EUropean prospective cohort study on Enterobacteriaceae showing REsistance to CArbapenems (EURECA): a protocol of a European multicentre observational study

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.Innovative Medicine Initiative (IMI)European Union's Seventh Framework Programme (FP7)Spanish Network for Research in Infectious Diseases [REIPI RD12/0015, RD16/2016

Genomic Evolution of Two Acinetobacter baumannii Clinical Strains from ST-2 Clones Isolated in 2000 and 2010 (ST-2_clon_2000 and ST-2_clon_2010)

Acinetobacter baumannii is a successful nosocomial pathogen due to its ability to persist in hospital environments by acquiring mobile elements such as transposons, plasmids, and phages. In this study, we compared two genomes of A. baumannii clinical strains isolated in 2000 (ST-2_clon_2000) and 2010 (ST-2_clon_2010) from GenBank project PRJNA308422

Clinical efficacy of β-lactam/β-lactamase inhibitor combinations for the treatment of bloodstream infection due to extended-spectrum β-lactamase- producing Enterobacteriaceae in haematological patients with neutropaenia: a study protocol for a retrospect observational study (BICAR).

Introduction: Bloodstream infection (BSI) due to extended-spectrum β-lactamase-producing Gram- negative bacilli (ESBL-GNB) is increasing at an alarming pace worldwide. Although β-lactam/β- lactamase inhibitor (BLBLI) combinations have been suggested as an alternative to carbapenems for the treatment of BSI due to these resistant organisms in the general population, their usefulness for the treatment of BSI due to ESBL-GNB in haematological patients with neutropaenia is yet to be elucidated. The aim of the BICAR study is to compare the efficacy of BLBLI combinations with that of carbapenems for the treatment of BSI due to an ESBL-GNB in this population. Methods and analysis: A multinational, multicentre, observational retrospective study. Episodes of BSI due to ESBL-GNB occurring in haematological patients and haematopoietic stem cell transplant recipients with neutropaenia from 1 January 2006 to 31 March 2015 will be analysed. The primary end point will be case- fatality rate within 30 days of onset of BSI. The secondary end points will be 7-day and 14-day case- fatality rates, microbiological failure, colonisation/ infection by resistant bacteria, superinfection, intensive care unit admission and development of adverse events. Sample size: The number of expected episodes of BSI due to ESBL-GNB in the participant centres will be 260 with a ratio of control to experimental participants of 2. Ethics and dissemination: The protocol of the study was approved at the first site by the Research Ethics Committee (REC) of Hospital Universitari de Bellvitge. Approval will be also sought from all relevant RECs. Any formal presentation or publication of data from this study will be considered as a joint publication by the participating investigators and will follow the recommendations of the International Committee of Medical Journal Editors (ICMJE). The study has been endorsed by the European Study Group for Bloodstream Infection and Sepsis (ESGBIS) and the European Study Group for Infections in Compromised Hosts (ESGICH).Ministerio de Economía y Competitividad REIPI RD12/001

Resultados del programa “Estrategias de Autoanálisis Ocupacional” en personas con daño cerebral adquirido

