages.


Assuntos
Antibacterianos/uso terapêutico , Gestão de Antimicrobianos/normas , Prescrição Inadequada/estatística & dados numéricos , Infecções Respiratórias/tratamento farmacológico , Idoso , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/epidemiologia , Pré-Escolar , Feminino , Humanos , Lactente , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Estudos Prospectivos , Padrões de Referência , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/epidemiologia , Viroses/diagnóstico , Viroses/tratamento farmacológico , Viroses/epidemiologia
4.
Clin Infect Dis ; 65(11): 1819-1828, 2017 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-29020364

RESUMO

BACKGROUND: This intercontinental study aimed to study gram-negative rod (GNR) resistance in hematopoietic stem cell transplantation (HSCT). METHODS: GNR bacteremias occurring during 6 months post-HSCT (February 2014-May 2015) were prospectively collected, and analyzed for rates and risk factors for resistance to fluoroquinolones, noncarbapenem anti-Pseudomonas ß-lactams (noncarbapenems), carbapenems, and multidrug resistance. RESULTS: Sixty-five HSCT centers from 25 countries in Europe, Australia, and Asia reported data on 655 GNR episodes and 704 pathogens in 591 patients (Enterobacteriaceae, 73%; nonfermentative rods, 24%; and 3% others). Half of GNRs were fluoroquinolone and noncarbapenem resistant; 18.5% carbapenem resistant; 35.2% multidrug resistant. The total resistance rates were higher in allogeneic HSCT (allo-HSCT) vs autologous HSCT (auto-HSCT) patients (P < .001) but similar in community-acquired infections. Noncarbapenem resistance and multidrug resistance were higher in auto-HSCT patients in centers providing vs not providing fluoroquinolone prophylaxis (P < .01). Resistance rates were higher in southeast vs northwest Europe and similar in children and adults, excluding higher fluoroquinolone- and ß-lactam/ß-lactamase inhibitor resistance rates in allo-HSCT adults. Non-Klebsiella Enterobacteriaceae were rarely carbapenem resistant. Multivariable analysis revealed resistance risk factors in allo-HSCT patients: fluoroquinolone resistance: adult, prolonged neutropenia, breakthrough on fluoroquinolones; noncarbapenem resistance: hospital-acquired infection, breakthrough on noncarbapenems or other antibiotics (excluding fluoroquinolones, noncarbapenems, carbapenems), donor type; carbapenem resistance: breakthrough on carbapenem, longer hospitalization, intensive care unit, previous other antibiotic therapy; multidrug resistance: longer hospitalization, breakthrough on ß-lactam/ß-lactamase inhibitors, and carbapenems. Inappropriate empiric therapy and mortality were significantly more common in infections caused by resistant bacteria. CONCLUSIONS: Our data question the recommendation for fluoroquinolone prophylaxis and call for reassessment of local empiric antibiotic protocols. Knowledge of pathogen-specific resistance enables early appropriate empiric therapy. Monitoring of resistance is crucial. CLINICAL TRIALS REGISTRATION: NCT02257931.


Assuntos
Antibacterianos/farmacologia , Bacteriemia/microbiologia , Farmacorresistência Bacteriana Múltipla , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/microbiologia , Transplante de Células-Tronco Hematopoéticas , Transplantados , Adolescente , Adulto , Idoso , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/epidemiologia , Criança , Pré-Escolar , Europa (Continente)/epidemiologia , Feminino , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/epidemiologia , Humanos , Lactente , Internacionalidade , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Transplantados/estatística & dados numéricos , Adulto Jovem
5.
Haematologica ; 101(7): 803-11, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27365460

