Central Asian and Eastern European surveillance of antimicrobial resistance: CAESAR Manual Version 2, 2015

CAESAR Manual Version 2, 2015 Central Asian and Eastern European Surveillance of Antimicrobial Resistance

Central Asian and Eastern European Surveillance of Antimicrobial Resistance CAESAR Manual Version 2, 2015 Abstract This document describes the objectives, methodology and organization of the Central Asian Eastern European Surveillance of Antimicrobial Resistance network. The document provides the steps that have to be taken by a country for participation, the steps for routine data collection, and the protocols and AMR case definitions to be used. As CAESAR is fully complementary to and compatible with the European Antimicrobial Resistance Surveillance Network at the European Center for Disease Prevention and Control, this manual is an adaptation from the EARS-Net reporting protocol (version 4, 2014)2 and the EARSS manual 2005. Keywords ANTIMICROBIAL RESISTANCE NATIONAL SURVEILLANCE NETWORKS ANTIMICROBIAL SUSCEPTIBILITY TESTING DATA COLLECTION DATA ANALYSIS Address requests about publications of the WHO Regional Office for Europe to: Publications WHO Regional Office for Europe UN City, Marmorvej 51 DK-2100 Copenhagen Ø, Denmark Alternatively, complete an online request form for documentation, health information, or for permission to quote or translate, on the Regional Office website (http://www.euro.who.int/pubrequest). © World Health Organization 2015 All rights reserved. The Regional Office for Europe of the World Health Organization welcomes requests for permission to reproduce or translate its publications, in part or in full. The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. All reasonable precautions have been taken by the World Health Organization to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either express or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for damages arising from its use. The views expressed by authors, editors, or expert groups do not necessarily represent the decisions or the stated policy of the World Health Organization. III Contents Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . V 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1.1. What is CAESAR? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1.2. Objectives for AMR surveillance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1.3. CAESAR manual and related EUCAST guidelines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 2. Organization of the CAESAR network . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 2.1. The CAESAR project group at the international level . . . . . . . . . . . . . . . . . . . . . . . . . . 5 2.2. The national networks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 2.3. Collecting and processing data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 2.4. Laboratories . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 2.5. AMR focal point and the national data manager . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 2.6. Feedback from CAESAR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 3. Steps in setting up a national network . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 3.1. Ministry of health . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 3.2. Contact the CAESAR project group . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 3.3. Appoint an AMR focal point and a national data manager . . . . . . . . . . . . . . . . . . . . . . 9 3.4. Selection of laboratories and hospitals participating in CAESAR.. . . . . . . . . . . . . . . 10 3.4.1. Synchronization of laboratories . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 3.4.2. Assignment of laboratory and hospital codes . . . . . . . . . . . . . . . . . . . . . . . . . . 10 3.4.3. Data management at the participating laboratories . . . . . . . . . . . . . . . . . . . . 10 3.4.4. Test phase laboratory data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 3.4.5. Finalization of the list of participating laboratories . . . . . . . . . . . . . . . . . . . . . 11 3.4.6. Laboratory/hospital questionnaire . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 3.4.7. Test phase data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 3.4.8. Start of regular reporting to CAESAR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 3.4.9. Contact information regarding data reporting . . . . . . . . . . . . . . . . . . . . . . . . . 12 4. AMR case definitions for data exchange . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 5. Dataset for AMR surveillance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 IV 6. Preparing national datasets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 6.1. Check for duplicate records . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 7. Data management and analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 7.1. Preparing the dataset for analysis at RIVM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 7.2. Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 8. Description of the set of variable for AMR surveillance . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 9. Denominator questionnaire . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 Annex 1. Letter of Agreement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 Annex 2. Isolate record forms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43 Isolate record form STREPTOCOCCUS PNEUMONIAE (STRPNE) . . . . . . . . . . . . . . . . . . . . . 44 Isolate record form STAPHYLOCOCCUS AUREUS (STAAUR) . . . . . . . . . . . . . . . . . . . . . . . . . 45 Isolate record form ENTEROCOCCUS FAECALIS (ENTFAE) . . . . . . . . . . . . . . . . . . . . . . . . . . 46 Isolate record form ENTEROCOCCUS FAECIUM (ENTFAI) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 Isolate record form ESCHERICHIA COLI (ESCCOL) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 Isolate record form KLEBSIELLA PNEUMONIAE (KLEPNE) . . . . . . . . . . . . . . . . . . . . . . . . . . 48 Isolate record form PSEUDOMONAS AERUGINOSA (PSEAER) . . . . . . . . . . . . . . . . . . . . . . . 49 Isolate record form ACINETOBACTER SPP (ACISPP) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 Annex 3. List of EARS-net/CAESAR pathogens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 Annex 4. List of S. pneumoniae serotypes (Kauffman-Lund scheme) . . . . . . . . . . . . . . . . . . . 55 VAbbreviations AMR Antimicrobial resistance AST Antimicrobial susceptibility test CAESAR Central Asian and Eastern European Surveillance of Antimicrobial Resistance CLSI Clinical and Laboratory Standards Institute CSF Cerebrospinal fluid EARS-Net European Antimicrobial Resistance Surveillance Network EARSS European Antimicrobial Resistance Surveillance System ECDC European Centre for Disease Prevention and Control ESBL Extended-spectrum beta lactamase ESCMID European Society of Clinical Microbiology and Infectious Diseases ESGARS ESCMID Study Group for Antimicrobial Resistance Surveillance EUCAST European Committee on Antimicrobial Susceptibility Testing FTP File transfer protocol ICM Intersectoral coordination mechanism ICU Intensive care unit MIC Minimal inhibitory concentration MRSA Methicillin-resistant Staphylococcus aureus MSSA Methicillin-susceptible Staphylococcus aureus PNSP Penicillin nonsusceptible Streptococcus pneumoniae RIVM National Institute for Public Health and the Environment (in the Netherlands) RIVM-Cib Centre for Infectious Disease Control of RIVM S/I/R Susceptible/Intermediate/Resistant VRE Vancomycin-resistant enterococci WHO World Health Organization WHONET WHO microbiology laboratory database software VI CHAPTER 1 1Introduction 1.1. What is CAESAR? CAESAR stands for Central Asian and Eastern European Surveillance of Antimicrobial Resistance. The CAESAR network is a joint initiative of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), the National Institute for Public Health and the Environment (RIVM) in the Netherlands and the World Health Organization (WHO) Regional Office for Europe, to survey, contain and prevent emergence and spread of antibiotic resistance in a selected number of countries in the WHO European Region. Antimicrobial resistance (AMR) and especially resistance to antibiotics is an increasing global public health problem. The WHO European Region is no exception, and resistance of some pathogens now reaches over 50% in some countries and new resistance mechanisms are emerging and spreading rapidly. Surveillance of antibiotic resistance is undertaken by all 28 countries of the European Union, as well as in Norway, Iceland and Liechtenstein under the EARS-Net (European Antimicrobial Resistance Surveillance Network) system of the European Commission coordinated by the European Centre for Disease Prevention and Control (ECDC). This system is a well-developed and accepted surveillance network to report and survey trends in antibiotic resistance. However, the emergence and spread of antibiotic resistance does not acknowledge borders. Therefore, to safeguard public health in Europe it is of paramount importance to develop a harmonized and coordinated surveillance network in all 53 countries of the WHO European Region. The aim of the CAESAR network is to gradually set up a network of national surveillance systems of antibiotic resistance in all countries of the WHO European Region that are not part of, or affiliated with, EARS-Net. In order to enable compilation and comparison of data in the whole European Region, the methodology of EARS-Net will be used in close collaboration with ECDC. In the future, this approach will enable joined reports of antibiotic resistance for all 53 countries based on the same standards and methodologies. The CAESAR network is a fundamental step in the implementation of the European strategic action plan on antibiotic resistance that was adopted by the WHO Regional Committee for Europe in Baku, Azerbaijan in September 20111. CAESAR meets the first two of the seven strategic objectives of the European strategic action plan on antibiotic resistance: 1) promoting national coordination and 2) strengthening surveillance of antibiotic resistance. In addition, CAESAR is a good starting point in achieving the other objectives: 3) promoting rational use of antibiotics, including surveillance of antibiotic consumption; 4) improving infection control and stewardship of antibiotic use in health care settings; 5) promoting surveillance, prevention and control of antibiotic resistance in the food chain; 6) promoting research and innovation on new antibiotics; and 7) improving awareness of antibiotic use and the risk of increasing resistance. 