OBJETIVOS. Analizar los efectos del programa: Estrategias de Autoanálisis Ocupacional en personas con daño cerebral adquirido (DCA). MATERIAL Y MÉTODOS. Diseño del estudio: Estudio pretest-postest compuesto por un grupo que recibía el programa de Estrategias de Autoanálisis ocupacional. Participantes: 5 hombres y 2 mujeres con DCA con una media de edad de 51.8 años, miembros de una Asociación de DCA. Intervención: Se realizó el Programa de “Estrategias de Autoanálisis Ocupacional” que pretende que los participantes aprendan cuáles son sus limitaciones y apoyos para la participación ocupacional y que trabajen para la consecución de objetivos individuales y/o grupales de mejora de su equilibrio ocupacional. Emplea 2 herramientas metodológicas: el Modelo de la Ocupación Humana y el Ver Juzgar Actuar. Los participantes asistieron a 21 sesiones grupales semanales de 90 minutos de duración. Además, realizaron 3 sesiones individuales. Los módulos trabajados fueron 1) ocupación, dificultad y salud, 2) equilibrio ocupacional, 3) estrategias de adaptación a las dificultades de la vida diaria y 4) relaciones sociales. Herramientas de Evaluación: Los datos cuantitativos se recogieron en entrevistas individuales al inicio y al final. Se utilizó el Cuestionario SF-36 para medir la salud percibida(Alonso, Prieto, &Antó, 1995). Con el objetivo de evaluar los roles ocupacionales, se empleó la parte I del Listado de Roles (Colón &Haertlein, 2002). Los datos cualitativos se obtuvieron a través de 2 herramientas: el cuaderno de seguimiento individual y un grupo focal realizado al final de la intervención. RESULTADOS. Tras la intervención en el programa, encontramos un incremento significativo (p<0.05) en la subescala energía (Z=-2.2; p=.028) y marginalmente significativo (p=.058) en el componente físico del Cuestionario SF-36. Asimismo, encontramos un aumento marginalmente significativo del número de roles que los participantes deseaban involucrarse en el futuro (Z=.707; p=.072). Los participantes aprendieron a ser más conscientes de aspectos necesarios para mejorar su participación ocupacional, como su motivación y deseo de superación. “He aprendido que con esfuerzo, dedicación y constancia te puedes servir o valer por ti mismo por muchas dificultades que tengas” (Javier, 28 años) El ambiente social y el propio grupo de trabajo aparecieron como apoyos para su participación ocupacional. “Para uno es un orgullo hacer las cosas, pero hacerlas y que los demás las vean, es un reto”(Alejandro, 54 años) CONCLUSIÓN. El programa “Estrategias de Autoanálisis Ocupacional”en participantes con daño cerebral mejoró diferentes aspectos de la salud percibida e incrementó la toma de conciencia de la motivación y del apoyo social. Estos resultados apoyan los obtenidos por Ng y cols (2013), en donde, de igual modo, se fomentó la participación ocupacional en personas con DCA, incidiendo en trabajar la autoeficacia y el compromiso con los objetivos que uno/a quiere alcanzar.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Opportunities for antibiotic optimisation and outcome improvement in patients with negative blood cultures: study protocol for a cluster-­randomised crossover trial, the NO-­BACT study.

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.Instituto de Salud Carlos III PI17 / 01809Plataforma Española de Investigación Clínica y Ensayos Clínicos, SCReN (Red Española de Investigación Clínica), financiada por la Subdirección General de Evaluación y Promoción de la Investigación ISCIII: PT17 / 0017/0012. Cofinanciado por el Fondo Europeo de Desarrollo Regional (FEDER)

An International Prospective Cohort Study To Validate 2 Prediction Rules for Infections Caused by Third-generation Cephalosporin-resistant Enterobacterales

Background The possibility of bloodstream infections caused by third-generation cephalosporin-resistant Enterobacterales (3GC-R-BSI) leads to a trade-off between empiric inappropriate treatment (IAT) and unnecessary carbapenem use (UCU). Accurately predicting 3GC-R-BSI could reduce IAT and UCU. We externally validate 2 previously derived prediction rules for community-onset (CO) and hospital-onset (HO) suspected bloodstream infections. Methods In 33 hospitals in 13 countries we prospectively enrolled 200 patients per hospital in whom blood cultures were obtained and intravenous antibiotics with coverage for Enterobacterales were empirically started. Cases were defined as 3GC-R-BSI or 3GC-R gram-negative infection (3GC-R-GNI) (analysis 2); all other outcomes served as a comparator. Model discrimination and calibration were assessed. Impact on carbapenem use was assessed at several cutoff points. Results 4650 CO infection episodes were included and the prevalence of 3GC-R-BSI was 2.1% (n = 97). IAT occurred in 69 of 97 (71.1%) 3GC-R-BSI and UCU in 398 of 4553 non–3GC-R-BSI patients (8.7%). Model calibration was good, and the AUC was .79 (95% CI, .75–.83) for 3GC-R-BSI. The prediction rule potentially reduced IAT to 62% (60/97) while keeping UCU comparable at 8.4% or could reduce UCU to 6.3% (287/4553) while keeping IAT equal. IAT and UCU in all 3GC-R-GNIs (analysis 2) improved at similar percentages. 1683 HO infection episodes were included and the prevalence of 3GC-R-BSI was 4.9% (n = 83). Here model calibration was insufficient. Conclusions A prediction rule for CO 3GC-R infection was validated in an international cohort and could improve empirical antibiotic use. Validation of the HO rule yielded suboptimal performance

