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1.
J Neurol ; 267(2): 430-439, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31664549

RESUMO

We performed a prospective study to evaluate the types and characteristics of central nervous system (CNS) disorders in patients after hematopoietic stem cell transplantation. The study included 163 episodes of CNS disorders of which 58 (36%) were infections. Proven or probable infections were documented in 34 patients and included fungi (n = 10, 29%), viruses (n = 12, 35%), Toxoplasma spp. (n = 9, 27%) and bacteria (n = 3, 9%). Non-infectious neurological disorders (n = 105, 64%) frequently encompassed metabolic/drug-induced abnormalities (n = 28, 27%) or cerebral vascular events (n = 22, 21%). Median onset times were later for infectious (day + 101) vs non-infectious neurological disorders (day + 50, p = 0.009). An unremarkable cranial CT scan was found in 33% of infection episodes. Absence of cerebrospinal fluid pleocytosis despite a normal or increased peripheral blood white blood cell count occurred in 26% of infections. Day-30 mortality rates were significantly higher for fungal (87%) vs non-fungal infections (40%, p < 0.001). Significantly higher mortality rates were also documented for cerebral vascular events than for other non-infectious disorders (86% vs 34%, p < 0.001). Our prospective study shows that diagnostic findings in CNS infections might differ between hematopoietic stem cell transplant recipients and immunocompetent hosts. Special awareness and timely initiation of adequate diagnostics are crucial to improve the prognosis of these patients.

2.
Open Forum Infect Dis ; 6(10): ofz430, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31660381

RESUMO

This randomized phase 1b study evaluated the pharmacokinetics/pharmacodynamics of conventional-dose (30-75 mg twice daily [BID]) vs triple-dose (90-225 mg BID; weight-adjusted) oseltamivir for treatment of influenza in severely immunocompromised children <13 years. Oseltamivir carboxylate (OC) Cmax and AUC0-12h were ~2-fold higher with triple-dose vs conventional-dose oseltamivir. Increased dose/exposure of oseltamivir/OC did not improve virological outcomes or reduce viral resistance. Median time to cessation of viral shedding was similar with triple-dose and conventional-dose oseltamivir (150.7 vs 157.1 hours, respectively); median time to alleviation of baseline fever was longer with conventional-dose oseltamivir (28.4 vs 11.3 hours). No new safety signals were identified.

3.
Pediatr Infect Dis J ; 38(7): 698-705, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30985519

RESUMO

BACKGROUND: Mycoplasma pneumoniae (MP) is a major cause of community-acquired upper and lower respiratory infections in school-age children; however, there is increasing recognition that younger children are also affected. Clinical manifestations vary from asymptomatic, to severe complicated pneumonia sometimes with extrapulmonary manifestations. METHODS: We reviewed the medical records of all MP positive pediatric patients admitted to the Hadassah-Hebrew University Medical Center. MP positive case was defined if MP polymerase chain reaction was positive from an oropharyngeal swab sent from 2007 to 2017. RESULTS: During the study period, we identified 353 MP positive pediatric cases, of which 51.3% (181 of 353) were younger than 6 years old. Full clinical data were available for 332 of 353 (94%). The median age was 5.7 years (range, 3 weeks to 18 years). Disease presentation differed between younger and older children. Children older than 6 years were more likely to have chest radiograph confirmed pneumonia (66% vs. 52%; P = 0.009), while younger children were more likely to have other respiratory manifestations (37% vs. 25%; P = 0.017). The duration of hospitalization and pediatric intensive care unit admission rate, however, did not differ between age groups. The rate of extrapulmonary manifestations were also similar. CONCLUSIONS: MP-associated infection is a significant cause of hospitalization in the pediatric population including younger children (<6 years old). However, the clinical presentation in younger age is less typical than is thought. These findings should prompt clinicians to consider MP infections also in children younger than 6 admitted with fever even without pneumonia.