RESUMO

Epstein-Barr virus-related post-transplant lymphoproliferative disorders are recognized as a significant cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation. To better define current understanding of post-transplant lymphoproliferative disorders in stem cell transplant patients, and to improve its diagnosis and management, a working group of the Sixth European Conference on Infections in Leukemia 2015 reviewed the literature, graded the available quality of evidence, and developed evidence-based recommendations for diagnosis, prevention, prophylaxis and therapy of post-transplant lymphoproliferative disorders exclusively in the stem cell transplant setting. The key elements in diagnosis include non-invasive and invasive methods. The former are based on quantitative viral load measurement and imaging with positron emission tomography; the latter with tissue biopsy for histopathology and detection of Epstein-Barr virus. The diagnosis of post-transplant lymphoproliferative disorder can be established on a proven or probable level. Therapeutic strategies include prophylaxis, preemptive therapy and targeted therapy. Rituximab, reduction of immunosuppression and Epstein-Barr virus-specific cytotoxic T-cell therapy are recommended as first-line therapy, whilst unselected donor lymphocyte infusions or chemotherapy are options as second-line therapy; other methods including antiviral drugs are discouraged.


Assuntos
Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/terapia , Gerenciamento Clínico , Infecções por Vírus Epstein-Barr/epidemiologia , Infecções por Vírus Epstein-Barr/prevenção & controle , Humanos , Transtornos Linfoproliferativos/epidemiologia , Guias de Prática Clínica como Assunto , Fatores de Risco
6.
Acta Paediatr ; 105(4): e156-60, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26709717

RESUMO

AIM: Data on antimicrobial resistance in uropathogens in infants up to the age of three months are limited. This study characterised resistance patterns in Gram-negative uropathogens in infants up to the age of two months. METHODS: Previously healthy young infants with urinary tract infections (UTIs) were studied retrospectively. Antimicrobial susceptibility was evaluated. Multidrug resistance (MDR) was defined as resistance to at least three antibiotic classes. Clinical, laboratory and outcome data were compared between infants with UTIs caused by bacteria sensitive and resistant to empirical and to oral therapy. RESULTS: We evaluated 306 UTI episodes with 314 pathogens. The following resistance rates were observed: ampicillin 73.7%, cefazoline 22.1%, ampicillin/clavulanate 21.8%, cefuroxime 7.8%, gentamicin 7%; MDR 11.8%; resistant to empirical treatment 7.3% and resistant to available oral antibiotics 8.6%. Our study showed that pathogens resistant to empirical and oral therapy were more frequently isolated in non-Jewish (Arab) infants and in those of ≥30 days of age. Resistance to empirical treatment and oral antibiotics also resulted in longer mean hospital stays. CONCLUSION: Resistance to antibiotics challenges empirical therapy and compromises oral treatment options in young infants with UTIs. Antimicrobial resistance patterns should be monitored in infants to determine appropriate empirical antibiotic therapy protocols.


Assuntos
Farmacorresistência Bacteriana , Infecções Urinárias/tratamento farmacológico , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Infecções Urinárias/microbiologia
7.
Infection ; 43(6): 663-70, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25929419

RESUMO

PURPOSE: This study aimed at reviewing our experience with infections caused by Fusobacterium in children. METHODS: A retrospective analysis of medical records of children admitted to Hadassah-Hebrew University Medical Center from 2000 to 2013, in whom Fusobacterium spp. was identified in any specimen. RESULTS: A total of 22 patients (males = 12) at a mean ± SE age of 5 ± 1 (range 1-17) years, were identified. The most common complication was abscess formation (n = 11, 50 %). Eight children (36.4 %) had intracranial complications, including brain abscess (n = 4), meningitis (n = 4) and cerebral sinus vein thrombosis (CSVT, n = 5). Seventeen children (77 %) had bacteremia. Primary site of infection was otogenic (n = 9), oropharyngeal (n = 7), respiratory (n = 2), sinuses (n = 2), intra-abdominal (n = 1) and mucositis (n = 1). Fourteen cases were caused by Fusobacterium necrophorum, including four cases with CSVT, 7/8 cases of mastoiditis, four of them with subperiosteal abscess formation; all four cases with meningitis and two brain abscesses. Fifteen (68 %) patients required surgical intervention and 3 (14 %) received anti-coagulation therapy. Excluding one patient with overwhelming sepsis with fatal outcome, all patients recovered. CONCLUSIONS: Fusobacterium infections in children can cause a diverse spectrum of disease and is associated with high rates of abscess formation and intracranial complications. Although Fusobacterium nucleatum is abundant in the oral cavity, F. necrophorum is the main pathogen that causes severe infections in healthy children.


