Re: ECDC: Summary of the latest data on antibiotic resistance in the European Union
[Source: European Centre for Disease Prevention and Control (ECDC), full PDF document: (
LINK). Excerpts.]
TECHNICAL REPORT
Carbapenemase-producing bacteria in Europe. Interim results from the European survey on carbapenemase-producing Enterobacteriaceae (EuSCAPE) project 2013
www.ecdc.europa.eu
This report was commissioned by the European Centre for Disease Prevention and Control (ECDC), coordinated by Barbara Albiger, and produced by Corinna Glasner, Hajo Grundmann of the University Medical Center Groningen (UMCG).
Contributing authors: Hajo Grundmann, Corinna Glasner, Anna-Pelagia Magiorakos, Liselotte H?gberg-Diaz, Dominique L. Monnet, Barbara Albiger.
Data analysis: Corinna Glasner, Hajo Grundmann, Barbara Albiger, Liselotte H?gberg-Diaz, Dominique L. Monnet.
Maps: Tjibbe Donker.
Acknowledgements: EuSCAPE scientific advisory board: Arjana Tambić Andra?ević, Rafael Cant?n, Yehuda Carmeli, Alexander W. Friedrich, Christian G. Giske, Youri Glupczynski, Marek Gniadkowski, Laurent Poirel, Gian Maria Rossolini, Harald Seifert, Alkiviadis Vatopoulos, Timothy Walsh, Neil Woodford, are acknowledged for providing valuable comments and scientific advice during the production of the questionnaire and the report.
National Experts: Albania ? Andi Koraqi; Austria ? Petra Apfalter; Belgium ? Youri Glupczynski; Bosnia and Herzegovia ? Tatjana Markovic; Bulgaria ? Tanya Strateva; Croatia ? Arjana Tambić Andra?ević; Cyprus ? Despo Pieridou-Bagatzouni; Czech Republic ? Jaroslav Hrabak; Denmark ? Anette M. Hammerum; Estonia ? Marina Ivanova; Finland ? Jari Jalava; France ? Bruno Coignard; Germany ? Martin Kaase; Greece ? Alkiviadis Vatopoulos; Hungary ? ?kos T?th; Iceland ? Hordur Hardarson; Ireland ? Teck Wee Boo; Israel ? Yehuda Carmeli; Italy ? Annalisa Pantosti; Kosovo ? Lul Raka; Latvia ? Arta Balode; Lithuania ? Jolanta Miciuleviciene; Luxembourg ? Monique Perrin-Weniger; Malta ? Nina Nestorova; Montenegro ? Gordana Mijovic; The Netherlands ? Henk Bijlmer; Norway ? ?rjan Samuelsen; Poland ? Dorota Zabicka; Portugal ? Manuela Cani?a; The former Yugoslav Republic of Macedonia ? Ana Kraftandzieva; Romania ? Maria Damian; Serbia ? Zora Jelesić; Slovakia ? Milan Nik?; Slovenia ? Mateja Pir?; Spain ? Jes?s Oteo; Sweden ? Christian G. Giske; Turkey ? Deniz G?r; United Kingdom ? Neil Woodford, UK-Scotland ? Camilla Wiuff, are acknowledged for answering the survey and providing the country specific data for this report.
Patrice Nordmann and David M. Livermore are acknowledged for their feedback and input during the production of the report.
Suggested citation: European Centre for Disease Prevention and Control. Carbapenemase-producing bacteria in Europe: interim results from the European Survey on carbapenemase-producing Enterobacteriaceae (EuSCAPE) project. Stockholm: ECDC; 2013.
Stockholm, November 2013 / ISBN 978-92-9193-507-9 / doi 10.2900/91714
Catalogue number TQ-01-13-572-EN-N
? European Centre for Disease Prevention and Control, 2013
Reproduction is authorised, provided the source is acknowledged
Executive summary
The spread of carbapenem-non-susceptible bacteria, more specifically of carbapenemase-producing Enterobacteriaceae and carbapenem-resistant Acinetobacter baumannii, is a threat to healthcare and patient safety in Europe, although its exact prevalence in healthcare facilities and within the community in Europe is unknown.