1.2. Objectives for AMR surveillance The CAESAR strategy for AMR surveillance is in line with the one adopted by the former European Antimicrobial Resistance Surveillance System (EARSS) and EARS-Net. Therefore, the approach is to maintain a comprehensive surveillance system that links national networks and provides comparable and validated data on the prevalence and trends in AMR of a core group of invasive bacteria. The specific objectives are as follows: • collect comparable and validated AMR data; • analyse trends over time; C H A PT ER 1 1 http://www.euro.who.int/__data/assets/pdf_file/0008/147734/wd14E_AntibioticResistance_111380.pdf 2• provide timely AMR data that constitute a basis for policy decisions; • encourage the implementation, maintenance and improvement of national AMR surveillance programmes; • support national systems in their efforts to improve diagnostic accuracy and quality at every level of the surveillance chain; • link AMR data to factors influencing the emergence and spread of AMR, such as antibiotic use data; • link the European scientific and professional community to exchange experience and expertise; and • initiate, foster and complement scientific research in Europe in the field of AMR. 1.3. CAESAR manual and related EUCAST guidelines This document describes the objectives, methodology and organization of CAESAR, the steps that have to be taken by a country for participation, the steps for routine data collection and the protocols and AMR case definitions to be used. As CAESAR is fully complementary to and compatible with EARS-Net, this manual is an adaptation from the EARS-Net reporting protocol (version 4, 2014)2 and the EARSS manual 2005. In addition to the CAESAR manual, the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines for detection of resistance mechanisms and specific resistances of clinical and/or epidemiological importance is available on the EUCAST website3. The guideline includes definitions of the mechanisms of resistance, an outline description of the recommended methods of detection, and references that detail descriptions of the methods of detection for: 1. carbapenemase-producing Enterobacteriaceae 2. extended-spectrum β-lactamase-producing Enterobacteriaceae 3. acquired AmpC β-lactamase-producing Enterobacteriaceae 4. methicillin-resistant Staphylococcus aureus (MRSA) 5. glycopeptide nonsusceptible S. aureus 6. vancomycin-resistant enterococci (VRE) 7. penicillin nonsusceptible Streptococcus pneumoniae (PNSP). 2 http://ecdc.europa.eu/en/activities/surveillance/EARS-Net/Documents/2015-EARS-Net-reporting-protocol.pdf 3 http://www.eucast.org/resistance_mechanisms/ 3C H A PT ER 1 CHAPTER 2 5Organization of the CAESAR network 2.1. The CAESAR project group at the international level The CAESAR project group consists of three representatives from WHO Regional Office for Europe, and two from the ESCMID Study Group for Antimicrobial Resistance Surveillance (ESGARS-ESCMID) and WHO Collaborating Centre for AMR Epidemiology and Surveillance at the Centre for Infectious Disease Control (Clb) of RIVM (RIVM-CIb); see Chapter 3.2 for contact details: • Dr Danilo Lo Fo Wong (WHO Regional Office for Europe) • Dr Nienke van de Sande – Bruinsma (WHO Regional Office for Europe) • Dr Saskia Nahrgang (WHO Regional Office for Europe) • Dr Christian Giske (ESGARS-ESCMID) • Dr Robert Skov (ESGARS-ESCMID) • Jos Monen, MSc (RIVM-CIb) • Dr Tjalling Leenstra (RIVM-CIb) C H A PT ER 2 Figure 1. CAESAR organization structure WP1 – Country situation analysis; WP2 – Laboratory capacity building; WP3 – Set up surveillance network on the national level; WP4 – Collect AMR surveillance data of the participating countries in the CAESAR database platform; WP5 – Project output Lab 1 Lab 2 Lab 3 AMR focal point and data manager at country level CAESAR project group at international level Pools of experts WP1 t/m WP5Steering committee ECDC WHO & WHO Regional O‚ce for Europe ESCMID RIVM 62.2. The national networks Each participating country needs to appoint an AMR focal point and a national data manager. The main task of the AMR focal point is to connect the CAESAR-specific activities of the participating laboratories and ensure that the laboratories generate their antimicrobial susceptibility test (AST) data according to CAESAR protocols, as published in this manual. The main task of the national data manager is to collect, approve and forward resistance data every quarter or year and to assist the AMR focal point. Often the data requested by the CAESAR network is already collected via the national surveillance system that is already in place in a country. Alternatively, a national surveillance network will need to be developed using CAESAR methodology as described in this manual. The role of the AMR focal point is to coordinate the national surveillance system on AMR. In this role, they encourage the participation of laboratories and hospitals such that a good representation of the population is achieved. Preferably, coverage should exceed 20% of the national population, and health care systems should be represented with respect to the mix of academic/tertiary care hospitals and general hospitals. Furthermore, geographic distribution should be even and include urban and rural catchment areas. 2.3. Collecting and processing data CAESAR data collection includes routinely collected susceptibility test results of invasive isolates and background information about patients. Laboratories are asked to report the first isolate from blood per species or cerebrospinal fluid per patient per year. According to the specifications of the CAESAR exchange format4 (see Chapter 5) the system requires the following: laboratory code, isolate sample number, isolate source, date of sample collection, sex, month and year of birth, hospital code, hospital department, origin of patient, level of care (ambulant, hospitalized, etc.), bacterial species and AST results as specified in the protocols. Furthermore, optional data are collected including susceptibility data for other antibiotics and the serotype of the reported S. pneumoniae strains. In order for CAESAR to provide a representative description of the antimicrobial susceptibility in the country, all patients presenting with signs of a bloodstream infection (systemic inflammatory response syndrome) or meningitis should be sampled, if possible, prior to initiation of antimicrobial therapy. Including only special patient categories (e.g. only patients in intensive care units [ICU] or tertiary care institutions), patients with chronic or recurring infections, or with relapses or treatment failure will overestimate the resistance proportion because these patients were subjected to selective pressure of antimicrobials. 2.4. Laboratories Participating laboratories can opt for one of two methods of data submission: electronically (WHONET, Excel, LIS) or on conventional isolate record forms (paper and Microsoft-Excel-based electronic data entry forms). CAESAR recommends laboratories to use WHONET, a free Windows-based database software that is downloadable from the WHO website5. This software was developed for the management and analysis of microbiology laboratory data with a special focus on collection and analysis of AST results, and includes an automated export function dedicated to the EARS-Net/CAESAR data format. Isolate record forms are now available as Microsoft-Excel-based data entry forms (see Annex 2), enabling the electronic capture of CAESAR data at local laboratory level without the need for a dedicated laboratory information system. Data are stored in .xls spreadsheet format and are readily exported in the required CAESAR data format. Additionally, the data entry form automatically checks for completeness, and it ensures sensible data. The data form can be configured to any language. The required translation can 4 In concordance with the EARS-Net exchange format 5 http://www.who.int/drugresistance/whonetsoftware/en/ 7be made by any user, without the need for programming skills. The data entry form and instructions for use can be obtained from the international data manager by email (caesar@rivm.nl). Laboratories are asked to collect and forward all AST data specified by the standard CAESAR protocols described in this manual to the national data manager on a quarterly basis. Before submission, laboratories are asked to check their data for: • adherence to CAESAR protocol; • microbiological consistency/plausibility; and • consistency with AST methods and clinical S/I/R breakpoints according to the respective guideline issued by an appropriate board or committee (EUCAST6 or the Clinical and Laboratory Standards Institute [CLSI]7). 2.5. AMR focal point and the national data manager At national level, data are processed by the national data manager in consultation with the AMR focal point in a stepwise procedure. • Data are recorded from all participating laboratories (completeness). • Manual data entries are made in cases in which paper isolate records forms are used. • Data are merged from all participating laboratories into one single file. • Duplicate reports are removed. Only primary isolates per patient per quarter or year are included in the database. Duplicate records per patient are ignored. • Data are converted into EARS-Net exchange format. • Data are approved by the AMR focal point who checks for adherence to CAESAR protocol, microbiological consistency and whether S/I/R interpretations are in agreement with the minimal inhibitory concentrations or disk inhibition zones (mm) reported. • Data are transferred to the international data manager on a quarterly or yearly basis. 2.6. Feedback from CAESAR Accurate and timely feedback is essential for surveillance systems. Once made available to CAESAR, data are analysed and returned as a standard feedback report to the AMR focal point. This feedback contains information on pathogens with important (MRSA, PNSP and VRE) and unusual resistance patterns, and contains information on the validity and completeness of the data. Subsequently, the AMR focal point is asked to confirm the correctness of the results. With this approval, the data will be added to the CAESAR database. The data from the CAESAR database are used to prepare annual reports, newsletters and publications that are disseminated to the participants, policy makers and to a broader public. In addition, a WHO website will be developed for display of the data. C H A PT ER 2 6 http://www.eucast.org/ 7 http://www.clsi.org/ 8CHAPTER 3 9Steps in setting up a national network This chapter describes the steps that are needed in setting up the national coordination and a network of laboratories to enable national AMR surveillance according to CAESAR methodology. 3.1. Ministry of health The main objective of CAESAR is to supply reliable information on AMR in participating countries. One of the main parties interested in this information is the national ministry of health. Therefore, it is essential to involve the national ministry of health when setting up a national surveillance network on AMR and to gain their support. 