The diagnostic value of nasal microbiota and clinical parameters in a multi-parametric prediction model to differentiate bacterial versus viral infections in lower respiratory tract infections.

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.

8th European Conference on Infections in Leukaemia: 2020 guidelines for the diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or post-haematopoietic cell transplantation.

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.

Intercontinental study on pre-engraftment and post-engraftment Gram-negative rods bacteremia in hematopoietic stem cell transplantation patients: Risk factors and association with mortality.

OBJECTIVES: We present here data on Gram-negative rods bacteremia (GNRB) rates, risk factors and associated mortality. METHODS: Data on GNRB episodes were prospectively collected in 65 allo-/67 auto-HSCT centers in 24 countries (Europe, Asia, Australia). In patients with and without GNRB, we compared: demography, underlying disease, HSCT-related data, center` fluoroquinolone prophylaxis (FQP) policy and accreditation status, and involvement of infection control team (ICT). RESULTS: The GNRB cumulative incidence among 2818 allo-HSCT was: pre-engraftment (pre-eng-allo-HSCT), 8.4 (95% CI 7-9%), post-engraftment (post-eng-allo-HSCT), 5.8% (95%CI: 5-7%); among 3152 auto-HSCT, pre-eng-auto-HSCT, 6.6% (95%CI: 6-7%), post-eng-auto-HSCT, 0.7% (95%CI: 0.4-1.1%). GNRB, especially MDR, was associated with increased mortality. Multivariate analysis revealed the following GNRB risk factors: (a) pre-eng-allo-HSCT: south-eastern Europe center location, underlying diseases not at complete remission, and cord blood source; (b) post-eng-allo-HSCT: center location not in northwestern Europe; underlying non-malignant disease, not providing FQP and never accredited. (c) pre-eng-auto-HSCT: older age, autoimmune and malignant (vs. plasma cell) disease, and ICT absence. CONCLUSIONS: Benefit of FQP should be explored in prospective studies. Increased GNRB risk in auto-HSCT patients transplanted for autoimmune diseases is worrying. Infection control and being accredited are possibly protective against bacteremia. GNRB are associated with increased mortality.

The molluscum contagiosum BOTE sign-Infected or inflamed?

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.

Central nervous system disorders after hematopoietic stem cell transplantation: a prospective study of the Infectious Diseases Working Party of EBMT.

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.

Pharmacokinetics and Pharmacodynamics of Conventional-Dose vs Triple-Dose Oseltamivir in Severely Immunocompromised Children With Influenza.

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.

The Clinical Presentation of Pediatric Mycoplasma pneumoniae Infections-A Single Center Cohort.

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.

Antibiotic misuse in respiratory tract infections in children and adults-a prospective, multicentre study (TAILORED Treatment).

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.

Vaccination of haemopoietic stem cell transplant recipients: guidelines of the 2017 European Conference on Infections in Leukaemia (ECIL 7).

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.

Vaccination of patients with haematological malignancies who did not have transplantations: guidelines from the 2017 European Conference on Infections in Leukaemia (ECIL 7).

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.

Staphylococcus aureus Bacteremia in Children: Antibiotic Resistance and Mortality.

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.

Antimicrobial Resistance in Gram-Negative Rods Causing Bacteremia in Hematopoietic Stem Cell Transplant Recipients: Intercontinental Prospective Study of the Infectious Diseases Working Party of the European Bone Marrow Transplantation Group.

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.

Management of Epstein-Barr Virus infections and post-transplant lymphoproliferative disorders in patients after allogeneic hematopoietic stem cell transplantation: Sixth European Conference on Infections in Leukemia (ECIL-6) guidelines.

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.

Infants under two months of age with urinary tract infections are showing increasing resistance to empirical and oral antibiotics.

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.

Preparing for imported Ebola cases in Israel, 2014 to 2015.

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.

Challenges of the Pandemic Response in Primary Care during Pre-Vaccination Period: A Qualitative Study.

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.

IMMUNODEFICIENCIES. Impairment of immunity to Candida and Mycobacterium in humans with bi-allelic RORC mutations.

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.

Infections caused by Fusobacterium in children: a 14-year single-center experience.

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.

A multifaceted 'omics' approach for addressing the challenge of antimicrobial resistance.

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.

Fourth European Conference on Infections in Leukaemia (ECIL-4): guidelines for diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or allogeneic haemopoietic stem-cell transplantation.

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.