The European Centre for Disease Prevention and Control (ECDC) is currently funding a project on carbapenemaseproducing bacteria in Europe.
The first part of the project was a survey to gather information about the spread of carbapenemase-producing Enterobacteriaceae (CPE) and carbapenem-resistant A. baumannii (CRAb) in Europe, on public health responses and on available national guidance on detection, surveillance, prevention and control. The survey also investigated the laboratory capacity for diagnosis and surveillance at the national level.
Between 8 February and 14 March 2013, 39 national experts from the 28 European Union (EU) Member States, Iceland, Norway, the seven EU enlargement countries and Israel were invited to complete the survey. The present report summarises the results of this survey and demonstrates that CPE and CRAb are increasingly spreading in Europe, highlighting the urgent need for a coordinated European effort on early diagnosis, active surveillance, and guidance on infection prevention and control measures.
Introduction
The Enterobacteriaceae form part of the commensal human gut flora and are frequently the cause of communityand healthcare-associated infections (HAI). Acinetobacter species are opportunistic pathogens that are being increasingly isolated from healthcare settings, mostly from intensive care units and from immunocompromised patients. Treatment of infections due to Acinetobacter spp. has become more challenging, since a large percentage of these bacteria have become resistant to many and sometimes all antibiotics to which they were once susceptible.
Over the last decade, Gram-negative bacteria in Europe and worldwide (i.e. Enterobacteriaceae and Acinetobacter spp.) have become increasingly resistant to first- and second-line antibiotics (e.g. beta-lactam antibiotics, fluoroquinolones and aminoglycosides) [1]. Resistance to extended-spectrum beta-lactam antibiotics (e.g. thirdgeneration cephalosporins) due to the production of extended-spectrum beta-lactamases (ESBLs) continues to increase in Enterobacteriaceae [1]. Carbapenems are a class of beta-lactam antibiotics with very broad activity and have therefore become the empirical treatment option in countries where infections due to ESBL-producing bacteria are common, as well as an important treatment option for multidrug-resistant Acinetobacter spp..
Resistance to carbapenems in Enterobacteriaceae and in Acinetobacter spp. is linked to either decreased permeability or to the enzymatic breakdown of the antibiotic by carbapenemases. The most frequent carbapenemases in Enterobacteriaceae reported in Europe are: the Klebsiella pneumoniae carbapenemase (KPC), the Verona integron-encoded metallo-beta-lactamase (VIM), the IMP-type metallo-beta-lactamase (IMP), the New Delhi metallo-beta-lactamases (e.g. NDM-1) and the OXA-48-like carbapenem-hydrolysing oxacillinases [2,3]. The following Acinetobacter species, A. baumannii, A. nosocomialis and A. pittii: belong to the Acinetobacter baumannii group. For the remainder of this report, these three species will be collectively designated as A. baumannii sensu lato. A.baumannii possesses the intrinsic oxacillinase OXA-51 that confers resistance to carbapenems only when over-expressed. The most frequent mechanism leading to carbapenem resistance in A. baumannii is mediated by the acquired oxacillinases OXA-23-like, OXA-24-like, OXA-58-like, OXA-143-like and OXA-235. Metallo-β-lactamases, such as IMP, VIM and others have only rarely been encountered in A. baumannii, although NDMproducing A. baumannii isolates have increasingly been reported in Europe [4-6].
The rapid and global expansion of CPE and CRAb is a threat to healthcare and patient safety worldwide, as it seriously curtails the ability to cure infections. Infections due to CPE are associated with higher in-hospital mortality [7-9].