Assuntos
Infecções por Fusobacterium/epidemiologia , Infecções por Fusobacterium/patologia , Fusobacterium necrophorum/isolamento & purificação , Abscesso/epidemiologia , Abscesso/microbiologia , Abscesso/patologia , Adolescente , Criança , Pré-Escolar , Feminino , Infecções por Fusobacterium/microbiologia , Humanos , Lactente , Israel/epidemiologia , Masculino , Estudos Retrospectivos
8.
Euro Surveill ; 20(44)2015.
Artigo em Inglês | MEDLINE | ID: mdl-26558845

RESUMO

During the current outbreak of Ebola virus disease (EVD) in West Africa, preventing exportation of the disease posed many challenges for economically more developed countries. In Israel, although the risk of importing single cases was assumed to be low, the implications of local transmission were great. This article describes the EVD preparedness plan of the Israeli Ministry of Health. Key elements were a sensitive case definition, designation of a single treatment centre for suspected and confirmed cases, construction of a mobile unit using customised negative-pressure tents and a vigorous national training programme. There were no patients with EVD in Israel, but a few suspected cases were assessed. The Israeli plan may provide a template for emergency infectious disease response in other geographically small countries.


Assuntos
Controle de Doenças Transmissíveis/organização & administração , Planejamento em Desastres/organização & administração , Doença pelo Vírus Ebola/prevenção & controle , Vigilância em Saúde Pública/métodos , Gestão da Segurança/organização & administração , África Ocidental/epidemiologia , Surtos de Doenças/prevenção & controle , Ebolavirus , Humanos , Israel/epidemiologia , Medição de Risco , Gestão de Riscos , Viagem
9.
Lancet Oncol ; 15(8): e327-40, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24988936

RESUMO

Invasive opportunistic fungal diseases (IFDs) are important causes of morbidity and mortality in paediatric patients with cancer and those who have had an allogeneic haemopoietic stem-cell transplantation (HSCT). Apart from differences in underlying disorders and comorbidities relative to those of adults, IFDs in infants, children, and adolescents are unique with respect to their epidemiology, the usefulness of diagnostic methods, the pharmacology and dosing of antifungal agents, and the absence of interventional phase 3 clinical trials for guidance of evidence-based decisions. To better define the state of knowledge on IFDs in paediatric patients with cancer and allogeneic HSCT and to improve IFD diagnosis, prevention, and management, the Fourth European Conference on Infections in Leukaemia (ECIL-4) in 2011 convened a group that reviewed the scientific literature on IFDs and graded the available quality of evidence according to the Infectious Diseases Society of America grading system. The final considerations and recommendations of the group are summarised in this manuscript.


Assuntos
Antifúngicos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia/complicações , Micoses/diagnóstico , Micoses/tratamento farmacológico , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Humanos , Lactente , Micoses/epidemiologia , Micoses/etiologia , Micoses/prevenção & controle , Infecções Oportunistas/epidemiologia , Infecções Oportunistas/etiologia , Infecções Oportunistas/prevenção & controle , Transplante Homólogo
10.
Blood ; 119(17): 3997-4008, 2012 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-22403255

RESUMO

T follicular helper (Tfh) cells are critical for providing the necessary signals to induce differentiation of B cells into memory and Ab-secreting cells. Accordingly, it is important to identify the molecular requirements for Tfh cell development and function. We previously found that IL-12 mediates the differentiation of human CD4(+) T cells to the Tfh lineage, because IL-12 induces naive human CD4(+) T cells to acquire expression of IL-21, BCL6, ICOS, and CXCR5, which typify Tfh cells. We have now examined CD4(+) T cells from patients deficient in IL-12Rß1, TYK2, STAT1, and STAT3 to further explore the pathways involved in human Tfh cell differentiation. Although STAT1 was dispensable, mutations in IL12RB1, TYK2, or STAT3 compromised IL-12-induced expression of IL-21 by human CD4(+) T cells. Defective expression of IL-21 by STAT3-deficient CD4(+) T cells resulted in diminished B-cell helper activity in vitro. Importantly, mutations in STAT3, but not IL12RB1 or TYK2, also reduced Tfh cell generation in vivo, evidenced by decreased circulating CD4(+)CXCR5(+) T cells. These results highlight the nonredundant role of STAT3 in human Tfh cell differentiation and suggest that defective Tfh cell development and/or function contributes to the humoral defects observed in STAT3-deficient patients.