4.
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
5.
Lancet Infect Dis ; 19(6): e200-e212, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30744963

RESUMO

Infection is a main concern after haemopoietic stem cell transplantation (HSCT) and a major cause of transplant-related mortality. Some of these infections are preventable by vaccination. Most HSCT recipients lose their immunity to various pathogens as soon as the first months after transplant, irrespective of the pre-transplant donor or recipient vaccinations. Vaccination with inactivated vaccines is safe after transplantation and is an effective way to reinstate protection from various pathogens (eg, influenza virus and Streptococcus pneumoniae), especially for pathogens whose risk of infection is increased by the transplant procedure. The response to vaccines in patients with transplants is usually lower than that in healthy individuals of the same age during the first months or years after transplant, but it improves over time to become close to normal 2-3 years after the procedure. However, because immunogenic vaccines have been found to induce a response in a substantial proportion of the patients as early as 3 months after transplant, we recommend to start crucial vaccinations with inactivated vaccines from 3 months after transplant, irrespectively of whether the patient has or has not developed graft-versus-host disease (GvHD) or received immunosuppressants. Patients with GvHD have higher risk of infection and are likely to benefit from vaccination. Another challenge is to provide HSCT recipients the same level of vaccine protection as healthy individuals of the same age in a given country. The use of live attenuated vaccines should be limited to specific situations because of the risk of vaccine-induced disease.

6.
Lancet Infect Dis ; 19(6): e188-e199, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30744964

RESUMO

Patients with haematological malignancies are at high risk of infection because of various mechanisms of humoral and cell-mediated immune deficiencies, which mainly depend on underlying disease and specific therapies. Some of these infections are vaccine preventable. However, these malignancies are different from each other, and the treatment approaches are diverse and rapidly evolving, so it is difficult to have a common programme for vaccination in a haematology ward. Additionally, because of insufficient training about the topic, vaccination is an area often neglected by haematologists, and influenced by cultural differences, even among health-care workers, in compliance to vaccines. Several issues are encountered when addressing vaccination in haematology: the small size of the cohorts that makes it difficult to show the clinical benefits of vaccination, the subsequent need to rely on biological parameters, their clinical pertinence not being established in immunocompromised patients, scarcity of clarity on the optimal timing of vaccination in complex treatment schedules, and the scarcity of data on long-term protection in patients receiving treatments. Moreover, the risk of vaccine-induced disease with live-attenuated vaccines strongly limits their use. Here we summarise guidelines for patients without transplantations, and address the issue by the haematological group-myeloid and lymphoid-of diseases, with a special consideration for children with acute leukaemia.

7.
Pediatr Infect Dis J ; 38(5): 459-463, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30239476

RESUMO

BACKGROUND: Staphylococcus aureus (SA) is a major cause of bacteremia in children. Methicillin-resistant SA (MRSA) is considered a public health threat; however, the differences in the prognosis of children with methicillin-susceptible SA (MSSA) versus MRSA bacteremia are not well defined. METHODS: Data from all SA bacteremia events in children (0-16 years) from 2002 to 2016 in a single Israeli tertiary center were collected. Positive cultures within 48 hours of hospitalization were considered community associated (CA). Those obtained afterward or from children hospitalized within the previous year were considered health-care associated (HA). RESULTS: We recorded 427 events, 284 (66%) were HA, 64 (15%) were MRSA and 9 (2%) were CA-MRSA. There was no increase in MRSA during the study period. In-hospital, 30-day and 1-year mortality were 3% (12 cases), 3.5% (16 cases), and 12% (50 cases), respectively. A multivariable analysis controlling for demographics, admitting department and prior morbidity showed an increased 1-year mortality in children with HA bacteremia (hazard ratio [HR] 4.1; 95% confidence interval [CI]: 1.3-12) and prior chronic disease (HR 3.4; 95% CI 1.2 to 9.0). MRSA was not independently associated with increased one-year mortality compared with MSSA: HR (95% CI: 1.4 [0.6-3.1]). CONCLUSIONS: Short-term pediatric mortality after SA bacteremia is low. HA-SA bacteremia has an increased long-term risk for mortality, particularly in children with chronic diseases. Our data suggest mortality was not increased for MRSA compared with MSSA bacteremia. The very low rate of CA-MRSA bacteremia justifies the current practice not to include glycopeptides in the empiric treatment of CA bacteremia in Israel.

