The spread of carbapenemase-producing Enterobacteriaceae (CPE) is a threat to healthcare delivery, although its extent differs substantially from country to country. In February 2013, national experts from 39 European countries were invited to self-assess the current epidemiological situation of CPE in their country. Information about national management of CPE was also reported. The results highlight the urgent need for a coordinated European effort on early diagnosis, active surveillance, and guidance on infection control measures.
The present report summarises the results from 39 European countries of a self-assessment of the epidemiological stage and the management of carbapenemase-producing Enterobacteriaceae (CPE) at national level.
CPE are an emerging threat to healthcare and are frequently resistant to many other antibiotics than carbapenems [1,2] leaving few treatment options. The extent, to which healthcare systems have already been affected, however, differs substantially from country to country. Following a previous initiative, a group of European experts is implementing the European Survey on CPE (EuSCAPE) in an effort to update assessments of the nature and scale of CPE spread in Europe . The current programme receives financial support from the European Centre for Disease Prevention and Control (ECDC). The aim of this study is to obtain a more accurate and timely estimate of CPE prevalence in European countries and to support reference laboratory-capacity building to prevent and control the spread of CPE in Europe.
Development of a questionnaire and collection of information
A Scientific Advisory Board of European experts in the field of carbapenemase-producing bacteria was invited to provide scientific advice in support of the EuSCAPE programme management team. A questionnaire was devised and modified from a ‘field-tested’ version used during previous similar surveys . The questionnaire was divided into two sections. The first section (13 questions) explored the experts’ knowledge and awareness of the current occurrence of CPE according to a previously-established epidemiological staging system [1,3]. In brief, the system captures seven consecutive stages in the national spread of these organisms. The seven stages are described in Table 1.
Table 1. Description of the epidemiological stages of carbapenemase-producing Enterobacteriaceae (CPE)
The second section (22 questions) collected information about existing requirements, structures and guidance documents for reporting, surveillance, use of reference laboratory services and infection control for CPE. The questionnaire is available from the corresponding author.
In each of the 39 European countries (i.e. 27 European Union (EU) Member States, all European Economic Area (EEA)/ European Free Trade Association (ETFA) countries except Lichtenstein, and all EU enlargement countries, as well as Israel), a national expert (NE) with acknowledged laboratory and/or epidemiological experience was identified (for the United Kingdom two NEs participate in this questionnaire survey). The NEs were chosen among European Antimicrobial Resistance Surveillance Network (EARS-Net) contact points, experts from national reference diagnostic laboratories and ECDC-coordinating competent bodies. The list of NEs was validated by ECDC and represents the EuSCAPE Working Group. The NEs were invited to answer the questionnaire online (http://SurveyMonkey.net, SurveyMonkey Corporation, Portland, USA).
Answers from the NEs were compiled and analysed. When necessary, NEs were contacted by e-mail or telephone for clarification, and corrections were made accordingly. The epidemiological stage of some countries was considered as uncertain when (i) the NE reported a lack of awareness about the current epidemiology of CPE in their country, (ii) the answer of the NE indicated considerable underdetection and underreporting of CPE in their country, (iii) the comments made by the NE by e-mail or telephone indicated uncertainty and/or (iv) when frequent introductions into other countries have been described but the NE could not independently support this observation by own sources. In the maps (Figure), this uncertainty was indicated by displaying the respective country as hatched.
All NEs completed the online questionnaire. Thirty-seven NEs declared that they were aware of the current epidemiology of CPE in their country and all rated the occurrence and spread of CPE in their country using the previously established epidemiological staging system (Figure and Table 1). Nevertheless, only 26 NEs could self-assess their current situation with certainty.
Figure. Occurrence of carbapenemase-producing Enterobacteriaceae (CPE) in 39 European countries based on self-assessment by respective national experts, 2013
Table 2. Comparison of epidemiological stages of carbapenemase-producing Enterobacteriaceae (CPE) in 39 European countries, 2010, 2012 and 2013
Three countries (Iceland, Montenegro and the former Yugoslav Republic of Macedonia) reported no cases of CPE in their country. Sporadic cases, single or sporadic hospital outbreaks were reported by NEs from 22 countries. For 11 countries, regional or national spread was reported, whereas for three countries (Greece, Italy and Malta) NEs reported that CPE are regularly isolated from patients in most hospitals, corresponding to the endemic stage (Table 2*).
