Suchergebnisse

The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situation. ; SAM-COVID was funded by Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (COV20/01031) co-funded by European Union (ERDF/ESF, "Investing in your future") and Fundación SEIMC/GeSIDA. In addition, Juan Berenguer, Jesús ...

[Introduction] Patients with negative blood cultures (BCx) represent 85%–90% of all patients with BCx taken during hospital admission. This population usually includes a heterogeneous group of patients admitted with infectious diseases or febrile syndromes that require a blood culture. There is very little evidence of the clinical characteristics and antibiotic treatment given to these patients. ; [Methods and analysis] In a preliminary exploratory prospective cohort study of patients with BCx taken, the clinical/therapeutic characteristics and outcomes/antimicrobial stewardship opportunities of a population of patients with negative BCx will be analysed. In the second phase, using a cluster randomised crossover design, the implementation of an antimicrobial stewardship intervention targeting patients with negative BCx will be evaluated in terms of quality of antimicrobial use (duration and de-escalation), length of hospital stay and mortality. ; [Ethics and dissemination] This study has been and registered with clinicaltrials.gov. The findings of our study may support the implementation in clinical practice of an antimicrobial stewardship intervention to optimise the use of antibiotics in patients with negative BCx. The results of this study will be published in peer-reviewed journals and disseminated at national and international conferences. ; Trial registration number NCT03535324. ; This work is being supported by the Spanish Clinical Research and Clinical Trials Platform, SCReN (Spanish Clinical Research Network), funded by the ISCIII-General Subdirectorate for Evaluation and Promotion of Research, through project PT17/0017/0012) integrated in the State R & D Plan 2013-2016 and co-financed by and the European Regional Development Fund (FEDER). In addition, is being supported by the Project "PI17/01809", funded by Instituto de Salud Carlos III, integrated in the national I+D+i Plan 2017-2020 and co-funded by European Union (ERDF/ESF, "Investing in your future"). ; Peer reviewed

[Introduction] Improving our understanding of outbreaks due to antibiotic-resistant bacteria (ARB) and their control is critical in the current public health scenario. The threat of outbreaks due to ARB requires multifaceted efforts. However, a global overview of epidemiological characteristics of outbreaks due to ARB and effective infection control measures is missing. In this paper, we describe the protocol of a systematic review aimed at mapping and characterising the epidemiological aspects of outbreaks due to ARB and infection control measures in European countries. ; [Methods and analysis] The databases MEDLINE, Web of Knowledge and Cochrane library will be searched using a 3-step search strategy. Selection of articles for inclusion will be performed by 2 reviewers using predefined eligibility criteria. All study designs will be included if they report an outbreak and define the microbiological methods used for microorganism identification. The target bacteria will be methicillin-resistant and vancomycin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, ceftazidime-resistant and carbapenem-resistant Acinetobacter baumannii, ceftazidime-resistant and carbapenem-resistant Pseudomonas aeruginosa, ciprofloxacin-resistant Escherichia coli, extended-spectrum β-lactamase-producing E. coli and Klebsiella pneumoniae, carbapenem-resistant and carbapenamase-producing Enterobacteriaceae. Data will be extracted using a tailored pilot tested form and the quality of reporting will be assessed using the ORION (Outbreak Reports and Intervention Studies Of Nosocomial infections) tool. Data will be synthesised and reported by the type of ARB, setting and country. Infection control measures and bundles of measures will be described. The effectiveness will be reported as defined by the authors. Regression analysis will be used to define independent factors associated with outbreaks' control. Heterogeneity between studies will be assessed by forest plots and I² statistics. ; [Ethics and dissemination] Ethical approval is not applicable for this study. Findings will be disseminated through journal publication and conference presentations and talks. ; This research project receives support from the Innovative Medicines Initiative Joint Undertaking (IMI JU) under grant agreement numbers 115737 (COMBACTE-MAGNET) and 115618 (DRIVE-AB), resources of which are composed of financial contribution from the European Union Seventh Framework Programme (FP7/2007-2013) and EFPIA companies in kind contribution. In addition as a special form of the IMI JU grant, FS received a direct financial contribution from AstraZeneca. ; Peer reviewed