Assuntos
Diferenciação Celular , Interleucina-12/farmacologia , Mutação/genética , Receptores de Interleucina-12/genética , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT3/genética , Linfócitos T Auxiliares-Indutores/citologia , TYK2 Quinase/genética , Animais , Linfócitos B/citologia , Linfócitos B/imunologia , Linfócitos B/metabolismo , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Células Cultivadas , Citocinas/metabolismo , Humanos , Hospedeiro Imunocomprometido , Ativação Linfocitária , Camundongos , Receptores de Interleucina-12/deficiência , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT3/deficiência , Transdução de Sinais , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/metabolismo , TYK2 Quinase/metabolismo , Fatores de Transcrição/metabolismo
11.
J Allergy Clin Immunol ; 132(2): 400-11.e9, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23830147

RESUMO

BACKGROUND: The capacity of CD8(+) T cells to control infections and mediate antitumor immunity requires the development and survival of effector and memory cells. IL-21 has emerged as a potent inducer of CD8(+) T-cell effector function and memory development in mouse models of infectious disease. However, the role of IL-21 and associated signaling pathways in protective CD8(+) T-cell immunity in human subjects is unknown. OBJECTIVE: We sought to determine which signaling pathways mediate the effects of IL-21 on human CD8(+) T cells and whether defects in these pathways contribute to disease pathogenesis in patients with primary immunodeficiencies caused by mutations in components of the IL-21 signaling cascade. METHODS: Human primary immunodeficiencies resulting from monogenic mutations provide a unique opportunity to assess the requirement for particular molecules in regulating human lymphocyte function. Lymphocytes from patients with loss-of-function mutations in signal transducer and activator of transcription 1 (STAT1), STAT3, or IL-21 receptor (IL21R) were used to assess the respective roles of these genes in human CD8(+) T-cell differentiation in vivo and in vitro. RESULTS: Mutations in STAT3 and IL21R, but not STAT1, led to a decrease in multiple memory CD8(+) T-cell subsets in vivo, indicating that STAT3 signaling, possibly downstream of IL-21R, regulates the memory cell pool. Furthermore, STAT3 was important for inducing the lytic machinery in IL-21-stimulated naive CD8(+) T cells. However, this defect was overcome by T-cell receptor engagement. CONCLUSION: The IL-21R/STAT3 pathway is required for many aspects of human CD8(+) T-cell behavior but in some cases can be compensated by other signals. This helps explain the relatively mild susceptibility to viral disease observed in STAT3- and IL-21R-deficient subjects.


Assuntos
Linfócitos T CD8-Positivos/citologia , Diferenciação Celular , Memória Imunológica , Síndrome de Job/genética , Mutação , Fator de Transcrição STAT3/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Humanos , Interleucinas/genética , Interleucinas/imunologia , Interleucinas/metabolismo , Síndrome de Job/imunologia , Síndrome de Job/patologia , Receptores de Interleucina-21/genética , Receptores de Interleucina-21/imunologia , Receptores de Interleucina-21/metabolismo , Fator de Transcrição STAT3/genética
12.
Haematologica ; 98(12): 1826-35, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24323983