Among the 31 countries that participated in both the 2010 and 2013 assessments, 17 reported a higher stage by 2013; likewise, by 2013, the number of countries with regional or inter-regional spread or an endemic situation increased from seven to 13 (Table 2*). Some countries expressed concerns that underdetection or underreporting, or both, could affect the certainty of the stage of their countries (Figure).
Thirty-three of the NEs indicated that Klebsiella pneumoniae was the most frequent Enterobacteriaceae species to produce carbapenemases in their country. Overall, K. pneumoniae carbapenemase-producing Enterobacteriaceae (KPC) have attained the widest distribution, whereas strains with New Delhi metallo (NDM)-beta-lactamase – although responsible for occasional hospital outbreaks in few countries – have not reached such a wide distribution in European countries (Figure).
Table 3* displays the level of national management of CPE, based on existing surveillance, reference systems, and guidance in the 39 countries. Thirty and 29 of 39 countries reported having a dedicated surveillance system for CPE and a dedicated reference laboratory for CPE, respectively. Twenty-three reported having a system to notify CPE cases to health authorities, mostly on a mandatory basis. Only 22 countries reported having national recommendations or guidelines on infection control measures to prevent the spread of CPE; one country reported having such recommendation or guideline in preparation.
Table 3. National management of carbapenemase-producing Enterobacteriaceae (CPE) in 39 European countries, 2013*
Countries that were uncertain about their epidemiological stages had on average 1.9 national management documents regulating surveillance and response structures. In contrast, those who were more certain about their epidemiological stages had on average 4.7 (p-value < 0.001; Wilcoxon Rank Sum Test).
The results of this online survey, performed in February 2013, show that, based on the knowledge and judgment of NEs, CPE are continuing to spread in Europe. Although most countries reported only single hospital outbreaks, the epidemiological situation has deteriorated over the past three years. Among the 31 countries that participated in both 2010 and 2013 assessments, 17 countries were upgraded to a higher epidemiological stage (Table 2*). Three countries that reported sporadic occurrence or single hospital outbreaks of CPE in 2010 are now witnessing regional or inter-regional spread, or even an endemic situation. Malta moved from having sporadic cases to an endemic situation, although by nature of its small size, the intermediate epidemiological stages have little relevance. The influx of injured refugees from Libya in 2011, is believed to have contributed to an increase in carbapenem-hydrolysing oxacillinase (OXA)-48-positive Enterobacteriaceae (M. Borg, personal communication, April 2013). In Italy, a sporadic occurrence of Verona integron-encoded metallo-beta-lactamase (VIM)-producing Enterobacteriaceae from 2008, accentuated by a single hospital outbreak, has been overtaken by the wide dissemination of KPC-positive K. pneumoniae strains to many healthcare institutions. [4-9]. The situation in Hungary has evolved in the opposite direction: in 2010, concern centred upon a single clone of KPC-2-positive K. pneumoniae that had attained regional distribution, whereas VIM-4-positive strains were only reported sporadically, but have now spread nationwide [3,10]. Overall, KPC-positive Enterobacteriaceae still have the widest distribution among CPE in Europe, but rising numbers of OXA-48-positive isolates are reported, making OXA-48 the most frequently detected carbapenemase in Belgium, France and Malta. Despite the attention that NDM has received when associated with introductions from the Indian subcontinent, the current numbers of reports by European countries are still relatively modest compared to the other carbapenemases . The United Kingdom, however, continues to report more NDM-positive isolates than most other European countries [3,12].
The NEs completed the questionnaire to the best of their knowledge, but these were subjective assessments that may have underestimated the true extent of the spread of CPE. Underdetection and underreporting were pointed out by respondents in several countries, leading to uncertainty about the true epidemiological stage (Figure). In particular, this applied to countries from which introductions into other countries have been described but where NEs could not independently assess the extent of CPE spread. Underdetection and underreporting of CPE also coincided with weaker reference laboratory infrastructures and the absence of national recommendations for submission to national reference laboratories and for reporting to health authorities, thus suggesting that the true extent of CPE occurrence in Europe is still underestimated. At the same time, countries with strict screening policies and good surveillance are more likely to report advanced epidemiological stages also affecting the comparability of the assessment.