3.2. Contact the CAESAR project group For more information and support in setting up a national network please contact Dr Danilo Lo Fo Wong or Dr Nienke van de Sande-Bruinsma at the WHO Regional Office for Europe, Copenhagen, Denmark. 3.3. Appoint an AMR focal point and a national data manager In each participating country an AMR focal point is appointed by the ministry of health. The AMR focal point has several responsibilities, including the coordination of AMR surveillance in the country and appointing a national data manager. The AMR focal point also has other responsibilities, as described in the European strategic action plan on antibiotic resistance. One is to set up and/or sustain an intersectoral coordination mechanism (ICM) for AMR (e.g. taskforce, steering committee, board or council). The ICM should encompass representatives from the relevant stakeholders for AMR (e.g. ministry of health, ministry of agriculture, national reference laboratories, public health institutes, national medicines agency, academia, nongovernmental organizations and the private sector). Another responsibility is to develop or review a national AMR action plan (including objectives, policies, surveillance and control). Through the C H A PT ER 3 Dr Danilo Lo Fo Wong, Senior Adviser AMR Communicable Diseases, Health Security, and Environment WHO Regional Office for Europe Marmorvej 51 DK-2100 Copenhagen Denmark Tel: +45 45 33 66 12 Mob: +45 51 53 96 16 Email: dlo@euro.who.int Dr Nienke van de Sande-Bruinsma, Technical officer AMR Communicable Diseases, Health Security, and Environment WHO Regional Office for Europe Marmorvej 51 DK-2100 Copenhagen Denmark Tel: +45 45 33 68 27 Mob: +45 24 52 30 03 Email: nvs@euro.who.int 10 ICM, the national AMR focal point ensures regular data collection and information sharing and facilitates effective communication and coordination between its members and their constituents. 3.4. Selection of laboratories and hospitals participating in CAESAR Results reported to CAESAR must be based on routine clinical samples. To base the data collection on strains sent to specialist laboratories for reference purposes (reference centres) would severely bias the results. If a participating laboratory asks the reference laboratory to conduct an MIC, for example of vancomycin for an MRSA strain, then these MICs should be included in the report from this participating laboratory. 3.4.1. Synchronization of laboratories Key staff members from laboratories expressing an interest in national surveillance are invited to a meeting with the national management team by the AMR focal point in order to explain the aims of the CAESAR network and what they will be expected to do. PowerPoint presentations are available from the CAESAR project group or a member of the CAESAR project group could be invited to attend the meeting. 3.4.2. Assignment of laboratory and hospital codes The national management team assigns laboratory and hospital codes to the (potential) CAESAR participants. Laboratory codes consist of the first two letters of the country code (e.g. RU for Russian Federation) plus three digits (e.g. 001), resulting in codes such as RU001, RU002 and RU003. Hospital codes preferably should consist of four characters: the three characters of the laboratory plus one letter (e.g. 001A). 3.4.3. Data management at the participating laboratories For the participating laboratories, there are several ways to report data to the national data manager. • If WHONET is used at laboratory level, data export is simple, as exporting EARS-Net files is a standard feature of WHONET, and CAESAR is compatible with EARS-Net (TESSy). To create a CAESAR export file, choose the option to export TESSy(CSV) format . The exported CSV file can be sent to CAESAR. It is important that WHONET is set up properly, with the exact tests as used in the laboratory, and choosing the breakpoints according to the standard used. As with EARS-Net, the preferred standard for laboratories participating in CAESAR is EUCAST (alternatively CLSI). If another standard is used, efforts should be made to calibrate results to EUCAST. If configured this way, interpretation is carried out automatically by WHONET according to these breakpoints. This prevents discrepancies between zone diameter or MIC and the interpretation. • If the laboratory uses a laboratory information system based on a database, there are several possibilities. • Laboratory information system export functionality (query language) can be used. • In order to export CAESAR files directly, a skilled programmer is needed to make the export query. Difficulties can arise because a numeric identifier needs to be derived from the patient identifier. In addition, the date format needs to adhere to the CAESAR specification. • If it is too difficult to produce CAESAR files directly, the program BACLINK can be used. This program is bundled with WHONET and can be used to import any export format into 11 WHONET. No special programming skills are needed to configure BACLINK. When data are imported into WHONET, CAESAR export can be performed as described above. • For laboratories not using a laboratory information system or WHONET, or small laboratories with few isolates, the CAESAR team developed an Excel file with forms that can be used to enter data manually. The forms generate the correct codes, and automatically check for completeness of the data. The data form can be configured for each country or each laboratory, meaning that only the antibiotics that are tested will be visible. Moreover, the forms can be translated into any language. The required configuration and translation can be made by any user, without the need of programming skills. To receive a copy of this Excel tool or WHONET please email to the international data manager (Caesar@rivm.nl) • For (small) laboratories not having access to computers, paper forms can be used. The national data manager can use the Excel tool to enter the data from the paper forms. 3.4.4. Test phase laboratory data If the national data manager receives data from the individual laboratories on paper (isolate record forms), manual data entry into the electronic database is required. Regardless, if the data arrive in electronic format or on paper, they always need to be checked for consistency with CAESAR protocols and for microbiological plausibility. • Do the AST data reported follow the CAESAR protocol? For example, are MRSA strains reported with a vancomycin MIC? • Do the data make sense? For example, an ampicillin-susceptible Escherichia coli strain with a ceftriaxone MIC of 15 probably reflects an error in data entry or laboratory practice. • Are the S/I/R interpretations consistent with the breakpoints used by the laboratory? To check this, the national data manager needs to know what kind of guidelines the individual laboratories are using (preferably EUCAST, or CLSI). • The data also need to be checked for adherence with the CAESAR data exchange format. 3.4.5. Finalization of the list of participating laboratories When both the laboratories and the AMR focal point have agreed on the participation in CAESAR, a letter of agreement may be signed (Annex 1). The AMR focal point should ensure that the selection of laboratories participating in CAESAR provides a representative sample of the national population. If it is suspected that this is not the case, the AMR focal point should attempt to recruit additional laboratories to increase the representativeness of the sample. 3.4.6. Laboratory/hospital questionnaire After the finalization of the laboratory list, the AMR focal point needs to ensure that laboratories provide certain details on the laboratory and hospital characteristics and population denominators using the questionnaire (Chapter 9). If one laboratory serves, for example, two hospitals, then two laboratory/ hospital questionnaires need to be filled out (the laboratory information will be repeated in the second questionnaire). More detailed information on the questionnaire is given in Chapter 9. C H A PT ER 3 12 3.4.7. Test phase data National data managers are encouraged to submit a first complete (merged) data set to CAESAR that can then be checked for consistency and adherence with the EARS-Net data exchange format. At this point, the international data manager of CAESAR and the national data manager will communicate frequently to improve the quality of the data, if necessary. 3.4.8. Start of regular reporting to CAESAR Full data reporting to CAESAR should preferably start with the full (all participating laboratories) data set of one entire quarter, via email or secure FTP account. Data can be sent on a quarterly basis, but the ultimate deadline for sending in data of the whole previous year is June. 3.4.9. Contact information regarding data reporting Jos Monen, Expert on International Data Management Epidemiology and Surveillance Centre for Infectious Diseases Control National Institute for Public Health and the Environment (RIVM) WHO Collaborating Centre for Antimicrobial Resistance Epidemiology and Surveillance Antonie van Leeuwenhoeklaan 9 3721 MA Bilthoven, The Netherlands Email: caesar@rivm.nl Phone: +31 (0)30 274 3956 13 C H A PT ER 3 14 CHAPTER 4 15 AMR case definitions for data exchange Given the typology of data for AMR surveillance (which refers to laboratory isolates rather than to cases of disease), the following case definition has been implemented. • The bacterial species under surveillance8 are S. pneumoniae (STRPNE), S. aureus (STAAUR), Enterococcus faecalis (ENCFAE), E. faecium (ENCFAI), E. coli (ESCCOL), Klebsiella pneumoniae (KLEPNE), Pseudomonas aeruginosa (PSEAER) and Acinetobacter spp. (ACISPP). • All isolates from blood (STRPNE, STAAUR, ENCFAE, ENCFAI, ESCCOL, KLEPNE, PSEAER, ACISPP) and/or cerebrospinal fluid (STRPNE, ESCCOL, KLEPNE, PSEAER, ACISPP), for which a susceptibility test has been performed, have to be included. • Duplicates from the same patients are ignored, only the first by date of sample collection and isolate source per species is taken into account. The bug/source/drug combinations to be reported are listed in table 1. If records referring to additional combinations are uploaded, they will be collected but not be reported in the regular reports. • The minimal panel recommended by EUCAST and ESGARS-ESCMID for CAESAR reporting has been included as a separate column. • Additionally, a column has been added regarding antimicrobials for which EUCAST has specific recommendations in terms of detection of resistance mechanisms9. • In accordance with the EARS-Net reporting protocol, a number of additional antimicrobial agents have been added to the list of agents for which it is possible to report AST results (marked with an * in Table 1 below). C H A PT ER 4 8 In the initial implementation phase of CAESAR, the number of bacterial species under surveillance can be limited to fewer. 