For the COMBACTE-MAGNET-EPI-Net Consortium. In Press. ; [Objectives] In 2017 the WHO published a global priority list of 12 antibiotic-resistant bacteria (ARB) in urgent need of new antibiotics. We aimed to identify and assess publicly accessible mandatory surveillance systems and outbreaks reporting for these pathogens in the 28 European Union and four European Free Trade Association member states. [Methods] Compulsory reporting was mapped by reviewing national documents without applying language restrictions and through expert consultation. Information on surveillance targets, indicators, metrics and dissemination modalities was extracted and a qualitative assessment was performed for open access systems only. [Results] Twenty-one countries (66%) had a mandate to survey at least one among the 12 WHO priority pathogens; 15 provided access to surveillance frameworks. These systems covered most frequently carbapenem-resistant Enterobacteriales (12; 38%), methicillin-resistant Staphylococcus aureus (12; 38%), and vancomycin-resistant enterococci (8; 25%). None of the European countries required reporting of resistance in Salmonella, Campylobacter, Helicobacter pylori and Neisseria gonorrhoeae. High heterogeneity was observed in data collection, reporting and dissemination among countries with clinical outcomes and risk factors being reported in less than half (22% and 25%). Only six countries (19%) implemented mandatory surveillance of outbreaks due to at least one WHO priority pathogen. [Conclusions] Our review shows that despite the increasing burden of ARB on the European population, very few countries implemented mandatory surveillance and outbreak reporting of the WHO priority pathogens. International efforts are needed to define the effectiveness of implementing mandatory reporting of these pathogens and to assess their role in reducing the spread of ARB in health-care and community settings. ; This research project receives support from the Innovative Medicines Initiative Joint Undertaking under grant agreement numbers 115737 (COMBACTE-MAGNET), resources of which are composed of financial contributions from the European Union Seventh Framework Programme (FP7/2007-2013) and EFPIA companies in kind contribution.

EUCIC StopNegative group ; [Objective]: The main objective of the study was to investigate major differences among European countries in implementing infection prevention and control (IPC) measures and reasons for reduced compliance. ; [Design]: An online survey including experts in IPC and a gap analysis were conducted to identify major limitations in implementing IPC guidelines. ; [Setting]: Europe. ; [Main outcome measures]: Four areas were targeted: (1) healthcare structure, (2) finances, (3) culture and (4) education and awareness. Perceived compliance to IPC measures was classified as low (80%). Countries were classified in three regions: North-Western Europe (NWE), Eastern Europe (EE) and Southern Europe (SE). ; [Results]: In total, 482 respondents from 34 out of 44 (77.3%) European countries participated. Respondents reported availability of national guidelines to control multidrug-resistant Gram-negatives (MDR-GN) in 20 countries (58.0%). According to participants, compliance with IPC measures ranged from 17.8% (screening at discharge) to 96.0% (contact precautions). Overall, three areas were identified as critical for the compliance rate: (1) number of infection control staff, (2) IPC dedicated educational programmes and (3) number of clinical staff. Analysis of reasons for low compliance showed high heterogeneity among countries: participants from NWE and SE deemed the lack of educational programmes as the most important, while those from EE considered structural reasons, such as insufficient single bed rooms or lacking materials for isolation, as main contributors to the low compliance. ; [Conclusions]: Although national guidelines to reduce the spread of MDR-GN are reported in the majority of the European countries, low compliance with IPC measures was commonly reported. Reasons for the low compliance are multifactorial and vary from region to region. Cross-country actions to reduce the spread of MDR-GN have to consider structural and cultural differences in countries. Locally calibrated interventions may be fruitful in the future. ; The study was partly funded (NTM) by a grant by the Baden-Württemberg Ministry of Science, Research and the Arts (MWK; grant: "Surveillance von Mehrfach-Antibiotika-Resistenzen"). The study was furthermore non-financially supported by ESCMIDs European Committee on Infection Control. The open-access fee was covered by ESCMID. ; Peer reviewed

