14 research outputs found
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
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)
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
Epidemiology, Clinical Features, and Antimicrobial Resistance of Invasive<i>Escherichia Coli</i>Disease in Patients Admitted in Tertiary Care Hospitals
Background Invasive Escherichia coli disease (IED), including bloodstream infection, sepsis, and septic shock, can lead to high hospitalization and mortality rates. This multinational study describes the clinical profile of patients with IED in tertiary care hospitals. Methods We applied clinical criteria of systemic inflammatory response syndrome (SIRS), sepsis, or septic shock to patients hospitalized with culture-confirmed E coli from urine or a presumed sterile site. We assessed a proposed clinical case definition against physician diagnoses. Results Most patients with IED (N = 902) were adults aged >= 60 years (76.5%); 51.9%, 25.1%, and 23.0% of cases were community-acquired (CA), hospital-acquired (HA), and healthcare-associated (HCA), respectively. The urinary tract was the most common source of infection (52.3%). Systemic inflammatory response syndrome, sepsis, and septic shock were identified in 77.4%, 65.3%, and 14.1% of patients, respectively. Patients >60 years were more likely to exhibit organ dysfunction than those = 75 years, 22.2%), with an increase across IED acquisition settings (HA, 28.3%; HCA, 21.7%; CA, 15.2%). Noticeably, 77.8% of patients initiated antibiotic use on the day of culture sample collection. A total of 65.6% and 40.8% of E coli isolates were resistant to >= 1 agent in >= 1 or >= 2 drug class(es). A 96.1% agreement was seen between the proposed clinical case definition and physician's diagnoses of IED. Conclusions This study contributes valuable, real-world data about IED severity. An accepted case definition could promote timely and accurate diagnosis of IED and inform the development of novel preventative strategies. IED is associated with prolonged hospitalization, extensive medical resource use, and mortality. Many patients develop SIRS, sepsis, and septic shock. The main source of infection is the urinary tract. An IED clinical case definition could promote timely and accurate diagnosis
Targeted Simplification Versus Antipseudomonal Broad-Spectrum Beta-Lactams in Patients With Bloodstream Infections Due to Enterobacteriaceae (SIMPLIFY): A Study Protocol for a Multicentre, Open-Label, Phase III Randomised, Controlled, Non-Inferiority Clinical Trial.
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.Instituto de Salud Carlos III (ISCIII): PI15/00439, integrado en el Plan Nacional de I+D+i 2013-2016 y cofinanciado por la Unión Europea (ERDF/ESF, “Investing in your future”)
Quality indicators for responsible antibiotic use in the inpatient setting: a systematic review followed by an international multidisciplinary consensus procedure
Background
This study was conducted as part of the Driving Reinvestment in Research and Development and Responsible Antibiotic Use (DRIVE-AB) project and aimed to develop generic quality indicators (QIs) for responsible antibiotic use in the inpatient setting.
Methods
A RAND-modified Delphi method was applied. First, QIs were identified by a systematic review. A complementary search was performed on web sites of relevant organizations. Duplicates were removed and disease and patient-specific QIs were combined into generic indicators. The relevance of these QIs was appraised by a multidisciplinary international stakeholder panel through two questionnaires and an in-between consensus meeting.
Results
The systematic review retrieved 70 potential generic QIs. The QIs were appraised by 25 international stakeholders with diverse backgrounds (medical community, public health, patients, antibiotic research and development, regulators, governments). Ultimately, 51 QIs were selected in consensus. QIs with the highest relevance score included: (i) an antibiotic plan should be documented in the medical record at the start of the antibiotic treatment; (ii) the results of bacteriological susceptibility testing should be documented in the medical record; (iii) the local guidelines should correspond to the national guidelines but should be adapted based on local resistance patterns; (iv) an antibiotic stewardship programme should be in place at the healthcare facility; and (v) allergy status should be taken into account when antibiotics are prescribed.
Conclusions
This systematic and stepwise method combining evidence from literature and stakeholder opinion led to multidisciplinary international consensus on generic inpatient QIs that can be used globally to assess the quality of antibiotic use
Real world evidence of calcifediol or vitamin D prescription and mortality rate of COVID-19 in a retrospective cohort of hospitalized Andalusian patients
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, CB16/10/00501 from CIBERFES-ISCIII; PI19/00033 from the ISCIII, co-funded with ERDF; COVID-011-2020 from Consejería de Salud y Familia. Te authors also acknowledge Junta de Andalucía for the postdoctoral contract of Carlos Loucera (PAIDI2020- DOC_00350) co-funded by the European Social Fund (FSE) 2014-2020.Ye