9 http://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Consultation/EUCAST_guidelines_detection_of_resistance_mechanisms_121222.pdf Table 1. The pathogen, source and antibiotic combinations to be reported to CAESAR, including the minimal panel for reporting and available guidelines for detection of resistance mechanisms according to EUCAST Pathogen Source/specimen Antibiotic EUCAST/ESGARS minimum panel for CAESAR reporting EUCAST guidelines for detection of resistance mechanisms Streptococcus pneumoniae (STRPNE) Blood (BLOOD); cerebrospinal fluid (CSF) Penicillin (PEN) Oxacillin (OXA) Ceftriaxone (CRO) OR Cefotaxime (CTX) Erythromycin (ERY) OR Clarithromycin (CLR) OR Azithromycin (AZM) Norfloxacin (NOR) OR Levofloxacin (LVX) OR Moxifloxacin (MFX) Penicillin Oxacillin (screen) Erythromycin Norfloxacin (screen) OR Levofloxacin OR Moxifloxacin Penicillin 16 Pathogen Source/specimen Antibiotic EUCAST/ESGARS minimum panel for CAESAR reporting EUCAST guidelines for detection of resistance mechanisms Staphylococcus aureus (STAAUR) Blood (BLOOD) Oxacillin (OXA) OR Cefoxitin (FOX) Norfloxacin (NOR) OR Ciprofloxacin (CIP) OR Ofloxacin (OFX) OR Levofloxacin (LVX) Rifampicin (RIF) Linezolid (LNZ) Vancomycin (VAN)* Daptomycin (DAP)* Cefoxitin (disk screen) Vancomycin Cefoxitin (disk screen) Vancomycin Enterococcus faecalis (ENCFAE) Blood (BLOOD) Ampicillin (AMP) OR Amoxicillin (AMX) Gentamicin-High (GEH) Vancomycin (VAN) Teicoplanin (TEC) Linezolid (LNZ) Ampicillin Gentamicin-High Vancomycin Vancomycin Enterococcus faecium (ENCFAI) Blood (BLOOD) Ampicillin (AMP) OR Amoxicillin (AMX) Gentamicin-High (GEH) Vancomycin (VAN) Teicoplanin (TEC) Linezolid (LNZ) Ampicillin Gentamicin-High Vancomycin Vancomycin Escherichia coli (ESCCOL) and Klebsiella pneumoniae (KLEPNE) Blood (BLOOD); cerebrospinal fluid (CSF) Ampicillin (AMP) OR Amoxicillin (AMX) Piperacillin-tazobactam (TZP) OR Amoxicillin-clavulanic acid (AMC)* Gentamicin (GEN) OR Tobramycin (TOB) OR Amikacin (AMK) Netilmicin (NET)* Ceftriaxone (CRO) OR Cefotaxime (CTX) OR Ceftazidime (CAZ) Cefepime (FEP)* Ciprofloxacin (CIP) OR Ofloxacin (OFX) OR Levofloxacin (LVX) OR Moxifloxacin (MFX)* Meropenem (MEM) OR Imipenem (IPM) OR Ertapenem (ETP) * Tigecycline (TGC)* Colistin (COL)* Polymyxin B (POL)* Piperacillin-tazobactam OR Amoxicillin-clavulanic acid Gentamicin OR Tobramycin OR Amikacin Ceftriaxone OR Cefotaxime OR Ceftazidime Ciprofloxacin OR Ofloxacin OR Levofloxacin Meropenem OR Imipenem OR Ertapenem Ceftriaxone Cefotaxime Ceftazidime Meropenem Imipenem Ertapenem Pseudomonas aeruginosa (PSEAER) Blood (BLOOD); cerebrospinal fluid (CSF) Piperacillin (PIP) Piperacillin/tazobactam (TZP) Ceftazidime (CAZ) Cefipime (FEP)* Ciprofloxacin (CIP) OR Levofloxacin (LVX) Gentamicin (GEN) OR Tobramycin (TOB) OR Amikacin (AMK) Netilmicin (NET)* Imipenem (IPM) OR Meropenem (MEM) Piperacillin/tazobactam Ceftazidime Cefipime Ciprofloxacin OR Levofloxacin Gentamicin OR Tobramycin OR Amikacin Imipenem OR Meropenem 17 C H A PT ER 4 Pathogen Source/specimen Antibiotic EUCAST/ESGARS minimum panel for CAESAR reporting EUCAST guidelines for detection of resistance mechanisms Acinetobacter spp. (ACISPP) Blood (BLOOD); cerebrospinal fluid (CSF) Ciprofloxacin (CIP) OR Levofloxacin (LVX) Gentamicin (GEN) OR Tobramycin (TOB) OR Amikacin (AMK)* Netimicin (NET)* Imipenem (IPM) OR Meropenem (MEM) Colistin (COL)* Polymyxin B (POL)* Ciprofloxacin OR Levofloxacin Gentamicin OR Tobramycin OR Amikacin Imipenem OR Meropenem * In accordance with the EARS-Net reporting protocol, a number of additional antimicrobial agents have been added to the list of agents for which it is possible to report AST results. 18 CHAPTER 5 19 Dataset for AMR surveillance The set of variables for isolate-based AMR reporting consists of eight technical variables and 29 epidemiological variables, which are further classified into variables at patient/isolate level and variables at AMR test level. The first level includes data referring to the isolate, which are repeated in all records reporting the AST performed for that isolate (see table 2). The variables are described in more detail, including the validation rules, in Chapter 6. C H A PT ER 5 Table 2. Set of variables for isolate-based AMR reporting to CAESAR Variable name Mandatory Explanation Technical variables 1. RecordId 2. RecordType 3. RecordTypeVersion 4. Subject 5. DataSource 6. ReportingCountry 7. DateUsedForStatistics 8. Status Yes Yes Yes Yes Yes Yes Unique identifier (primary key) Fixed: AMRTEST Version number of the variable set (now 2) Fixed: AMR Code for local surveillance system Country code Date of sample collection New/update or delete Epidemiological variables at isolate level 9. LaboratoryCode 10. Specimen 11. PatientCounter 12. Gender 13. Age 14. IsolateId 15. HospitalId 16. PatientType 17. HospitalUnitType 18. Pathogen 19. DateOfHospitalisation 20. ResultPCRmec 21. ResultPbp2aAggl 22. Serotype 23. ESBL 24. ResultCarbapenemases Yes Yes Yes Yes Laboratory code: two letter country code + three digits lab no. Material: BLOOD or CSF Anonymized patient ID, must be numeric Gender of the patient M/F/O/UNK Age of the patient in years Isolate sample identifier Hospital code, recommended format lab no. + one letter Origin of patient: INPAT/OUTPAT/O/UNK Hospital department (see Annex 3) Pathogen code (see Annex 3) Date of admission, YYYY-MM-DD PCR mec-gene: POS/NEG/UNK PBP2a-agglutination: POS/NEG/UNK Serotype coded according to the Danish system ESBL present: POS/NEG/UNK Carbapenase detected : POS/NEG/UNK Epidemiological variables at AMR test level 25. Antibiotic 26. SIR 27. ResultZoneSign 28. ResultZoneValue 29. ResultZoneSIR 30. ResultMICSign 31. ResultMICValue 32. ResultMICSIR 33. ResultEtestSign 34. ResultEtestValue 35. ResultEtestSIR 36. DiskLoad 37. ReferenceGuidelinesSIR Yes Yes Antibiotic code (see Annex 4) Interpretation of susceptibility: S/I/R Sign used in the zone diameter (> < =) Zone value (mm) Interpretation of susceptibility from the zone: S/I/R Sign used in the MIC (> < =) MIC (mg/l) Interpretation of susceptibility from the MIC: S/I/R Sign used in the MIC from a gradient strip test (> < =) MIC value from gradient strip test (mg/l) Interpretation of susceptibility from the gradient strip test: S/I/R Disk load (text) The used guideline (CLSI/EUCAST/NAT/O) 20 CHAPTER 6 21 Preparing national datasets This chapter for AMR data submission describes the dataset structure and the variable coding. Questions regarding coding, upload of data, etc. should be directed to the international data manager Jos Monen (email: caesar@rivm.nl; phone: +31 (0)30 274 3956). If the data collection at laboratory level has been performed manually by filling in isolate record forms (Annex 2), the national data manager should create the fields “Age” and “PatientCounter” starting from the available information in the paper forms (“Year of birth” and “Patient ID/Code”). It is possible to generate a number from an ID in a reproducible way by means of a “hash function”. The international data manager can provide tools to produce the patient counter. If data are read into WHONET all of this is done automatically. 6.1. Check for duplicate records Before the national data manager sends the data to RIVM, they have to revise the laboratory data and check for duplicates (records with the same RecordID). If there are duplicates they should be eliminated by merging/selecting records. Recommendations for merging and selecting records are shown below. • The recommended format of the RecordID is the combination of the following fields: ReportingCountry; LaboratoryCode; PatientCounter; Pathogen; Specimen; Antibiotic; DateUsedForStatistics. • The first proposed step to deal with this problem is to identify the multiple isolates within the same day (using the field “IsolateId” when available) and select the first one per day (DateUsedForStatistics). • If there are still duplicates after the first step, the further merging/selection of records should be carried out according to the recommended method, which is summarized in examples 1, 2 and 3. • The two records above refer to the same patient and the same bug/drug combination from the same source (blood) on the same day. • To avoid this unsuccessful outcome, it is possible to merge the reported data in one row. • For the final interpretation, the presence or absence of mecA or mecC will determine the susceptibility reporting (SIR). C H A PT ER 6 Example 1 – Duplicates: same bug/drug combination but different microbiological tests Pathogen Antibiotic SIR ResultZoneSIR ResultMICValue ResultMICSIR STAAUR STAAUR FOX FOX R S R 1 S Pathogen Antibiotic SIR ResultZoneSIR ResultMICValue ResultMICSIR STAAUR FOX S R 1 Pending PCR 22 Example 2 – Duplicates: same drug/bug combination, same test, different SIR results Pathogen Antibiotic SIR ResultZoneSIR ResultMICValue ResultMICSIR STAAUR STAAUR FOX FOX R S R S 8 1 R S Example 3 – Duplicates: same drug/bug combination, same test, same SIR results Pathogen Antibiotic SIR ResultZoneSIR ResultMICValue ResultMICSIR STAAUR STAAUR FOX FOX S S S S 1 1 S S Select the first in this order R→I→S (therefore, the most resistant is selected). This is a rare occurrence and this rule is implemented to have a standard algorithm for filtering the duplicates. If the records have the same SIR result (true duplicates) just select one of them, taking into account the completeness of the other variables. 23 C H A PT ER 6 24 CHAPTER 7 25 Data management and analysis After data uploading, RIVM will provide a validation/feedback report that should be assessed by the AMR focal point and data manager before approval. The report shows summary statistics of the data from the uploaded batch. The analysis outputs are obtained using the same methodology that is used for the annual reports. 7.1. Preparing the dataset for analysis at RIVM At RIVM, the international data manager will upload the country dataset into the database platform. During the upload, a quality control will be performed and remaining duplicate isolates will be selected out, and the following steps will be performed: • for each record, and each pathogen/antibiotic line, mandatory fields will be checked; • if mandatory fields are missing, the line is not included; • the pathogen/antibiotic records are combined into one record per isolate; • only the first isolates per pathogen per patient per year is kept, the others are ignored; and • the validation/feedback report will be produced and sent back to the AMR focal point and data manager for data control and confirmation. 