During the annual meeting of the European Antimicrobial Resistance Surveillance System in Athens in 2009, the need for a European-wide consultation about the increasing occurrence of CPE was recognised among European experts. At a follow-up workshop at the Dutch National Institute for Public Health and the Environment (RIVM) in April 2010, experts in the surveillance of antimicrobial resistance in Enterobacteriaceae from 31 European countries established a novel epidemiological staging system to describe the magnitude of CPE and provided recommendations to address this public health issue in a concerted manner [10]. Following the meeting, a survey was carried out, providing valuable insights into the prevalence of different carbapenemases and the degree of spread of CPE in the EU Member States and three European Economic Area (EEA)/European Free Trade Association (EFTA) countries [10].
In November 2010, ECDC published a risk assessment on the spread of NDM-1-producing Enterobacteriaceae in the EU Member States, which also reported on the availability of national guidance on detection, surveillance, notification and control of NDM-1 and other carbapenemase-producing Enterobacteriaceae in these countries [11].
In 2011, ECDC issued an update of this risk assessment and published a broader risk assessment on the spread of carbapenemase-producing Enterobacteriaceae (CPE) through patient transfer between healthcare facilities, with special emphasis on cross-border transfer [12,13]. In 2012, Canton et al. estimated the extent and spread of CPE in Europe based on available published data [14]. Most recently, Levy Hara et al. published recommendations from an international working group for the detection, treatment and prevention of CPE [15]. The increasing number of reports on CRAb outbreaks and the emergence of new CRAb clones in European hospitals suggest that CRAb has become another menace in European hospitals [4,6,16-27]. There is consensus among experts that surveillance of CPE and CRAb is crucial for the implementation of effective infection prevention and control.
In April 2012, ECDC published an open call for tender for a European project on carbapenemase-producing bacteria with the following aim: to improve the understanding of the epidemiology and occurrence of carbapenemase-producing bacteria in Europe; to build laboratory capacity for diagnosis and surveillance at the national and European level; and to develop a laboratory-based network in the EU Member States and EEA and the EU enlargement countries that is capable of providing information on the prevalence of carbapenemase-producing bacteria in Europe.
The European Survey on carbapenemase-producing Enterobacteriaceae (EuSCAPE) project is implementing some of the recommendations published in 2010, such as assessing the existing laboratory capacity, building the capacity of reference diagnostics, standardising the detection of carbapenemase-producing bacteria, and developing a structured survey to obtain a more accurate estimate of carbapenemase-producing bacteria in Europe [10,28].
The EuSCAPE project is divided into three parts, whose goals are:
- To gather information about the spread of CPE and CRAb in Europe on; public health responses; on available national guidance on detection, surveillance, prevention and control; and about the laboratory capacity for diagnosis and surveillance using a survey sent to 39 national experts in 38 European countries, (8 February 2013?14 March 2013)
- To host a capacity building workshop for national laboratory experts to be further informed about the identification and confirmation of CPE (5?6 September 2013, Vari, Greece)
- To carry out an external quality assessment followed by a structured survey collecting European isolates of CPE together with data on CPE-related infections in 38 European countries (November 2013?May 2014).
This interim report summarises the results of the survey amongst the national experts from the 28 Member States, Iceland, Norway, the seven EU enlargement countries and Israel.
Methodology
The purpose of the survey was to gather information about the spread of CPE and CRAb in Europe, on public health responses and on available national guidance on detection, surveillance, prevention and control. The survey also assessed the laboratory capacity for diagnosis and surveillance at the national and European level.
Description of the survey
The survey was derived from a field-tested version used during previous similar surveys [10,11]. It was based on a questionnaire and divided into three sections:
- Section 1: 13 questions exploring the experts? knowledge and awareness of the current occurrence of CPE and CRAb and supporting a self-assessment of the spread of CPE and CRAb according to a previously established epidemiological staging system (Table 1);
- Section 2: 22 questions gathering information about existing national guidance documents for reporting, surveillance, use of reference laboratory services and infection control for CPE and CRAb;
- Section 3: 26 questions gathering information about the existing laboratory capacity at the national level in each country in preparation of the second and third phase of the EuSCAPE project, i.e. the capacity building workshop (5-6 September 2013) and the structured survey (November 2013 − May 2014).