8.
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
9.
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
10.
Curr Drug Targets ; 2016 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-27397064

RESUMO

Neutropenic patients with malignancies and hematopoietic stem cell transplant recipients are prone to severe infections. Reversal of neutropenia with granulocyte transfusion (GTX) from donors stimulated with GCSF with/without steroids aims to improve outcome of infection. Cochrane analysis of randomized controlled studies, however, failed to show reduced mortality following GTX in conjunction with antibiotics. Non-randomized studies published during the last 20 years produced a very broad spectrum of results. The most important factors predicting favorable response to GTX are high number of granulocytes transfused and recovery from neutropenia. The response in patients with bad performance status, septic shock, multiple co-morbidities, multi-organ dysfunction and those in intensive care was poor. The response in fungal infections is generally worse than in bacterial infections. Cochrane analysis of prospective GTX clinical trials in preventing infection also failed to show reduced overall mortality. Adverse reactions in recipients are usually mild, although severe reactions, including respiratory deterioration, have been observed. Based on current evidence, GTX, at the amount at least 1x1010 per dose, can be considered in certain patients with severe neutropenia or congenital disorder of neutrophil function with proven or highly probable fungal or bacterial infection unresponsive to appropriate antimicrobial therapy with expected duration of neutropenia for at least 5 days; in cases where neutrophil recovery is anticipated.

11.
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
12.
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
13.
Artigo em Inglês | MEDLINE | ID: mdl-26473026

RESUMO

BACKGROUND: During the 2009/A/H1N1 pandemic, the main burden of the patient management fell on primary care physicians (PCPs), and they were the principal implementers of pandemic policies. Broad involvement of PCPs in the pandemic response offered an excellent opportunity to investigate the challenges that they encountered. OBJECTIVE: To examine challenges faced by PCPs as they implemented pandemic policies in Australia, Israel and England before the 2009/A/H1N1 pandemic vaccine became available. METHODS: This is a qualitative descriptive study that employed in-depth semi-structured interviews with 65 PCPs from Australia, Israel and England. The data were analysed thematically to provide a detailed account of the themes. RESULTS: Challenges in three fields of the pandemic response were identified. (i) Consultation of patients was challenged by the high flow of patients, sick and worried-well, the necessity to provide personalised information about the disease during consultations, and unfamiliar antiviral treatment. (ii) Performance of public health responsibilities was complicated in regards to patient segregation and introduction of personal protection measures. (iii) Communication with the health authorities was inefficient, with no established route to provide feedback about the pandemic policies. CONCLUSIONS: The experience of the 2009/A/H1N1 pandemic highlighted the centrality of primary care in the pandemic response. Despite intensive pre-pandemic planning, numerous barriers for implementation of the pandemic policies in primary care were identified. Investigation of three different approaches for involvement of PCPs in the pandemic management showed that none of these approaches worked smoothly.

14.
Science ; 349(6248): 606-613, 2015 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-26160376

RESUMO

Human inborn errors of immunity mediated by the cytokines interleukin-17A and interleukin-17F (IL-17A/F) underlie mucocutaneous candidiasis, whereas inborn errors of interferon-γ (IFN-γ) immunity underlie mycobacterial disease. We report the discovery of bi-allelic RORC loss-of-function mutations in seven individuals from three kindreds of different ethnic origins with both candidiasis and mycobacteriosis. The lack of functional RORγ and RORγT isoforms resulted in the absence of IL-17A/F-producing T cells in these individuals, probably accounting for their chronic candidiasis. Unexpectedly, leukocytes from RORγ- and RORγT-deficient individuals also displayed an impaired IFN-γ response to Mycobacterium. This principally reflected profoundly defective IFN-γ production by circulating γδ T cells and CD4(+)CCR6(+)CXCR3(+) αß T cells. In humans, both mucocutaneous immunity to Candida and systemic immunity to Mycobacterium require RORγ, RORγT, or both.