7.2. Analysis The proportion of resistance is often calculated considering an antibiotic group (instead of a single antibiotic), and other specifications are needed to perform the analysis. The groups often but not always represent an antibiotic class. An example of an antibiotic group is the third-generation cephalosporins for E. coli (ESCCOL). This antibiotic group includes three antibiotics: ceftriaxone (CRO), cefotaxime (CTX) and ceftazidime (CAZ). The full set of bug/antibiotic-group combinations under surveillance is displayed in table 3). C H A PT ER 7 26 Table 3. Pathogens and antibiotic-group combinations under surveillance Pathogen Antibiotics in the group Group name (results to be reported) ENCFAE/ENCFAI AMX, AMP Aminopenicillins (I+R) ENCFAE/ENCFAI GEH High-level gentamicin (R) ENCFAE/ENCFAI VAN Vancomycin (R) ENCFAE/ENCFAI TEC Teicoplanin (R) ENCFAE/ENCFAI LNZ Linezolid (I+R) ESCCOL AMX, AMP Aminopenicillins (R) ESCCOL/KLEPNE AMC, TZP Aminopenicillin + β-lactamase inhib. (R; I+R) ESCCOL/KLEPNE CTX, CRO, CAZ 3rd gen. cephalosporins (R; I+R) ESCCOL/KLEPNE AMK, GEN, TOB, NET Aminoglycosides (R) ESCCOL/KLEPNE CIP, OFX, LVX, MFX Fluoroquinolones (R; I+R) ESCCOL/KLEPNE IPM, MEM, ERT Carbapenems (R; I+R) ESCCOL/KLEPNE COL, POL Polymyxins (R) ESCCOL/KLEPNE TGC Glycylcyclines (R) PSEAER PIP, TZP Piperacillin ± tazobactam (R) PSEAER CAZ Ceftazidime (R) PSEAER/ACISPP GEN, TOB, AMK, NET Aminoglycosides (R) PSEAER/ACISPP CIP, LVX Fluoroquinolones (R) PSEAER/ACISPP IPM, MEM Carbapenems (R; I+R) PSEAER/ACISPP COL, POL Polymyxins (R) STAAUR FOX MRSA (R) STAAUR CIP, OFX, LVX, NOR Fluoroquinolones (R) STAAUR RIF Rifampin (R) STAAUR LNZ Linezolid (R) STAAUR VAN Vancomycin (R) STAAUR DAP Daptomycin (R) STRPNE PEN, OXA Penicillins (R; I+R) STRPNE ERY, CLR, AZM Macrolides (R; I+R) STRPNE CTX, CRO 3rd gen. cephalosporins (R; I+R) STRPNE LVX, NOR, MFX Fluoroquinolones (R) 27 C H A PT ER 7 General rule to calculate the proportion of resistance If two or more antibiotics (records) are reported for the same bug/antibiotic group combination, count only one of them; the choice must accord with the final interpretations of the susceptibility test (field=SIR; priority sequence R→I→S). i.e. the most resistant result is used for group-resistance. Specific rule for S. pneumoniae and nonsusceptibility to penicillin The antibiotics considered for MRSA are penicillin (PEN) and oxacillin (OXA). If both are reported, give priority to penicillin. Specific rule to define MRSA The antibiotic considered for this resistance is cefoxitin (FOX). Other tests (equivalents) are also considered as confirmation tests: PCR mecA or PBP2a detection. Hierarchical levels to assess MRSA are as follows: 1) confirmation test (PCR mecA and/or PBP2a); and 2) cefoxitin (MIC or disc diffusion). The definition of MRSA is based on the following criteria: 1) if at least one between ResultPCRmec and ResultPbp2aAggl is positive then MRSA; 2) if at least one between ResultPCRmec and ResultPbp2aAggl is negative and the other one is not positive then MSSA (methicillin-susceptible S. aureus); and 3) if both ResultPCRmec and ResultPbp2aAggl are missing then consider SIR to define susceptibility (if SIR=S then MSSA; if SIR=I or R then MRSA). Future rules to perform the resistance trend analysis The temporal trends of AMR by country are calculated and reported in the final annual report. The statistical significance of trends is assessed by the Cochrane Armitage test. Countries reporting less than 20 isolates per year or providing data for less than 3 years within the considered period are not included in the analysis. A sensitivity analysis, considering all laboratories or only those reporting for the full period, is carried out to exclude bias in assessing the significance of the trends. Web application and outputs On the WHO CAESAR web page10, outputs of the validated and approved data including European maps, bar charts and tables will become available in the future. These outputs will be available as soon as data are stored in the RIVM data warehouse (shortly after data approval). A country-specific and laboratory-specific summary report providing detailed results for the country referring to the bug/drug combinations under surveillance will be available to the user. 10 http://www.euro.who.int/en/health-topics/disease-prevention/antimicrobial-resistance/antimicrobial-resistance/central-asian-and-eastern- european-surveillance-of-antimicrobial-resistance-caesar 28 CHAPTER 8 29 Description of the set of variables for AMR surveillance C H A PT ER 8 Technical variables VariableName Description Required (what happens if not submitted) Data type 1 – RecordID Unique anonymized identifier for each record within and across the national surveillance system and subject – MS selected and generated. Recommended format: “[ReportingCountry][LaboratoryCode] [Patient Counter][Pathogen] [Specimen][Antibiotic][DateUsedForStatistics]” Yes (Error) String (Max length: 80) VariableName Description Required (what happens if not submitted) Data type Code 2 - RecordType Structure and format of the data Yes (Error) Coded Value AMRTEST (fixed value for EARS-Net/CAESAR) VariableName Description Required Data type Code 3 – RecordTypeVersion There may be more than one version of a RecordType. This element indicates which version the sender uses when generating the message Yes Numeric 2 (CAESAR uses AMRTEST version 2) VariableName Description Required (what happens if not submitted) Data type Code 4 - Subject Subject of the data to report Yes (Error) Coded Value AMR (fixed value for EARS-Net/CAESAR) VariableName Description Required (what happens if not submitted) Data type Code 5 - DataSource The data source (surveillance system) that the record originates from Yes (Error) Coded Value <Name of the national surveillance> to be decided, and then fixed VariableName Description Required (what happens if not submitted) Data type Code 6 - ReportingCountry The country reporting the record Yes (Error) Coded Value Two letter country codes, same as Internet suffix VariableName Description Required (what happens if not submitted) Data type Code 7 – DateUsedForStatistics Date when sample was taken Yes (Error) Date Exact date only, “YYYY-MM-DD” 30 Technical variables VariableName Description Required Data type Code 8 - Status Status of reporting “NEW/UPDATE” or “DELETE” Default if left out: NEW/UPDATE. If set to DELETE, the record with the given RecordId will be deleted from the database (or better stated, invalidated). If set to NEW/UPDATE or left empty, the record is entered into the database. If the same recorded was already present, that record will be replaced. Yes Coded Value NEW/UPDATE OR DELETE Epidemiological variables at isolate level VariableName Description Required (what happens if not submitted) Data type 9 - LaboratoryCode Laboratory code unique for each laboratory within the country Yes Error Coded Value Recommended format: [ReportingCountry]-[code of three characters] VariableName Description Required Data type Code 10 - Specimen The source of the isolate (e.g. blood) Yes (Ignore): data entry is required; however, if you enter data that does not meet the requested combination of “Pathogen”, “Specimen” and “Antibiotic”, the record is ignored. Coded Value BLOOD = blood; CSF = cerebrospinal fluid VariableName Description Required (what happens if not submitted) Data type Code 11 - PatientCounter Numeric code for each patient, unique within laboratory; anonymous code by laboratory to specify patient Yes (Error) Numeric (integer) Required that laboratories anonymize the PatientCounter VariableName Description Required (what happens if not submitted) Data type Code 12 - Gender Gender Yes (Warning) Coded Value M = Male; F = Female; O = Other; UNK = Unknown VariableName Description Required (what happens if not submitted) Data type Code 13 - Age Age of the patient when the sample was taken Yes (Warning) Numeric Integer VariableName Description Required Data type 14 - IsolateId Isolate ID; code for each isolate, unique within laboratory and year Text code assigned by laboratory to specify isolate Yes (Warning) Text 31 Epidemiological variables at isolate level VariableName Description Required (what happens if not submitted) Data type Code 15 - HospitalId Unique identifier for the hospital within each laboratory Yes (Warning) Text Unique identifier for the hospital within each laboratory; recommended format: [LaboratoryCode]-[letter assigned to a hospital – starting from A, B, C, etc.] VariableName Description Required (what happens if not submitted) Data type Code 16 - PatientType Origin of patient: is the patient at the moment the isolate is taken admitted in a hospital (inpatient) or not. Patients who go to the hospital for dialysis, other day hospital care and to the emergency room should be classified as “O” for the field “PatientType”. All other patients who are admitted in the hospital as inpatients should be classified as “INPAT”. Yes (Warning) Coded Value INPAT= Admitted (Inpatient); OUTPAT= Outpatient; O =Other (e.g. emergency room); UNK=Unknown VariableName Description Required (what happens if not submitted) Data type Code 17 - HospitalUnitType Hospital department (at sample collection) Yes (Warning) Coded Value INTMED =Internal Medicine; PEDS =Paediatrics/neonatal; PEDSICU=Paediatrics/neonatal ICU; SURG =Surgery; ONCOL=Haematology/ Oncology; OBGYN=Obstetrics/Gynaecology; ICU=Intensive Care Unit; ED=Emergency Department; URO=Urology Ward; INFECT=Infectious Disease Ward; O =Other; UNK=Unknown VariableName Description Required (what happens if not submitted) Data type Code 18 - Pathogen Pathogen species and genus of the pathogen that has been isolated from the sample Yes (Error) Coded Value STRPNE=Streptococcus pneumoniae STAAUR=Staphylococcus aureus ENCFAE=Enterococcus faecalis ENCFAI=Enterococcus faecium ESCCOL=Escherichia coli KLEPNE=Klebsiella pneumoniae PSEAER=Pseudomonas aeruginosa ACISPP= Acinetobacter species VariableName Description Required Data type Code 19 - DateOfHospitalisation Date of admission in hospital No Date Exact date only, “YYYY-MM-DD” VariableName Description Required Data type Code Validation rule 20 - ResultPCRmec Detection of PCR mecA-gene No Coded Value POS=positive; NEG=negative; UNK=unknown To be reported only if Pathogen=STAAUR VariableName Description Required Data type Code Validation rule 21 - ResultPbp2aAggl Detection of PBP2a-agglutination No Coded Value POS=positive; NEG=negative; UNK=unknown To be reported only if Pathogen=STAAUR C H A PT ER 8 32 Epidemiological variables at isolate level VariableName Description Required Data type Code Validation rule 22 - Serotype Serotype/group of the pathogen isolated from the sample. Reference: Danish Kauffman-Lund scheme from the WHO Collaborating Centre for Reference and Research on Pneumococci at the Danish Serum Institute. No Coded Value See Annex 6 To be reported only if Pathogen=STRPNE VariableName Description Required Data type Code Validation rule 23 - ESBL Detection of ESBL No Coded Value POS=positive; NEG=negative; UNK=unknown To be reported only if Pathogen= ESCCOL or KLEPNE VariableName Description Required Data type Code Validation rule 24 - ResultCarbapenemases