RESUMO

Owing to increasing resistance and the limited arsenal of new antibiotics, especially against Gram-negative pathogens, carefully designed antibiotic regimens are obligatory for febrile neutropenic patients, along with effective infection control. The Expert Group of the 4(th) European Conference on Infections in Leukemia has developed guidelines for initial empirical therapy in febrile neutropenic patients, based on: i) the local resistance epidemiology; and ii) the patient's risk factors for resistant bacteria and for a complicated clinical course. An 'escalation' approach, avoiding empirical carbapenems and combinations, should be employed in patients without particular risk factors. A 'de-escalation' approach, with initial broad-spectrum antibiotics or combinations, should be used only in those patients with: i) known prior colonization or infection with resistant pathogens; or ii) complicated presentation; or iii) in centers where resistant pathogens are prevalent at the onset of febrile neutropenia. In the latter case, infection control and antibiotic stewardship also need urgent review. Modification of the initial regimen at 72-96 h should be based on the patient's clinical course and the microbiological results. Discontinuation of antibiotics after 72 h or later should be considered in neutropenic patients with fever of unknown origin who are hemodynamically stable since presentation and afebrile for at least 48 h, irrespective of neutrophil count and expected duration of neutropenia. This strategy aims to minimize the collateral damage associated with antibiotic overuse, and the further selection of resistance.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana/fisiologia , Febre/tratamento farmacológico , Leucemia/tratamento farmacológico , Neutropenia/tratamento farmacológico , Guias de Prática Clínica como Assunto/normas , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Europa (Continente)/epidemiologia , Febre/epidemiologia , Febre/microbiologia , Humanos , Leucemia/epidemiologia , Leucemia/microbiologia , Neutropenia/epidemiologia , Neutropenia/microbiologia
13.
Haematologica ; 98(12): 1836-47, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24323984

RESUMO

The detection of multi-resistant bacterial pathogens, particularly those to carbapenemases, in leukemic and stem cell transplant patients forces the use of old or non-conventional agents as the only remaining treatment options. These include colistin/polymyxin B, tigecycline, fosfomycin and various anti-gram-positive agents. Data on the use of these agents in leukemic patients are scanty, with only linezolid subjected to formal trials. The Expert Group of the 4(th) European Conference on Infections in Leukemia has developed guidelines for their use in these patient populations. Targeted therapy should be based on (i) in vitro susceptibility data, (ii) knowledge of the best treatment option against the particular species or phenotype of bacteria, (iii) pharmacokinetic/pharmacodynamic data, and (iv) careful assessment of the risk-benefit balance. For infections due to resistant Gram-negative bacteria, these agents should be preferably used in combination with other agents that remain active in vitro, because of suboptimal efficacy (e.g., tigecycline) and the risk of emergent resistance (e.g., fosfomycin). The paucity of new antibacterial drugs in the near future should lead us to limit the use of these drugs to situations where no alternative exists.


Assuntos
Antibacterianos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia/tratamento farmacológico , Guias de Prática Clínica como Assunto/normas , Farmacorresistência Bacteriana Múltipla/fisiologia , Europa (Continente)/epidemiologia , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Leucemia/epidemiologia , Leucemia/microbiologia
14.
Aust Fam Physician ; 42(11): 811-5, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24217105

RESUMO

BACKGROUND: The 2009/A/H1N1 influenza vaccination campaign was managed mainly by general practitioners (GPs); however, little is known about the challenges GPs encountered during the vaccination campaign. AIM: To analyse the challenges GPs encountered during the 2009/A/H1N1 vaccination campaign. METHODS: In-depth, semi-structured qualitative interviews were conducted with GPs in Australia, Israel and England, and subjected to thematic analysis. RESULTS: GPs experienced different levels of autonomy when organising vaccinations in clinics. Their significant role was the provision of advice about the vaccine to the patients. This role was challenged by the necessity to provide the advice as a response to the anti-vaccination messages in the media and because GPs harboured doubts about mass vaccination policies. DISCUSSION: It is important that GPs accept the rationale behind vaccination campaigns and should be given accurate information about the vaccine before the campaign commences. Trustful, two-way channels for communication between GPs and public health authorities should also be established.