Assuntos
Candida albicans/imunologia , Candidíase Mucocutânea Crônica/genética , Imunidade/genética , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Imunodeficiência Combinada Severa/genética , Tuberculose Bovina/genética , Tuberculose Pulmonar/genética , Alelos , Animais , Candidíase Mucocutânea Crônica/complicações , Candidíase Mucocutânea Crônica/imunologia , Bovinos , Criança , Pré-Escolar , Análise Mutacional de DNA , Exoma/genética , Feminino , Rearranjo Gênico da Cadeia alfa dos Receptores de Antígenos dos Linfócitos T , Humanos , Interferon gama/imunologia , Interleucina-17/imunologia , Camundongos , Mutação , Mycobacterium bovis/imunologia , Mycobacterium bovis/isolamento & purificação , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/isolamento & purificação , Linhagem , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/genética , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Linfócitos T/imunologia , Timo/anormalidades , Timo/imunologia , Tuberculose Bovina/imunologia , Tuberculose Pulmonar/imunologia
15.
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
16.
Future Microbiol ; 10(3): 365-76, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25812460

RESUMO

The inappropriate use of antibiotics has severe global health and economic consequences, including the emergence of antibiotic-resistant bacteria. A major driver of antibiotic misuse is the inability to accurately distinguish between bacterial and viral infections based on currently available diagnostic solutions. A multifaceted 'omics' approach that integrates personalized patient data such as genetic predisposition to infections (genomics), natural microbiota composition and immune response to infection (proteomics and transcriptomics) together with comprehensive pathogen profiling has the potential to help physicians improve their antimicrobial prescribing practices. In this respect, the EU has funded a multidisciplinary project (TAILORED-Treatment) that will develop novel omics-based personalized treatment schemes that have the potential to reduce antibiotic consumption, and help limiting the spread of antibiotic resistance.


Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/tratamento farmacológico , Farmacorresistência Bacteriana , Genômica , Proteômica , Antibacterianos/uso terapêutico , Bactérias/isolamento & purificação , Infecções Bacterianas/microbiologia , Biologia Computacional , Diagnóstico Diferencial , Uso de Medicamentos , Humanos , Microbiota , Medicina de Precisão/métodos , Viroses/diagnóstico
17.
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
18.
Pediatr Infect Dis J ; 33(6): 571-5, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24836755

RESUMO

BACKGROUND: Urinary tract infection (UTI) is the most frequent severe bacterial infection in infants. Up to 31% of infants with UTI have bacteremia. METHODS: We retrospectively identified all infants aged 0-2 months who were managed in our hospital with UTI during a 1-year period. Those with bacteremia were compared with those without bacteremia, according to the following variables: ethnicity, age, gender, white blood cell and polymorphonuclear counts, C-reactive protein, urinalysis and blood creatinine values as related to age-appropriate norms, imaging and outcome. RESULTS: We identified 81 infants with 82 episodes of UTI. Most occurred in males (72.8%) and 35 (42.7%) were in infants of non-Jewish origin. In 14/81 (17.3%) of episodes, Escherichia coli was cultured from blood. In multivariate analysis, increased blood creatinine levels (P = 0.004) and non-Jewish origin (P = 0.006) were associated with bacteremia. Time to defervescence was significantly longer in bacteremic versus nonbacteremic children (P = 0.018). Duration of hospitalization was longer in bacteremic infants-10 (7-17) days in bacteremic versus 7 (1-14) days in nonbacteremic children (P < 0.001). CONCLUSIONS: In infants aged 0-2 months with UTI, increased blood creatinine value at admission was associated with bacteremia. This value provides an additional clue on admission, independent of personal judgment, to help identify infants at higher risk for bacteremia, prolonged hospitalization and possible complications.