[Introduction] Despite the increasing importance of infections due to multidrug-resistant organisms (MDROs), there is a lack of comprehensive information about the burden of disease and outcomes of key infections caused by these pathogens. The aim of the ABOUT-MDRO (A systematic review on the burden and outcomes of infections due to multidrug resitant organisms) project is to provide estimations of the burden of some key infections and their outcomes caused by the target MDROs. ; [Methods and analysis] A systematic literature search will be performed using MEDLINE/PubMed, Elsevier's SCOPUS, Cochrane library, Clinical trials and Web of Science, as well as the Surveillance Systems from Public Health Institutions and Scientific Societies for Antimicrobial Resistance and Healthcare-Associated Infections in Europe database of European surveillance systems, for data on prevalence/incidence, mortality and length of stay of target infections in hospitalised patients (including ventilator-associated pneumonia, hospital-acquired pneumonia, complicated intra-abdominal infections, complicated urinary tract infections, skin and soft tissue infections and bloodstream infections) and in specific populations (children, hospital wards, neutropenic patients) caused by cephalosporin-resistant or carbapenem-resistant Enterobacteriaceae, carbapenem-resistant Pseudomonas aeruginosa and Acinetobacter spp., methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus spp. The information retrieved will be tabulated and pooled estimates and 95% CIs calculated of rates and outcomes, using random effects models. Relationships between rates and outcomes in randomised control trials and epidemiological studies, and data of proportions and incidence/prevalence rates will also be analysed. The information collected in this study will be useful for identifying gaps in our knowledge in terms of incidence/prevalence and clinical outcomes of infections caused by MDROs, and for informing priorities in infection control and the research and design of appropriate studies. ; [Ethics and dissemination] This study will be based on published data so we did not require ethical approval. Formal consent is not required. The results of this review will be reported according to the Preferred Reporting Items for Systematic Review and Meta-Analyses statement. Data will be presented at international conferences and published in peer-reviewed journals. ; [Registration details] PROSPERO (https://www.crd.york.ac.uk/prospero/) (CRD42019124185). ; The ABOUT-MDRO Study is part of the COMBACTE-MAGNET project (Combatting Bacterial Resistance in Europe - Molecules against Gram-negative Infections), Innovative Medicines Initiative (IMI), European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies' in-kind contribution, Grant agreement 115737. ZRP-B and JR-B received funding for research from Plan Nacional de I+D+i 2013‐2016 and the Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0001), co-financed by the European Development Regional Fund 'A way to achieve Europe', Operative Programme Intelligent Growth 2014‐2020.

EPI-NET group. ; [Introduction] The worldwide spread of antimicrobial resistance is now recognised as a global public health threat. Owing to the geographical heterogeneity, complexity and continuously evolving dynamics of resistant organisms and genes, surveillance is a key tool for understanding, measuring and informing actions in the fight against this problem. To date there is no harmonisation of key indicators or of methodologies used to obtain them. ; [Methods and analysis] The main objective of this project is to systematically review and analyse the current publicly available surveillance activities on antimicrobial resistance and healthcare-associated infections in Europe. Eligible activities are those endorsed by regional, national or transnational health organisations and scientific societies providing data on a periodic basis. Grey and peer-reviewed literature will be searched with no language restrictions. Three independent reviewers will perform a two-step selection process using a previously piloted, tailored electronic data extraction form. Descriptive summaries and tables of all relevant findings will be performed and reported according to PRISMA guidelines. ; [Ethics and dissemination] We did not seek ethical approval for this study because the data to be collected are not linked to individuals. Data will be presented at international conferences and published in peer-reviewed journals. ; [Trial registration number] CRD42016033867. ; This research project receives support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115737 resources of which are composed of financial contribution from the European Union Seventh Framework Programme (FP7/2007/2013) and EFPIA companies in kind contribution. JRB also received funding for research from Ministerio de Economía y Competitividad, Instituto de Salud Carlos III—cofinanced by European Development Regional Fund 'A way to achieve Europe' ERDF, Spanish Network for the Research in Infectious Diseases (REIPI RD12/0015). ; Peer reviewed