The survey questions were discussed and validated by an expert panel, composed of the EuSCAPE Management Team, the EuSCAPE Scientific Advisory Board and ECDC (Annex 1). Three types of questions were included: yes/no, multiple choice and open questions with possibility of free text answers (for details about the questionnaire, please see Annex 2).
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Composition of the Scientific Advisory Board
A panel of scientific experts (Scientific Advisory Board) was invited to provide expert support to the EuSCAPE project (Annex 1). The members of the EuSCAPE Scientific Advisory Board were selected for their broad expertise in the field of CPE and CRAb.
Some members of the Scientific Advisory Board also represented relevant scientific and professional organisations in the field of antimicrobial resistance, i.e. the European Committee on Antibiotic Susceptibility Testing (EUCAST), the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), the European Network On Carbapenemase-producing bacteria, the European Surveillance for Antimicrobial Resistance (EARS‐Net), and the European Study Group for Antimicrobial Resistance Surveillance (ESGARS). Care was taken to choose experts from different geographical regions for an adequate European perspective (Annex 1). Additional expert support to the EuSCAPE project was provided by two independent external experts (Annex 1).
Selection of the national experts
In each of the 38 European countries, a national expert (NE) with acknowledged laboratory and/or epidemiological experience was identified. Twenty-three of these NEs are employed at reference laboratories. The NEs were chosen among EARS-Net contact points, experts from national reference laboratories and ECDC Coordinating Competent Bodies (National Focal Point for antimicrobial resistance and National Focal Points for microbiology).
The United Kingdom was represented by two NEs. The list of NEs was validated by ECDC and represents the EuSCAPE Working Group (Annex 1).
Description of the survey tool
The NEs were invited to answer the questionnaire online between 8 February and 14 March 2013 using the Survey Monkey software and questionnaire tool Analysis, evaluation and representation of the answers to the survey
Answers from the NEs were compiled in a database. When necessary, NEs were contacted by e-mail or telephone for clarification, and corrections were made accordingly. The NEs answered the questionnaire based on their knowledge of the national clinical and microbiological data or on their personal judgement.
Since there were concerns from some of the NEs that under-detection and/or under-reporting most likely affected the certainty of the staging of their country, stage designations for CPE were considered uncertain if two or more of the following criteria were met:
- the NE reported a lack of awareness about the current epidemiology of CPE in the country;
- the NE reported potential under-detection and under-reporting of CPE in the country;
- the NE expressed uncertainty during the clarifications sought by e-mail or telephone;
- when CPE had been reported to or from other countries but NEs could not independently verify existing sources in their own country.
Uncertainty for the epidemiological stage of CPE is represented on the maps presented in this report (Figure 3 and Figure 5).
As surveillance and reporting of CRAb are not performed routinely at this time, and because fewer national reference laboratory structures for CRAb are in place in European countries, most NEs highlighted that the exact epidemiology of CRAb remains uncertain in their country. There is a clear need for data on CRAb for all participating countries and therefore, the stage designations for CRA might be taken with caution for all participating countries. Hence, it was chosen not to highlight uncertainty in the corresponding map (Figure 7).
The answers of the NEs are presented individually for each country in all tables and figures, except for Figures 2, 4 6, 8 and 9, where the answers were aggregated. The answers of the NEs were based on their knowledge of the epidemiological situation of CPE and CRAb at the time of the survey (8 February?14 March 2013). This situation might have evolved and be different at the time of the publication of this report. If so, and if informed by the NEs, the changes are presented in the discussion.
Results
Epidemiology of carbapenemase-producing bacteria in Europe
All NEs completed the online questionnaire and applied the epidemiological staging system (Table 1) to describe the magnitude of the spread of CPE and CRAb in their respective countries (Figure 2). Comparison of the epidemiological stages of CPE and CRAb suggests that CRAb have a broader dissemination than CPE in Europe. For CRAb, 12 countries reported stage 4 or 5 (inter-regional spread or an endemic situation), whereas only six countries reported the same extent for CPE (Figure 2).
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