Assuntos
Surtos de Doenças/prevenção & controle , Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas contra Influenza/administração & dosagem , Influenza Humana/prevenção & controle , Saúde Pública , Pesquisa Qualitativa , Vacinação/métodos , Adulto , Idoso , Austrália/epidemiologia , Inglaterra/epidemiologia , Feminino , Clínicos Gerais , Humanos , Incidência , Influenza Humana/epidemiologia , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
15.
Aust Health Rev ; 37(3): 291-9, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23731961

RESUMO

BACKGROUND: During the influenza pandemic 2009/A/H1N1, the main burden of managing patients fell on primary care physicians (PCP). This provided an excellent opportunity to investigate the implications of pandemic policies for the PCP role. AIM: To examine policies affecting the role of PCP in the pandemic response in Australia (in the state of Victoria), Israel and England. METHODS: Content analysis of the documents published by the health authorities in Australia, Israel and England during the pandemic 2009/A/H1N1. RESULTS: The involvement of PCP in the pandemic response differed among the countries in timing and allocated responsibilities. The Israeli approach during the containment phase was to maximise the protection of PCP at the expense of putting pressure on hospitals where the suspected cases were tested and treated. In Australia and England, PCP managed the suspected patients from the beginning of the pandemic. The work of PCP in England was supported by the introduction of the National Pandemic Flu Service during the mitigation phase, whereas Australian PCP had no additional support structures and their role was constant and intensive throughout the pandemic period. CONCLUSION: Health authorities need to engage with representatives of PCP to evaluate policies for pandemic planning and management. Adequate support and protection for PCP during different stages of pandemic management should be provided. What is known about the topic? During the influenza pandemic 2009/A/H1N1, the main burden of diagnosing and managing the patients fell on PCP. The prominent role of PCP in the 2009/A/H1N1 pandemic presents an excellent opportunity to investigate implications of pandemic policies for primary care and to tackle the possible problems that these policies may impose on the ability of PCP to effectively participate in the public health response. What does this paper add? This paper examines policies that affected the roles of PCP in managing the influenza pandemic 2009/A/H1N1 in three countries: Australia, Israel and England. Although general evaluations of the pandemic response in different countries have previously been reported, this is the first study that focuses on policies for pandemic management at the primary care level. What are the implications for practitioners? Practitioners (PCP and primary care workers in general) would benefit if pandemic preparedness plans were constructed to provide an adequate system of support and protection to primary care workers during different stages of pandemic management. For policy makers, this analysis may help to overhaul the strategies for primary care engagement in the pandemic response.


Assuntos
Política de Saúde , Influenza Humana/epidemiologia , Pandemias/prevenção & controle , Atenção Primária à Saúde/normas , Austrália , Bibliometria , Comparação Transcultural , Planejamento em Desastres/métodos , Planejamento em Desastres/normas , Inglaterra , Humanos , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/diagnóstico , Influenza Humana/terapia , Israel , Pessoa de Meia-Idade , Atenção Primária à Saúde/métodos , Vitória
16.
PLoS One ; 17(4): e0267140, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35436301

RESUMO

BACKGROUND: The ability to accurately distinguish bacterial from viral infection would help clinicians better target antimicrobial therapy during suspected lower respiratory tract infections (LRTI). Although technological developments make it feasible to rapidly generate patient-specific microbiota profiles, evidence is required to show the clinical value of using microbiota data for infection diagnosis. In this study, we investigated whether adding nasal cavity microbiota profiles to readily available clinical information could improve machine learning classifiers to distinguish bacterial from viral infection in patients with LRTI. RESULTS: Various multi-parametric Random Forests classifiers were evaluated on the clinical and microbiota data of 293 LRTI patients for their prediction accuracies to differentiate bacterial from viral infection. The most predictive variable was C-reactive protein (CRP). We observed a marginal prediction improvement when 7 most prevalent nasal microbiota genera were added to the CRP model. In contrast, adding three clinical variables, absolute neutrophil count, consolidation on X-ray, and age group to the CRP model significantly improved the prediction. The best model correctly predicted 85% of the 'bacterial' patients and 82% of the 'viral' patients using 13 clinical and 3 nasal cavity microbiota genera (Staphylococcus, Moraxella, and Streptococcus). CONCLUSIONS: We developed high-accuracy multi-parametric machine learning classifiers to differentiate bacterial from viral infections in LRTI patients of various ages. We demonstrated the predictive value of four easy-to-collect clinical variables which facilitate personalized and accurate clinical decision-making. We observed that nasal cavity microbiota correlate with the clinical variables and thus may not add significant value to diagnostic algorithms that aim to differentiate bacterial from viral infections.