Detection of carbapenemases; this refers to phenotypic test for carbapenemase activity (e.g. the modified Hodge test - MHT). No Coded Value POS=positive; NEG=negative; UNK=unknown To be reported only if Pathogen= ESCCOL or KLEPNE or PSEAER. Epidemiological variables at AMR test level VariableName Description Required Data type Code 25 - Antibiotic Antibiotic code Yes (Ignore): data entry is required; however, if you enter data that does not meet the requested combination of “Pathogen”, “Specimen” and “Antibiotic”, the record is ignored. By ignored, we mean that data on these combinations will not be reported Coded Value See Annex 4 VariableName Description Required (what happens if not submitted) Data Type Code 26 - SIR Final interpretation result of all different susceptibility tests performed Yes (Error) Coded Value S=susceptible; I=intermediate; R=resistant VariableName Description Required Data type Code 27 - ResultZoneSign Zone (> < =); this field can indicate if a value of the zone diameter of the disk test is «less than» (<); “equal to or less than” (< =); «equal to» (=); “equal to or greater than” (>=); or «greater than» (>) the value indicated in the following field. No Coded Value <; <; =; = >; = > VariableName Description Required Data type Code 28 - ResultZoneValue Zone (Value in mm) No Numeric Integer VariableName Description Required Data type Code 29 - ResultZoneSIR Interpretation of the zone test No Coded Value S=susceptible; I=intermediate; R=resistant 33 Epidemiological variables at AMR test level VariableName Description Required Data type Code 30 - ResultMICSign MIC (> < =); this field can indicate if a value of the zone diameter of the MIC test is «less than» (<); “equal to or less than” (< =); «equal to» (=); “equal to or greater than” (>=); or «greater than» (>) the value indicated in the following field. No Coded Value <; <; =; = >; = > VariableName Description Required Data Type 31 - ResultMICValue MIC (Value in mg/l) No Numeric VariableName Description Required Data type Code 32 - ResultMICSIR Interpretation of the MIC test. No Coded Value S=susceptible; I=intermediate; R=resistant VariableName Description Required Data type Code 33 - ResultEtestSign Gradient strip test (> < =); this field can indicate if a value of the zone diameter of the gradient strip test is “less than” (<); “equal to or less than” (< =); “equal to” (=); “equal to or greater than” (>=); or “greater than” (>) the value indicated in the following field. No Coded Value <; <; =; = >; = > VariableName Description Required Data type Code 34 - ResultEtestValue Gradient strip test MIC (Value in mg/l) No Numeric If <1 then float, if >=1 then integer; the value 1.5 is also allowed VariableName Description Required Data Type Code 35 – ResultEtestSIR Interpretation of the gradient strip test No Coded Value S=susceptible; I=intermediate; R=resistant VariableName Description Required Data type Code 36 - DiskLoad Disk content (only if Zone); this field can be used to mention the load of the antibiotic disk used. Please mention the value and the Units (e.g. mcg, Units or IU). No Text Value and units: i.e. UI, mcg VariableName Description Required Data type Code 37 - ReferenceGuidelinesSIR To differentiate use of CLSI and EUCAST guidelines for breakpoints No Coded Value EUCAST = European Committee on Antimicrobial Susceptibility Testing CLSI = Clinical and Laboratory Standards Institute NAT = National O = Other C H A PT ER 8 CHAPTER 9 35 Denominator questionnaire CAESAR laboratory and hospital questionnaire When analysing AMR surveillance data, it is important to have background information of the laboratories and hospitals. This information provides a better understanding of the patient population from which the resistance data are collected and enables calculation of incidence. When a country starts to participate in CAESAR, the AMR focal point is asked to distribute a small questionnaire to the participating laboratories and hospitals. Every year a request will be sent out to update the information provided. Which questions and why? The AMR focal point is asked to provide an estimate of the catchment population/population coverage of the laboratories participating in the national AMR network providing data to CAESAR. Laboratories are asked to provide the following information. 1. The town and postal code in order to determine the geographic distribution of the laboratories participating in the network. 2. The CAESAR hospital codes for the hospitals served by the laboratory. This information enables the anonymous determination of the proportion of resistance per hospital and the diversity of resistance between hospitals in a country (especially for the mainly hospital-acquired infections, such as MRSA or P. aeruginosa). 3. If available, provide the total number of blood culture sets used in the past year. One request/set consists of any number of blood culture bottles that are taken from one patient on a single occasion for diagnostic purposes. The total number of blood culture sets in relation to the total number of hospital beds or patient days (of all hospitals the laboratory serves) gives an indication of the blood culturing habits. For example, if the number of blood culture sets taken per hospital beds/patient days is very low, this could mean that blood cultures are only taken in cases of therapeutic failure. The chance of an isolate being resistant increases with therapeutic failure. Therefore, the proportion of resistance would be overestimated if blood cultures are only taken in cases of therapeutic failure. Hospitals are asked to provide: 1. level of care to determine the patient mix; 2. number of hospital beds; 3. number of hospital intensive care beds; 4. number of hospital patient days, or if not available the annual occupancy rate of beds; and 5. number of hospital admissions. C H A PT ER 9 36 Laboratory questionnaire 20.. (please complete the questionnaire for each laboratory participating in CAESAR) 1. CAESAR laboratory code: (e.g. BR001) 2. Postal code of the laboratory: 3. City: 4. The total number of blood culture requests (sets)11 12 in 20..: 5. Please provide the CAESAR hospital codes for all hospitals served by your laboratory and, if available, specify the total number of blood culture requests (sets) in 20.. per hospital served: 11 One request/set consists of any number of blood culture bottles that are taken from one patient on a single occasion for diagnostic purposes. 12 If not available, please calculate by dividing the total number of blood culture bottles processed, by the total number of bottles per blood culture request (set). No. CAESAR hospital code Hospital-specific number of blood culture requests (sets) 1 (for example BR001A) 2 (for example BR001B) 3 (for example BR001C) 4 5 6 7 37 1. CAESAR hospital code: (for example BR001A) 2. CAESAR laboratory code: (for example BR001) 3. Postal code of the hospital: 4. City of the hospital: 5. The level of care of the hospital : □ Primary level13 (Important: check definitions) □ Secondary level14 □ Tertiary level15 □ Different, please specify: 6. Best estimate of catchment population of your hospital in 20..16: (contact hospital administration) 7. Hospital size in beds in 20..: (number of beds) 8. Number of intensive care beds in 20..: (number of beds) 9. Total number of patient days17 in 20..: (number of patient days) OR (if not available at all) 10. The average occupancy rate in 20..: (%) 11. Total number of patient admissions in 20..: (number of admissions) Hospital questionnaire 20.. (please complete the questionnaire for each hospital participating in CAESAR) 13 Primary level, often referred to as a district hospital or first-level referral. The hospital has few specialities, mainly internal medicine, obstetrics-gynaecology, paediatrics, and general surgery, or only general practice; limited laboratory services are available for general, but not for specialized pathological analysis; bed capacity ranges from 30 to 200 beds. 17 Patient days: the number of patient days is the number of days spent in the institution for all patients occupying a bed. A day is measured at midnight, and the day of discharge is not counted as an extra day. This means that a patient admitted today and discharged tomorrow will have one patient day. Day patients will have zero patient days as they do not stay past midnight and must not be included in the total count. 16 We realise that university/teaching hospitals may also serve as district hospitals, thereby actually serving two different populations. If this is the case for your hospital, please provide the catchment population for the university/tertiary care service. 15 Tertiary level often referred to as central, regional or tertiary-level hospital. Highly specialized staff and technical equipment, e.g. cardiology, ICU and specialized imaging units; clinical services are highly differentiated by function; may have teaching activities; bed capacity ranges from 300 to 1,500 beds. 14 Secondary level often referred to as a provincial hospital. Highly differentiated by function with five to ten clinical specialities; bed capacity ranging from 200 to 800 beds. C H A PT ER 9 38 ANNEX 1 39 Letter of Agreement Letter of Agreement Between the WHO Regional Office for Europe, on behalf of the Central Asian and Eastern European Surveillance on Antibiotic Resistance (CAESAR) network (WHO/Europe and/or the CAESAR network, as the case may be) and ……………………………, on behalf of …………………., being the national AMR focal point in [Country] The CAESAR network is an initiative of the WHO/Europe undertaken in collaboration with the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the National Institute of Public Health and the Environment (RIVM) in the Netherlands. The CAESAR network collaborates closely with the European Centre for Disease Control (ECDC). The CAESAR network aims to collect and aggregate comparable and reliable antibiotic resistance data for public health purposes. NAMRSS wishes to cooperate with the CAESAR network, through the sharing of quantitative resistance data on: □ Streptococcus pneumoniae □ Staphylococcus aureus □ Klebsiella pneumoniae □ Escherichia coli □ Enterococcus faecium/faecalis □ Pseudomonas aeruginosa □ Acinetobacter spp. WHO/Europe Member States are encouraged to collect and share the data of the pathogens mentioned above, as they represent clinically and epidemiologically relevant antibiotic resistance traits. In addition, national surveillance on other relevant pathogens is encouraged. The parties agree as follows: 1. ………… shall ensure that the participating laboratories in [Country] make individual data available to ……….. and those laboratories participate in the intended quality assessment exercises. 2. …………. will collect the individual data from the participating laboratories and forward such data to the CAESAR network through WHO/Europe. 