COVID-19 is a major worldwide health problem because of acute respiratory distress syndrome, and mortality. Several lines of evidence have suggested a relationship between the vitamin D endocrine system and severity of COVID-19. We present a survival study on a retrospective cohort of 15,968 patients, comprising all COVID-19 patients hospitalized in Andalusia between January and November 2020. Based on a central registry of electronic health records (the Andalusian Population Health Database, BPS), prescription of vitamin D or its metabolites within 15–30 days before hospitalization were recorded. The effect of prescription of vitamin D (metabolites) for other indication previous to the hospitalization was studied with respect to patient survival. Kaplan–Meier survival curves and hazard ratios support an association between prescription of these metabolites and patient survival. Such association was stronger for calcifediol (Hazard Ratio, HR = 0.67, with 95% confidence interval, CI, of [0.50–0.91]) than for cholecalciferol (HR = 0.75, with 95% CI of [0.61–0.91]), when prescribed 15 days prior hospitalization. Although the relation is maintained, there is a general decrease of this effect when a longer period of 30 days prior hospitalization is considered (calcifediol HR = 0.73, with 95% CI [0.57–0.95] and cholecalciferol HR = 0.88, with 95% CI [0.75, 1.03]), suggesting that association was stronger when the prescription was closer to the hospitalization. ; This work is supported by grants PID2020-117979RB-I00 from the Spanish Ministry of Science and Innovation, IMP/0019, ACCI2018/29 from CIBERER-ISCIII; COV20/00788 from the Instituto de Salud Carlos III (ISCIII), co-funded with European Regional Development Funds (ERDF); grant G999088Q from the Fundación BBVA; grant H2020 Programme of the European Union grants Marie Curie Innovative Training Network "Machine Learning Frontiers in Precision Medicine" (MLFPM) (GA 813533); P18-RT-3471 from Consejería de Salud y Familias de la Junta de Andalucía; CB16/10/00245, ...

The COVID-19 pandemic represents an unprecedented opportunity to exploit the advantages of personalized medicine for the prevention, diagnosis, treatment, surveillance and management of a new challenge in public health. COVID-19 infection is highly variable, ranging from asymptomatic infections to severe, life-threatening manifestations. Personalized medicine can play a key role in elucidating individual susceptibility to the infection as well as inter-individual variability in clinical course, prognosis and response to treatment. Integrating personalized medicine into clinical practice can also transform health care by enabling the design of preventive and therapeutic strategies tailored to individual profiles, improving the detection of outbreaks or defining transmission patterns at an increasingly local level. SARS-CoV2 genome sequencing, together with the assessment of specific patient genetic variants, will support clinical decision-makers and ultimately better ways to fight this disease. Additionally, it would facilitate a better stratification and selection of patients for clinical trials, thus increasing the likelihood of obtaining positive results. Lastly, defining a national strategy to implement in clinical practice all available tools of personalized medicine in COVID-19 could be challenging but linked to a positive transformation of the health care system. In this review, we provide an update of the achievements, promises, and challenges of personalized medicine in the fight against COVID-19 from susceptibility to natural history and response to therapy, as well as from surveillance to control measures and vaccination. We also discuss strategies to facilitate the adoption of this new paradigm for medical and public health measures during and after the pandemic in health care systems. ; The authors included in this review have received funding for two COVID-19 projects (COVID GWAs, Premed COVID-19) from the Consejería de Salud y Familias of the Andalusian Government. DMM's contract is supported by the Andalussian government (Proyectos Estratégicos Fondos Feder PE-0451-2018). ; Peer reviewed