Assuntos
Infecções Bacterianas , Microbiota , Infecções Respiratórias , Viroses , Infecções Bacterianas/tratamento farmacológico , Proteína C-Reativa/metabolismo , Humanos , Nariz/microbiologia , Infecções Respiratórias/tratamento farmacológico , Viroses/diagnóstico
18.
Emerg Infect Dis ; 17(9): 1740-3, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21888809

RESUMO

During the pandemic (H1N1) 2009 outbreak in Israel, incidence rates among children were 2× higher than that of the previous 4 influenza seasons; hospitalization rates were 5× higher. Children hospitalized for pandemic (H1N1) 2009 were older and had more underlying chronic diseases than those hospitalized for seasonal influenza.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Influenza Humana/epidemiologia , Pandemias , Adolescente , Criança , Pré-Escolar , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Lactente , Influenza Humana/virologia , Israel/epidemiologia , Fatores de Risco , Estações do Ano , Estatísticas não Paramétricas
19.
Haematologica ; 96(8): 1231-5, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21546495

RESUMO

During 2009, a new strain of A/H1N1 influenza appeared and became pandemic. A prospective study was performed to collect data regarding risk factors and outcome of A/H1N1 in hematopoietic stem cell transplant recipients. Only verified pandemic A/H1N1 influenza strains were included: 286 patients were reported, 222 allogeneic and 64 autologous recipients. The median age was 38.3 years and the median time from transplant was 19.4 months. Oseltamivir was administered to 267 patients and 15 patients received zanamivir. One hundred and twenty-five patients (43.7%) were hospitalized. Ninety-three patients (32.5%) developed lower respiratory tract disease. In multivariate analysis, risk factors were age (OR 1.025; 1.01-1.04; P=0.002) and lymphopenia (OR 2.49; 1.33-4.67; P<0.001). Thirty-three patients (11.5%) required mechanical ventilation. Eighteen patients (6.3%) died from A/H1N1 infection or its complications. Neutropenia (P=0.03) and patient age (P=0.04) were significant risk factors for death. The 2009 A/H1N1 influenza pandemic caused severe complications in stem cell transplant recipients.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/epidemiologia , Pandemias , Adolescente , Adulto , Idoso , Antivirais/uso terapêutico , Criança , Pré-Escolar , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Influenza Humana/complicações , Influenza Humana/mortalidade , Linfopenia/complicações , Pessoa de Meia-Idade , Oseltamivir/uso terapêutico , Pneumonia/complicações , Fatores de Risco , Resultado do Tratamento , Vacinação , Adulto Jovem
20.
Pediatr Blood Cancer ; 57(4): 681-3, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21618408

RESUMO

We report a successful umbilical cord blood transplantation (UCBT) in an 8-month male with Wiskott-Aldrich syndrome (WAS) and congenital cytomegalovirus (CMV) infection. The child presented at 3 months of age with symptomatic thrombocytopenia and CMV infection. Despite appropriate antiviral treatment no rise in the platelet count was observed. Genetic analysis confirmed the diagnosis of WAS. The clinical course was complicated by severe CMV retinitis with bilateral retinal hemorrhages and renal vasculitis. He underwent unrelated UCBT resulting in a rapid resolution of autoimmunity and thrombocytopenia.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/cirurgia , Síndrome de Wiskott-Aldrich/cirurgia , Infecções por Citomegalovirus/fisiopatologia , Humanos , Lactente , Masculino , Transplante Homólogo , Síndrome de Wiskott-Aldrich/fisiopatologia
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