3. …………. shall ensure that it has the full legal right to share the data with the CAESAR network through WHO/Europe for the purpose of this Letter of Agreement and that such data does not violate any intellectual property rights of any third party. 4. WHO/Europe will accept no liability or responsibility on the grounds that the data is a violation of the above warranty. WHO/Europe will transfer any claims to ………… made by third parties concerning A N N EX 1 40 the use of the data by WHO/Europe and the CAESAR network and ………… will deal directly with such thirdparty claims. 5. The transfer of the data to WHO shall not convey any intellectual property rights in the data to WHO/ Europe. 6. ……………. will share collated data on antibiotic resistance collected through the CAESAR network with the participating laboratories in [Country]. …………. shall keep the participating laboratories informed on the progress of the CAESAR network. 7. WHO/Europe shall make the collected data available through the Internet on a dedicated platform. Data will be anonymized to a level where individual laboratories or hospitals are not identifiable. WHO/Europe shall keep the ………… informed on the progress of the CAESAR network, related activities and annual reports. 8. Both parties intend to provide comparable and correct data, but none of the parties hereto warrants that the data it provides hereunder are complete and correct; nor shall have any liability to the other for any errors or omissions in such data, or the results from the use thereof. 9. Participating national institutions to the CAESAR network will be acknowledged as the source in any publication derived from their data contribution. In peer-reviewed papers, ……….. will, depending on the journal, either be included as author, be part of the working group or mentioned in the acknowledgement. 10. The use of one Party’s emblem or name by the other Party is subject to prior approval in writing. 11. The Parties will resolve any difference of interpretation or application of this Letter of Agreement by the appointment of representatives from each Party through consultations or negotiations. 12. Nothing contained herein shall be construed as a waiver of any of the privileges and immunities enjoyed by WHO/Europe under national or international law and/or as submitting WHO/Europe to any national court or jurisdiction. Institution: Institution: WHO Office for Europe o Division of Communicable Disease Health Security , and Environment City: City: DK-2100 Copenhagen Country: Country: Denmark Name: Name: Dr Danilo Lo Fo Wong Date: Date: Signature: Signature: 41 A N N EX 1 42 ANNEX 2 43 Isolate record forms Kindly provided by EARS-Net, ECDC Isolate record forms are now available as Microsoft-Excel-based data entry forms, enabling the electronic capture of CAESAR data at local laboratory level without the need for a dedicated laboratory information system. Data are stored in .xls spreadsheet format and are readily exported in the required CAESAR data format. Additionally, the data entry form automatically checks for completeness, and it ensures sensible data. The data form can be configured to show only the pathogens and antibiotics tested in the laboratory, and can be translated into any language. The required configuration and translation can be made by any user, without the need for programming skills. The data entry form and instructions for configuration, translation and use can be obtained from the international data manager by email (caesar@rivm.nl). A N N EX 2 44 Laboratory Code “LaboratoryCode” Isolate sample number “IsolateId” max. 12 characters Isolate source “Specimen” □ Blood □ CSF Date of sample collection “DateUsedForStatistics” (yyyy-mm-dd ) Patient ID / Code max. 12 characters Gender □ Man □ Female □ Other □ Unknown Year of birth (yyyy) Code of hospital “HospitalId” Origin of patient “PatientType” □ Inpatient □ Outpatient □ Other □ Unknown Date of admission “DateOfHospitalisation” (yyyy-mm-dd) Hospital Department “HospitalUnitType” □ Internal medicine □ Paediatrics/neonatal □ Paediatrics/neonatal ICU □ Surgery □ Haematology/Oncology □ Obstetrics/Gynaecology □ Intensive care unit □ Emergency department □ Urology department □ Infectious disease ward □ Other □ Unknown Antibiotic SIR (final interpretation result of all different susceptibility test performed) Fill in S, I or R Zone diameter (ResultZoneValue) (mm) Zone diameter interpretation (ResultZoneSIR) Fill in S, I or R MIC (ResultMICValue) (mg/l) MIC interpretation (ResultMICSIR) Fill in S, I or R E-test (ResultEtestValue) (mg/l) E-test interpretation (ResultEtestSIR) Fill in S, I or R Oxacillin Disk load: □ □ □ □ - - - - - - □ - - - - - - □ Penicillin □ □ □ □ - - - - - - □ - - - - - - □ Erythromycin Clarithromycin Azithromycin □ □ □ □ □ □ □ □ □ □ □ □ - - - - - - - - - - - - - - - - - - □ □ □ - - - - - - - - - - - - - - - - - - □ □ □ Cefotaxime Ceftriaxone □ □ □ □ □ □ □ □ - - - - - - - - - - - - □ □ - - - - - - - - - - - - □ □ Norfloxacin Levofloxacin Moxifloxacin □ □ □ □ □ □ □ □ □ □ □ □ - - - - - - - - - - - - - - - - - - □ □ □ - - - - - - - - - - - - - - - - - - □ □ □ Serotype: Isolate Record Form S. pneumoniae Instructions: Please send data of the first blood and/or cerebrospinal fluid (CSF) - isolate of every patient with an invasive S. aureus infection. Send data on resistant and susceptible isolates; use 1 form per isolate Antibiotic susceptibility testing (S/I/R, zone and/or MIC) Send this form to (Name/Institute/Contact details): 45 A N N EX 2 Laboratory Code “LaboratoryCode” Isolate sample number “IsolateId” max. 12 characters Isolate source “Specimen” □ Blood Date of sample collection “DateUsedForStatistics” (yyyy-mm-dd ) Patient ID / Code max. 12 characters Gender □ Man □ Female □ Other □ Unknown Year of birth (yyyy) Code of hospital “HospitalId” Origin of patient “PatientType” □ Inpatient □ Outpatient □ Other □ Unknown Date of admission “DateOfHospitalisation” (yyyy-mm-dd) Hospital Department “HospitalUnitType” □ Internal medicine □ Paediatrics/neonatal □ Paediatrics/neonatal ICU □ Surgery □ Haematology/Oncology □ Obstetrics/Gynaecology □ Intensive care unit □ Emergency department □ Urology department □ Infectious disease ward □ Other □ Unknown Antibiotic SIR (final interpretation result of all different susceptibility test performed) Fill in S, I or R Zone diameter (ResultZoneValue) (mm) Zone diameter interpretation (ResultZoneSIR) Fill in S, I or R MIC (ResultMICValue) (mg/l) MIC interpretation (ResultMICSIR) Fill in S, I or R E-test (ResultEtestValue) (mg/l) E-test interpretation (ResultEtestSIR) Fill in S, I or R Cefoxitin Disk load: □ □ □ □ - - - - - - □ - - - - - - □ Oxacillin Methicillin Flucloxacillin Cloxacillin Dicloxacillin □ □ □ □ □ □ □ □ □ □ □ □ □ □ □ □ - - - - - - - - - - - - - - - - - - - - - - - - □ □ □ □ - - - - - - - - - - - - - - - - - - - - - - - - □ □ □ □ Ciprofloxacin Ofloxacin Levofloxacin Norfloxacin □ □ □ □ □ □ □ □ □ □ □ □ □ □ □ □ - - - - - - - - - - - - - - - - - - - - - - - - □ □ □ □ - - - - - - - - - - - - - - - - - - - - - - - - □ □ □ □ Rifampicin □ □ □ □ - - - - - - □ - - - - - - □ Linezolid □ □ □ □ - - - - - - □ - - - - - - □ Vancomycin □ □ □ □ - - - - - - □ - - - - - - □ Daptomycin □ □ □ □ - - - - - - □ - - - - - - □ Isolate Record Form S. aureus To be filled out by laboratory Instructions: Please send data of the first blood - isolate of every patient with an invasive S. aureus infection. Send data on resistant and susceptible isolates; use 1 form per isolatee Antibiotic susceptibility testing (S/I/R, zone and/or MIC) Send this form to (Name/Institute/Contact details): 46 Laboratory Code “LaboratoryCode” Isolate sample number “IsolateId” max. 12 characters Isolate source “Specimen” □ Blood Date of sample collection “DateUsedForStatistics” (yyyy-mm-dd ) Patient ID / Code max. 12 characters Gender □ Man □ Female □ Other □ Unknown Year of birth (yyyy) Code of hospital “HospitalId” Origin of patient “PatientType” □ Inpatient □ Outpatient □ Other □ Unknown Date of admission “DateOfHospitalisation” (yyyy-mm-dd) Hospital Department “HospitalUnitType” □ Internal medicine □ Paediatrics/neonatal □ Paediatrics/neonatal ICU □ Surgery □ Haematology/Oncology □ Obstetrics/Gynaecology □ Intensive care unit □ Emergency department □ Urology department □ Infectious disease ward □ Other □ Unknown Antibiotic SIR (final interpretation result of all different susceptibility test performed) Fill in S, I or R Zone diameter (ResultZoneValue) (mm) Zone diameter interpretation (ResultZoneSIR) Fill in S, I or R MIC (ResultMICValue) (mg/l) MIC interpretation (ResultMICSIR) Fill in S, I or R E-test (ResultEtestValue) (mg/l) E-test interpretation (ResultEtestSIR) Fill in S, I or R Amoxicillin Ampicillin □ □ □ □ □ □ □ □ - - - - - - - - - - - - □ □ - - - - - - - - - - - - □ □ Gentamicin High Disk load □ □ □ □ - - - - - - □ - - - - - - □ Vancomycin □ □ □ □ - - - - - - □ - - - - - - □ Teicoplanin □ □ □ □ - - - - - - □ - - - - - - □ Linezolid □ □ □ □ - - - - - - □ - - - - - - □ Isolate Record Form □ E. faecium □ E. faecalis To be filled out by laboratory Instructions: Please send data of the first blood - isolate of every patient with an invasive E. faecium and E. faecalis infection (please specify by ticking relevant box above). Send data on resistant and susceptible isolates; use 1 form per isolate Antibiotic susceptibility testing (S/I/R, zone and/or MIC) Send this form to (Name/Institute/Contact details): 47 Laboratory Code “LaboratoryCode” Isolate sample number “IsolateId” max. 12 characters Isolate source “Specimen” □ Blood □ CSF Date of sample collection “DateUsedForStatistics” (yyyy-mm-dd ) Patient ID / Code max. 12 characters Gender □ Man □ Female □ Other □ Unknown Year of birth (yyyy) Code of hospital “HospitalId” Origin of patient “PatientType” □ Inpatient □ Outpatient □ Other □ Unknown Date of admission “DateOfHospitalisation” (yyyy-mm-dd) Hospital Department “HospitalUnitType” □ Internal medicine □ Paediatrics/neonatal □ Paediatrics/neonatal ICU □ Surgery □ Haematology/Oncology □ Obstetrics/Gynaecology □ Intensive care unit □ Emergency department □ Urology department □ Infectious disease ward □ Other □ Unknown Antibiotic SIR (final interpretation result of all different susceptibility test performed) Fill in S, I or R Zone diameter (ResultZoneValue) (mm) Zone diameter interpretation (ResultZoneSIR) Fill in S, I or R MIC (ResultMICValue) (mg/l) MIC interpretation (ResultMICSIR) Fill in S, I or R E-test (ResultEtestValue) (mg/l) E-test interpretation (ResultEtestSIR) Fill in S, I or R Amoxicillin Ampicillin □ □ □ □ □ □ □ □ - - - - - - - - - - - - □ □ - - - - - - - - - - - - □ □ Amoxicillin clavulanic acid Piperacillin- Tazobactam □ □ □ □ □ □ □ □ - - - - - - - - - - - - □ □ - - - - - - - - - - - - □ □ Gentamicin Tobramycin Amikacin Netilimicin □ □ □ □ □ □ □ □ □ □ □ □ □ □ □ □ - - - - - - - - - - - - - - - - - - - - - - - - □ □ □ □ - - - - - - - - - - - - - - - - - - - - - - - - □ □ □ □ Ciprofloxacin Ofloxacin Levofloxacin Moxifloxacin □ □ □ □ □ □ □ □ □ □ □ □ □ □ □ □ - - - - - - - - - - - - - - - - - - - - - - - - □ □ □ □ - - - - - - - - - - - - - - - - - - - - - - - - □ □ □ □ Cefotaxime Ceftriaxone Ceftazidime □ □ □ □ □ □ □ □ □ □ □ □ - - - - - - - - - - - - - - - - - - □ □ □ - - - - - - - - - - - - - - - - - - □ □ □ Cefipime □ □ □ □ - - - - - - □ - - - - - - □ Imipenem Meropenem Doripenem Ertapenem □ □ □ □ □ □ □ □ □ □ □ □ □ □ □ □ - - - - - - - - - - - - - - - - - - - - - - - - □ □ □ □ - - - - - - - - - - - - - - - - - - - - - - - - □ □ □ □ Colistin Polymixin B □ □ □ □ □ □ □ □ - - - - - - - - - - - - □ □ - - - - - - - - - - - - □ □ Tigecycline □ □ □ □ - - - - - - □ - - - - - - □ Isolate Record Form E. coli To be filled out by laboratory Instructions: Please send data of the first blood and/or cerebrospinal fluid (CSF) - isolate of every patient with an invasive E. coli infection. Send data on resistant and susceptible isolates; use 1 form per isolate Antibiotic susceptibility testing (S/I/R, zone and/or MIC) Send this form to (Name/Institute/Contact details): A N N EX 2 48 Laboratory Code “LaboratoryCode” Isolate sample number “IsolateId” max. 12 characters Isolate source “Specimen” □ Blood □ CSF Date of sample collection “DateUsedForStatistics” (yyyy-mm-dd ) Patient ID / Code max. 12 characters Gender □ Man □ Female □ Other □ Unknown Year of birth (yyyy) Code of hospital “HospitalId” Origin of patient “PatientType” □ Inpatient □ Outpatient □ Other □ Unknown Date of admission “DateOfHospitalisation” (yyyy-mm-dd) Hospital Department “HospitalUnitType” □ Internal medicine □ Paediatrics/neonatal □ Paediatrics/neonatal ICU □ Surgery □ Haematology/Oncology □ Obstetrics/Gynaecology □ Intensive care unit □ Emergency department □ Urology department □ Infectious disease ward □ Other □ Unknown Antibiotic SIR (final interpretation result of all different susceptibility test performed) Fill in S, I or R Zone diameter (ResultZoneValue) (mm) Zone diameter interpretation (ResultZoneSIR) Fill in S, I or R MIC (ResultMICValue) (mg/l) MIC interpretation (ResultMICSIR) Fill in S, I or R E-test (ResultEtestValue) (mg/l) E-test interpretation (ResultEtestSIR) Fill in S, I or R Amoxicillin clavulanic acid Piperacillin- Tazobactam □ □ □ □ □ □ □ □ - - - - - - - - - - - - □ □ - - - - - - - - - - - - □ □ Gentamicin Tobramycin Amikacin Netilimicin □ □ □ □ □ □ □ □ □ □ □ □ □ □ □ □ - - - - - - - - - - - - - - - - - - - - - - - - □ □ □ □ - - - - - - - - - - - - - - - - - - - - - - - - □ □ □ □ Ciprofloxacin Ofloxacin Levofloxacin Moxifloxacin Nalidixic acid □ □ □ □ □ □ □ □ □ □ □ □ □ □ □ □ □ □ □ □ - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - □ □ □ □ □ - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - □ □ □ □ □ Cefotaxime Ceftriaxone Ceftazidime □ □ □ □ □ □ □ □ □ □ □ □ - - - - - - - - - - - - - - - - - - □ □ □ - - - - - - - - - - - - - - - - - - □ □ □ Cefipime □ □ □ □ - - - - - - □ - - - - - - □ Imipenem Meropenem Doripenem Ertapenem □ □ □ □ □ □ □ □ □ □ □ □ □ □ □ □ - - - - - - - - - - - - - - - - - - - - - - - - □ □ □ □ - - - - - - - - - - - - - - - - - - - - - - - - □ □ □ □ Colistin Polymixin B □ □ □ □ □ □ □ □ - - - - - - - - - - - - □ □ - - - - - - - - - - - - □ □ Tigecycline □ □ □ □ - - - - - - □ - - - - - - □ Isolate Record Form K. pneumoniae To be filled out by laboratory Instructions: Please send data of the first blood and/or cerebrospinal fluid (CSF) - isolate of every patient with an invasive K. pneumoniae infection. Send data on resistant and susceptible isolates; use 1 form per isolate Antibiotic susceptibility testing (S/I/R, zone and/or MIC) Send this form to (Name/Institute/Contact details): 49 A N N EX 2 Laboratory Code “LaboratoryCode” Isolate sample number “IsolateId” max. 12 characters Isolate source “Specimen” □ Blood □ CSF Date of sample collection “DateUsedForStatistics” (yyyy-mm-dd ) Patient ID / Code max. 12 characters Gender □ Man □ Female □ Other □ Unknown Year of birth (yyyy) Code of hospital “HospitalId” Origin of patient “PatientType” □ Inpatient □ Outpatient □ Other □ Unknown Date of admission “DateOfHospitalisation” (yyyy-mm-dd) Hospital Department “HospitalUnitType” □ Internal medicine □ Paediatrics/neonatal □ Paediatrics/neonatal ICU □ Surgery □ Haematology/Oncology □ Obstetrics/Gynaecology □ Intensive care unit □ Emergency department □ Urology department □ Infectious disease ward □ Other □ Unknown Antibiotic SIR (final interpretation result of all different susceptibility test performed) Fill in S, I or R Zone diameter (ResultZoneValue) (mm) Zone diameter interpretation (ResultZoneSIR) Fill in S, I or R MIC (ResultMICValue) (mg/l) MIC interpretation (ResultMICSIR) Fill in S, I or R E-test (ResultEtestValue) (mg/l) E-test interpretation (ResultEtestSIR) Fill in S, I or R Piperacillin Piperacillin- tazobactam □ □ □ □ □ □ □ □ - - - - - - - - - - - - □ □ - - - - - - - - - - - - □ □ Gentamicin Tobramycin Amikacin Netilimicin □ □ □ □ □ □ □ □ □ □ □ □ □ □ □ □ - - - - - - - - - - - - - - - - - - - - - - - - □ □ □ □ - - - - - - - - - - - - - - - - - - - - - - - - □ □ □ □ Ciprofloxacin Levofloxacin □ □ □ □ □ □ □ □ - - - - - - - - - - - - □ □ - - - - - - - - - - - - □ □ Ceftazidime Cefipime □ □ □ □ □ □ □ □ - - - - - - - - - - - - □ □ - - - - - - - - - - - - □ □ Imipenem Meropenem Doripenem □ □ □ □ □ □ □ □ □ □ □ □ - - - - - - - - - - - - - - - - - - □ □ □ - - - - - - - - - - - - - - - - - - □ □ □ Colistin Polymixin B □ □ □ □ □ □ □ □ - - - - - - - - - - - - □ □ - - - - - - - - - - - - □ □ Isolate Record Form P. aeruginosa To be filled out by laboratory Instructions: Please send data of the first blood and/or cerebrospinal fluid (CSF) - isolate of every patient with an invasive P. aeruginosa infection. Send data on resistant and susceptible isolates; use 1 form per isolate Antibiotic susceptibility testing (S/I/R, zone and/or MIC) Send this form to (Name/Institute/Contact details): 50 Laboratory Code “LaboratoryCode” Isolate sample number “IsolateId” max. 12 characters Isolate source “Specimen” □ Blood □ CSF Date of sample collection “DateUsedForStatistics” (yyyy-mm-dd ) Patient ID / Code max. 12 characters Gender □ Man □ Female □ Other □ Unknown Year of birth (yyyy) Code of hospital “HospitalId” Origin of patient “PatientType” □ Inpatient □ Outpatient □ Other □ Unknown Date of admission “DateOfHospitalisation” (yyyy-mm-dd) Hospital Department “HospitalUnitType” □ Internal medicine □ Paediatrics/neonatal □ Paediatrics/neonatal ICU □ Surgery □ Haematology/Oncology □ Obstetrics/Gynaecology □ Intensive care unit □ Emergency department □ Urology department □ Infectious disease ward □ Other □ Unknown Antibiotic SIR (final interpretation result of all different susceptibility test performed) Fill in S, I or R Zone diameter (ResultZoneValue) (mm) Zone diameter interpretation (ResultZoneSIR) Fill in S, I or R MIC (ResultMICValue) (mg/l) MIC interpretation (ResultMICSIR) Fill in S, I or R E-test (ResultEtestValue) (mg/l) E-test interpretation (ResultEtestSIR) Fill in S, I or R Ciprofloxacin Levofloxacin □ □ □ □ □ □ □ □ - - - - - - - - - - - - □ □ - - - - - - - - - - - - □ □ Gentamicin Tobramycin Amikacin Netilimicin □ □ □ □ □ □ □ □ □ □ □ □ □ □ □ □ - - - - - - - - - - - - - - - - - - - - - - - - □ □ □ □ - - - - - - - - - - - - - - - - - - - - - - - - □ □ □ □ Imipenem Meropenem Doripenem □ □ □ □ □ □ □ □ □ □ □ □ - - - - - - - - - - - - - - - - - - □ □ □ - - - - - - - - - - - - - - - - - - □ □ □ Colistin Polymixin B □ □ □ □ □ □ □ □ - - - - - - - - - - - - □ □ - - - - - - - - - - - - □ □ Isolate Record Form Acinetobacter spp To be filled out by laboratory Instructions: Please send data of the first blood and/or cerebrospinal fluid (CSF) - isolate of every patient with an invasive Acinetobacter spp infection. Send data on resistant and susceptible isolates; use 1 form per isolate Antibiotic susceptibility testing (S/I/R, zone and/or MIC) Send this form to (Name/Institute/Contact details): 51 A N N EX 2 52 ANNEX 3 53 List of EARS-Net/CAESAR pathogens A N N EX 3 Code Name ENCFAE Enterococcus faecalis ENCFAI Enterococcus faecium ESCCOL Escherichia coli KLEPNE Klebsiella pneumoniae PSEAER Pseudomonas aeruginosa STAAUR Staphylococcus aureus STRPNE Streptococcus pneumoniae ACISPP Acinetobacter spp. 54 ANNEX 4 55 List of S. pneumoniae serotypes (Kauffman-Lund scheme) Code Description 1 Type 1 2 Type 2 3 Type 3 4 Type 4 5 Type 5 6 Group 6 6A Type 6A 6B Type 6B 6C Type 6C 6D Type 6D 7 Group 7 7A Type 7A B Type 7B 7C Type 7C 7F Type 7F 8 Type 8 9 Group 9 9A Type 9A 9L Type 9L 9N Type 9N 9V Type 9V 10 Group 10 10A Type 10A 10B Type 10B 10C Type 10C 10F Type 10F 11 Group 11 11A Type 11A 11B Type 11B 11C Type 11C 11D Type 11D 11F Type 11F 12 Type 12 12A Type 12A 12B Type 12B 12F Type 12F 13 Type 13 14 Type 14 15 Group 15 Code Description 15A Type 15A 15B Type 15B 15C Type 15C 15F Type 15F 16 Group 16 16A Type 16A 16F Type 16F 17 Group 17 17A Type 17A 17F Type 17F 18 Group 18 18A Type 18A 18B Type 18B 18C Type 18C 18F Type 18F 19 Group 19 19A Type 19A 19B Type 19B 19C Type 19C 19F Type 19F 20 Type 20 21 Type 21 22 Group 22 22A Type 22A 22F Type 22F 23 Group 23 23A Type 23A 23B Type 23B 23F Type 23F 24 Group 24 24A Type 24A 24B Type 24B 24F Type 24F 25 Group 25 25A Type 25A 25F Type 25F 27 Type 27 28 Group 28 28A Type 28A Code Description 28F Type 28F 29 Type 29 31 Type 31 32 Group 32 32A Type 32A 32F Type 32F 33 Group 33 33A Type 33A 33B Type 33B 33C Type 33C 33D Type 33D 33F Type 33F 34 Type 34 35 Group 35 35A Type 35A 35B Type 35B 35C Type 35C 35F Type 35F 36 Type 36 37 Type 37 38 Type 38 39 Type 39 40 Type 40 41 Group 41 41A Type 41A 41F Type 41F 42 Type 42 43 Type 43 44 Type 44 45 Type 45 46 Type 46 47 Group 47 47A Type 47A 47F Type 47F 48 Type 48 UNK Unknown NA Not applicable A N N EX 4 World Health Organization Regional Office for Europe UN City, Marmorvej 51 DK-2100 Copenhagen Ø, Denmark Tel.: +45 45 33 70 00 Fax: +45 45 33 70 01 Email: contact@euro.who.int Website: www.euro.who.int The WHO Regional Office for Europe The World Health Organization (WHO) is a specialized agency of the United Nations created in 1948 with the primary responsibility for international health matters and public health. The WHO Regional Office for Europe is one of six regional offices throughout the world, each with its own programme geared to the particular health conditions of the countries it serves. Member States Albania Andorra Armenia Austria Azerbaijan Belarus Belgium Bosnia and Herzegovina Bulgaria Croatia Cyprus Czech Republic Denmark Estonia Finland France Georgia Germany Greece Hungary Iceland Ireland Israel Italy Kazakhstan Kyrgyzstan Latvia Lithuania Luxembourg Malta Monaco Montenegro Netherlands Norway Poland Portugal Republic of Moldova Romania Russian Federation San Marino Serbia Slovakia Slovenia Spain Sweden Switzerland Tajikistan The former Yugoslav Republic of Macedonia Turkey Turkmenistan Ukraine United Kingdom Uzbekistan