[Introduction] Within the context of antimicrobial stewardship programmes, de-escalation of antimicrobial therapy is one of the proposed strategies for reducing the unnecessary use of broad-spectrum antibiotics (BSA). The empirical treatment of nosocomial and some healthcare-associated bloodstream infections (BSI) frequently includes a beta-lactam with antipseudomonal activity as monotherapy or in combination with other drugs, so there is a great opportunity to optimise the empirical therapy based on microbiological data. De-escalation is assumed as standard of care for experts in infectious diseases. However, it is less frequent than it would desirable. ; [Methods and analysis] The SIMPLIFY trial is a multicentre, open-label, non-inferiority phase III randomised controlled clinical trial, designed as a pragmatic 'real-practice' trial. The aim of this trial is to demonstrate the non-inferiority of de-escalation from an empirical beta-lactam with antipseudomonal activity to a targeted narrow-spectrum antimicrobial in patients with BSI due to Enterobacteriaceae. The primary outcome is clinical cure, which will be assessed at the test of cure visit. It will be conducted at 19 Spanish public and university hospitals. ; [Ethics and dissemination] Each participating centre has obtained the approval of the ethics review committee, the agreement of the directors of the institutions and authorisation from the Spanish Regulatory Agency (Agencia Española del Medicamento y Productos Sanitarios). Data will be presented at international conferences and published in peer-reviewed journals. ; [Discussion] Strategies to reduce the use of BSA should be a priority. Most of the studies that support de-escalation are observational, retrospective and heterogeneous. A recent Cochrane review stated that well-designed clinical trials should be conducted to assess the safety and efficacy of de-escalation. ; [Trial registration number] The European Union Clinical Trials Register: EudraCT number 2015-004219-19. Clinical trials.gov: NCT02795949. Protocol version: V.2.0, dated 16 May 2016. All items from the WHO Trial Registration Data Set are included in the registry. ; Fundación Pública Andaluza para la Gestión de la Investigación enSalud de Sevilla (FISEVI), Contact: claram.rosso.sspa@juntadeandalucia.es. This project is a non-commercial, investigator-driven clinical trial, funded through public competitive call by the Instituto de Salud Carlos III (ISCIII), document number: PI15/00439, funded by Instituto de Salud Carlos III, integrated in the national I+D+i 2013-2016 and co-funded by European Union (ERDF/ESF, "Investing in your future"). This study is supported by the Spanish Clinical Research Network and funded by ISCII: study number 16.001. ; Peer reviewed

[Introduction] About 25% of patients with COVID-19 develop acute respiratory distress syndrome (ARDS) associated with a high release of pro-inflammatory cytokines such as interleukin-6 (IL-6). The aim of the SARICOR study is to demonstrate that early administration of sarilumab (an IL-6 receptor inhibitor) in hospitalised patients with COVID-19, pulmonary infiltrates and a high IL-6 or D-dimer serum level could reduce the progression of ARDS requiring high-flow nasal oxygen or mechanical ventilation (non-invasive or invasive). ; [Methods and analysis] Phase II, open-label, randomised, multicentre, controlled clinical trial to study the efficacy and safety of the administration of two doses of sarilumab (200 and 400 mg) plus best available therapy (BAT) in hospitalised adults with COVID-19 presenting cytokine release syndrome. This strategy will be compared with a BAT control group. The efficacy and safety will be monitored up to 28 days postadministration. A total of 120 patients will be recruited (40 patients in each arm). ; [Ethics and dissemination] The clinical trial has been approved by the Research Ethics Committee of the coordinating centre and authorised by the Spanish Agency of Medicines and Medical Products. If the hypothesis is verified, the dissemination of the results could change clinical practice by increasing early administration of sarilumab in adult patients with COVID-19 presenting cytokine release syndrome, thus reducing intensive care unit admissions. ; [Trial registration number] NCT04357860. ; COVID-19 Research Programme. Ministry of Health and Families, Regional Government of Andalusia. Project code COVID-0013-2020.