The keys to success in preventing the establishment of CPE are, firstly, early detection through good diagnostic practices, secondly, containment of spread through patient and contact screening as well as infection control measures. An increasing number of countries have reacted and implemented measures as indicated by the increasing availability of a recommendation or guideline on infection control measures to prevent the spread of CPE . Still 17 countries surveyed lacked such guidance and the same number of countries lacked relevant guidance for submission of isolates to national reference laboratories . The results of the present report underscore the urgent need for an upgrading of laboratory standards to enable active surveillance and preventive action. To this purpose, the EuSCAPE programme aims to build a laboratory-based network for CPE detection in Europe.
The European Survey on Carbapenemase-Producing Enterobacteriaceae (EuSCAPE) working group (national experts)
Albania – Andi Koraqi; Austria – Petra Apfalter; Belgium – Youri Glupczynski; Bosnia and Herzegovia – Tatjana Marković; Bulgaria – Tanya Strateva; Croatia – Arjana Tambić Andrašević; 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 – Alkis Vatopoulos; Hungary – Ákos Tóth; 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 Mijović; The Netherlands – Henk Bijlmer; Norway – Ørjan Samuelsen; Poland – Dorota Żabicka; Portugal – Manuela Caniça; the former Yugoslav Republic of Macedonia – Ana Kaftandzieva; Romania – Maria Damian; Scotland – Camilla Wiuff; Serbia – Zora Jelesić; Slovakia – Milan Nikš; Slovenia – Mateja Pirš; Spain – Jesùs Oteo; Sweden – Christian G. Giske; Switzerland – Andrea Endimiani; Turkey – Deniz Gür; United Kingdom – Neil Woodford.
The European Survey on Carbapenemase-Producing Enterobacteriaceae (EuSCAPE) is funded by ECDC through a specific framework contract (ECDC/2012/055) following an open call for tender (OJ/25/04/2012-PROC/2012/036). Switzerland does not receive ECDC funding, but contributes to the survey using resources from the National Surveillance Program ‘ANRESIS’ (www.anresis.ch) funded by the Federal Office of Public Health.
Conflict of interest
Corinna Glasner, Barbara Albiger, Dominique Monnet, Hajo Grundmann: wrote the manuscript. Corinna Glasner, Barbara Albiger, Girbe Buist, Arjana Tambić Andrašević , Rafael Cantón, Yehuda Carmeli, Alexander W. Friedrich, Christian G. Giske, Youri Glupczynski, Marek Gniadkowski, David M. Livermore, Patrice Nordmann, Laurent Poirel, Gian Maria Rossolini, Harald Seifert, Alkiviadis Vatopoulos, Timothy Walsh, Neil Woodford, Dominique Monnet, Hajo Grundmann and the EuSCAPE working group: provided feedback, contributed with comments and reviewed the manuscript. Tjibbe Donker: provided technical assistance with the production of the maps. Corinna Glasner, Barbara Albiger, Girbe Buist, Arjana Tambić Andrašević, Rafael Cantón, Yehuda Carmeli, Alexander W. Friedrich, Christian G. Giske, Youri Glupczynski, Marek Gniadkowski, David M. Livermore, Patrice Nordmann, Laurent Poirel, Gian Maria Rossolini, Harald Seifert, Alkiviadis Vatopoulos, Timothy Walsh, Neil Woodford, Dominique L. Monnet, Hajo Grundmann: designed and reviewed the questionnaire survey. Corinna Glasner, Hajo Grundmann: supervised and coordinated the survey with the EuSCAPE working group in Europe. Corinna Glasner, Barbara Albiger, Dominique Monnet, Hajo Grundmann: performed the data analysis. The EuSCAPE working group: answered the survey and provided the country specific data.
* Authors’ correction
The following corrections were made at the request of the authors on 15 August 2013: the numbers of the tables have been corrected throughout the text and corrections have been made in Table 3 for Ireland, Kosovo, Latvia and the Netherlands. On 24 November 2014, additional amendments to Table 3 were implemented for Bulgaria, and parts of the text describing this Table were modified accordingly.
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