Analysis of the challenges in implementing guidelines to prevent the spread of multidrug-resistant gram-negatives in Europe

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

Social media posts and online search behaviour as early-warning system for MRSA outbreaks

Background: Despite many preventive measures, outbreaks with multi-drug resistant micro-organisms (MDROs) still occur. Moreover, current alert systems from healthcare organizations have shortcomings due to delayed or incomplete notifications, which may amplify the spread of MDROs by introducing infected patients into a new healthcare setting and institutions. Additional sources of information about upcoming and current outbreaks, may help to prevent further spread of MDROs. The study objective was to evaluate whether methicillin-resistant Staphylococcus aureus (MRSA) outbreaks could be detected via social media posts or online search behaviour; if so, this might allow earlier detection than the official notifications by healthcare organizations. Methods: We conducted an exploratory study in which we compared information about MRSA outbreaks in the Netherlands derived from two online sources, Coosto for Social Media, and Google Trends for search behaviour, to the mandatory Dutch outbreak notification system (SO-ZI/AMR). The latter provides information on MDRO outbreaks including the date of the outbreak, micro-organism involved, the region/location, and the type of health care organization. Results: During the research period of 15 months (455 days), 49 notifications of outbreaks were recorded in SO-ZI/ AMR. For Coosto, the number of unique potential outbreaks was 37 and for Google Trends 24. The use of social media and online search behaviour missed many of the hospital outbreaks that were reported to SO-ZI/AMR, but detected additional outbreaks in long-term care facilities. Conclusions: Despite several limitations, using information from social media and online search behaviour allows rapid identification of potential MRSA outbreaks, especially in healthcare settings with a low notification compliance. When combined in an automated system with real-time updates, this approach might increase early discovery and subsequent implementation of preventive measures.EPI-Net COMBACTE-MAGNET project 115737Unión Europea FP7/2007–201

Biofilm formation at the solid-liquid and air-liquid interfaces by Acinetobacter species

Abstract Background: The members of the genus Acinetobacter are Gram-negative cocobacilli that are frequently found in the environment but also in the hospital setting where they have been associated with outbreaks of nosocomial infections. Among them, Acinetobacter baumannii has emerged as the most common pathogenic species involved in hospital-acquired infections. One reason for this emergence may be its persistence in the hospital wards, in particular in the intensive care unit; this persistence could be partially explained by the capacity of these microorganisms to form biofilm. Therefore, our main objective was to study the prevalence of the two main types of biofilm formed by the most relevant Acinetobacter species, comparing biofilm formation between the different species. Findings: Biofilm formation at the air-liquid and solid-liquid interfaces was investigated in different Acinetobacter spp. and it appeared to be generally more important at 25°C than at 37°C. The biofilm formation at the solid-liquid interface by the members of the ACB-complex was at least 3 times higher than the other species (80-91% versus 5-24%). In addition, only the isolates belonging to this complex were able to form biofilm at the air-liquid interface; between 9% and 36% of the tested isolates formed this type of pellicle. Finally, within the ACB-complex, the biofilm formed at the air-liquid interface was almost 4 times higher for A. baumannii and Acinetobacter G13TU than for Acinetobacter G3 (36%, 27% & 9% respectively). Conclusions: Overall, this study has shown the capacity of the Acinetobacter spp to form two different types of biofilm: solid-liquid and air-liquid interfaces. This ability was generally higher at 25°C which might contribute to their persistence in the inanimate hospital environment. Our work has also demonstrated for the first time the ability of the members of the ACB-complex to form biofilm at the air-liquid interface, a feature that was not observed in other Acinetobacter species