[Introduction] The rapid worldwide spread of carbapenem-resistant Enterobacteriaceae (CRE) constitutes a major challenge. The aim of the EUropean prospective cohort study on Enterobacteriaceae showing REsistance to CArbapenems (EURECA), which is part of the Innovative Medicines Initiative Joint Undertaking (IMI JU) funded COMBACTE-CARE project, is to investigate risk factors for and outcome determinants of CRE infections to inform randomised clinical trial designs and to provide a historical cohort that could eventually be used for future comparisons with new drugs targeting CRE. ; [Methods] A multicentre (50 sites), multinational (11 European countries), analytical observational project was designed, comprising 3 studies. The aims of study 1 (a prospective cohort study) include characterising the features, clinical management and outcomes of hospitalised patients with intra-abdominal infection, pneumonia, complicated urinary tract infections and bloodstream infections caused by CRE (202 patients in each group). The main outcomes will be 30-day all-cause mortality and clinical response. Study 2 (a nested case–control study) will identify the risk factors for target infections caused by CRE; 248 selected patients from study 1 will be matched with patients with carbapenem-susceptible Enterobacteriaceae (1:1) and with hospitalised patients (1:3) and will provide a historical cohort of patients with CRE infections. Study 3 (a matched cohort study) will follow patients in study 2 in order to assess mortality, length of stay and hospital costs associated with CRE. All patients will be followed for 30 days. Different, up-to-date statistical methods will be applied to come to unbiased estimates for all 3 studies. ; [Ethics and dissemination] Before-study sites will be initiated, approval will be sought from appropriate regulatory agencies and local Ethics Committees of Research or Institutional Review Boards (IRBs) to conduct the study in accordance with regulatory requirements. This is an observational study and therefore no intervention in the diagnosis, management or treatment of the patients will be required on behalf of the investigation. Any formal presentation or publication of data collected from this study will be considered as a joint publication by the participating physician(s) and will follow the recommendations of the International Committee of Medical Journal Editors (ICMJE) for authorship. ; [Trial registration number] NCT02709408. ; The EURECA project is funded by the Innovative Medicine Initiative (IMI), European Union's Seventh Framework Programme (FP7/2007–2013) and EFPIA companies' in-kind contribution (COMBACTE-CARE, grant agreement 115 620). JR-B and AP received funding for research from the Spanish Network for Research in Infectious Diseases (REIPI RD12/0015 and RD16/2016), Instituto de Salud Carlos III, MInisterio de Economía y Competitivad, co-financed by the European Development Regional Fund 'A Way to Achieve Europe' ERDF; BG-G is the recipient of a Río Hortega grant from Instituto de Salud Carlos III (CM 15/00265). ; Peer reviewed