Assuntos
Bacteriemia/epidemiologia , Infecções Urinárias/epidemiologia , Infecções Urinárias/microbiologia , Feminino , Humanos , Lactente , Recém-Nascido , Israel/epidemiologia , Judeus , Masculino , Estudos Retrospectivos
19.
Semin Arthritis Rheum ; 43(4): 508-12, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24012046

RESUMO

OBJECTIVES: Systemic lupus erythematosus (SLE) occurs more commonly in females than in males. Recent evidence suggests that genetic factors transmitted by the X-chromosome may confer increased risk for autoimmune disease in general, and for SLE in particular. It is therefore possible that X-chromosome polysomy might confer further increased risk for lupus. In addition to describing the clinical and immunologic features of a young woman with polysomy-X and SLE, we sought to review all other published cases associating female or male polysomy-X with SLE or other forms of autoimmunity. METHODS: We report a case of a prepubertal girl with polysomy-X and SLE. We performed a systemic literature review for cases of polysomy-X and SLE and summarize previously published cases. In addition, we reviewed reports concerning the possible association between SLE and other connective tissue diseases and male polysomy-X. RESULTS: An 11-year-old girl with tetrasomy-X (48 XXXX karyotype) presented with prolonged fever. Workup led to the diagnosis of SLE, and subsequent renal biopsy revealed mild diffuse mesangial proliferative glomerulonephritis. Two additional cases of SLE in women with 47 XXX and one of 48 XXXX karyotype were found in a literature review and compared to the present case. We identified studies that found X-chromosome polysomy to be over-represented in male patients with SLE and case descriptions of connective tissue diseases occurring in patients with polysomy-X. CONCLUSION: No consistent pattern of disease was observed in female polysomy patients with SLE. Taken together with the data concerning the frequency of polysomy-X among males with SLE, our findings provide additional support for the hypothesis that X-chromosome polysomy may confer increased susceptibility to SLE. Molecular mechanisms that might account for this phenomenon are discussed.


Assuntos
Anormalidades Craniofaciais/complicações , Deficiência Intelectual/complicações , Lúpus Eritematoso Sistêmico/complicações , Criança , Feminino , Humanos , Aberrações dos Cromossomos Sexuais
20.
Pediatr Pulmonol ; 49(10): 943-51, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24166798

RESUMO

OBJECTIVE: Assessment of asthma control in children by physicians, patients and their parents was compared, assuming parents may underestimate symptoms in asthmatic children and exploring whether physicians tend to agree with them. DESIGN: Asthma control perception was assessed in 4- to 11-year-old asthmatic children and their parents, using C-ACT, during 2011-2012. Pediatric pulmonologists used GINA guidelines for their assessment; pediatricians, not having spirometry, used the information given in addition to physical examination. The C-ACT scores given by the children and their parents were further analyzed separately, and compared with their physicians' assessment. Statistical methods, which also measured possible influence of different variables, included kappa, Chi-square, linear-by-linear association, McNemar test and logistic regression. PATIENT SELECTION: The study comprised 354 parents and children aged 4-11 years with moderate-severe asthma; 129 (36.4%) were treated by 23 pediatricians; 225 (63.6%) by 11 pediatric pulmonologists. RESULTS: The C-ACT was generally found valid in assessing asthma control (P < 0.001; κ 0.529; CI 0.441, 0.617) and showed that in 229/354 (53%) of children the asthma was uncontrolled. Nevertheless, of the 229 children who indicated their asthma was uncontrolled, 124 (54.1%) of their parents (κ 0.245; CI 0.15, 0.34) and 96 (41.9%) of their physicians believed it to be controlled (κ 0.331; 0.24, 0.43). Comparing the physician-child discordance vis-à-vis the parents, the significant difference was when 96/229 children (41.9%) and 34/126 parents (27.0%) indicated the asthma was uncontrolled while the physician determined it controlled (OR 1.95; 1.19, 3.24). There were no significant differences between pediatric pulmonologists and pediatricians. CONCLUSIONS: In addition to increasing awareness of parents to symptoms in their asthmatic children, physicians should question the child appropriately, as well as using the children's responses to C-ACT as an information source for properly assessing asthma control.


Assuntos
Asma/terapia , Atitude Frente a Saúde , Pais , Médicos , Autorrelato , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Exame Físico , Inquéritos e Questionários
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