MODERN WP2 study group: Caroline Brossier, Elodie von Dach, Gesuele Renzi, Jacques Schrenzel, Stefanie Bunk, Siri Goepel, Florian Hölzl, Michael Eib, Ingo B.Autenrieth, Álvaro Pascual, Xavier Bertrand, Jelle Scharringa, Patrick Musicha. ; [Objectives] This study aimed to determine rates and risk factors of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) acquisition and transmission within households after hospital discharge of an ESBL-PE-positive index patient. ; [Methods] Two-year prospective cohort study in five European cities. Patients colonized with ESBL-producing Escherichia coli (ESBL-Ec) or Klebsiella pneumoniae (ESBL-Kp), and their household contacts were followed up for 4 months after hospital discharge of the index case. At each follow up, participants provided a faecal sample and personal information. ESBL-PE whole-genome sequences were compared using pairwise single nucleotide polymorphism-based analysis. ; [Results] We enrolled 71 index patients carrying ESBL-Ec (n = 45), ESBL-Kp (n = 20) or both (n = 6), and 102 household contacts. The incidence of any ESBL-PE acquisition among household members initially free of ESBL-PE was 1.9/100 participant-weeks at risk. Nineteen clonally related household transmissions occurred (case to contact: 13; contact to case: 6), with an overall rate of 1.18 transmissions/100 participant-weeks at risk. Most of the acquisition and transmission events occurred within the first 2 months after discharge. The rate of ESBL-Kp household transmission (1.16/100 participant-weeks) was higher than of ESBL-Ec (0.93/100 participant-weeks), whereas more acquisitions were noted for ESBL-Ec (1.06/100 participant-weeks) compared with ESBL-Kp (0.65/100 participant-weeks). Providing assistance for urinary and faecal excretion to the index case by household members increased the risk of ESBL-PE transmission (adjusted prevalence ratio 4.3; 95% CI 1.3–14.1). ; [Conclusions] ESBL-PE cases discharged from the hospital are an important source of ESBL-PE transmission within households. Most acquisition and transmission events occurred during the first 2 months after hospital discharge and were causally related to care activities at home, highlighting the importance of hygiene measures in community settings. ; [Clinical study registration] German Clinical Trials Register, DRKS-ID: DRKS00013250. ; This study was part of a Joint Programming Initiative on Antimicrobial Resistance collaborative research project, under the 2016 Joint Call framework (Transnational Research Projects on the Transmission Dynamics of Antibacterial Resistance). It received funding from the following national research agencies: Instituto de Salud Carlos III (grant no. AC16/00076), Netherlands Organization for Health Research and Development (grant no. AC681055), Swiss National Science Foundation (grant no. 40AR40-173608), German Federal Ministry of Education and Research (grant no. 01KI1830) and Agence Nationale de la Recherche (grant no. ANR-16-JPEC-0007-03). As part of a separate research project, Marlieke de Kraker has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement nos 115523, 115620 and 115737 (Combatting Bacterial Resistance in Europe projects (COMBACTE)), resources of which are composed of financial contribution from the European Union's 7th Framework Programme (FP7/2007±2013) and the European Federation of Pharmaceutical Industries and associations companies' in-kind contribution. Also, Elena Salamanca, Mercedes Delgado and Jesús Rodríguez-Baño received support for research from by the Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0001), co-financed by the European Development Regional Fund 'A way to achieve Europe', Operative Programme Intelligence Growth 2014-2020. ; Peer reviewed

Trial enrichment using gut microbiota derived biomarkers by high-risk individuals can improve the feasibility of randomized controlled trials for prevention of Clostridioides difficile infection (CDI). Here, we report in a prospective observational cohort study the incidence of CDI and assess potential clinical characteristics and biomarkers to predict CDI in 1,007 patients ≥ 50 years receiving newly initiated antibiotic treatment with penicillins plus a beta-lactamase inhibitor, 3rd/4th generation cephalosporins, carbapenems, fluoroquinolones or clindamycin from 34 European hospitals. The estimated 90-day cumulative incidences of a first CDI episode is 1.9% (95% CI 1.1-3.0). Carbapenem treatment (Hazard Ratio (95% CI): 5.3 (1.7-16.6)), toxigenic C. difficile rectal carriage (10.3 (3.2-33.1)), high intestinal abundance of Enterococcus spp. relative to Ruminococcus spp. (5.4 (2.1-18.7)), and low Shannon alpha diversity index as determined by 16 S rRNA gene profiling (9.7 (3.2-29.7)), but not normalized urinary 3-indoxyl sulfate levels, predicts an increased CDI risk. ; This research project was supported by the Innovative Medicines Initiative Joint Undertaking (IMI JU) under grant agreement No. 115523, the Combatting Bacterial Resistance in Europe (COMBACTE) consortium, resources of which are composed of financial contribution from the European Union Seventh Framework Program (FP7/2007–2013) and Da Volterra, as a member of the European Federation of Pharmaceutical Industries and Associations (EFPIA) companies in kind and cash contribution.