Service Delivery and Safety Department World Health Organization, Headquarters

Service Delivery and Safety Department World Health Organization, Headquarters WHO global (laboratory-based) survey on multidrug-resistant organisms (MDROs) in health care PROJECT SUMMARY Given the important profile of antimicrobial resistance (AMR) within WHO, as highlighted in a recent Executive Board Resolution (EB134.R13), this survey aims to collect data on the prevalence of multidrug-resistant organisms (MDROs) from laboratories in a wide range of health-care facilities. The outcome will be a data summary and interpretation document, including information on the capacity of health-care laboratory testing. This survey is unique and is in support of the annual WHO SAVE LIVES: Clean Your Hands global campaign, with the related document being issued on the campaign celebration day of 5 May 2014. RATIONALE AND BACKGROUND INFORMATION AMR is of global concern 1. This is mainly due to the emergence, substantial rise and spread of antibiotic resistant bacteria in health-care facilities. Infections caused by drug-resistant pathogens increase mortality across all settings, and can lead to prolonged stays in hospital and increased risk of admission to intensive care units. This situation is particularly worrying since no new class of antibacterial agents has been developed in the past 25 years, thus limiting therapeutic options to treat these bacterial infections. Over the last few years, WHO regional offices and HQ have committed to take urgent action to assess the burden of AMR worldwide, lead efforts to combat AMR spread and report to Member States. Several resolutions were developed and adopted at the Regional level and a Resolution was very recently adopted by the 134 th Executive Board (EB134.R13). Every year on 5 May, since 2009, the WHO SAVE LIVES: Clean Your Hands campaign has launched a call to action to implement and sustain hand hygiene improvement worldwide, to reduce microbial transmission of health-care associated infections (HAI).The focus of the 2014 call is the role of hand hygiene in reducing the spread of AMR. Among the activities to support this call, WHO is proposing a global survey to assess and raise awareness of the burden of the five key MDROs that have been identified at the global level, as causing most colonization and infection in patients in health-care facilities. The resulting data will be unique, in that it will not only provide information on the global burden of these pathogens, but will also assess the robustness of laboratory-testing methods. For more information on WHO SAVE LIVES: Clean Your Hands and the 5 May 2014 call to action focusing on hand hygiene and AMR, visit http://www.who.int/gpsc/5may/en/. WHO is urging health-facilities to take part in this year s call to action, including the surveys proposed, to progress understanding of global AMR; information that will support everyone in their efforts to better manage patient infections and care, as well as costs. STUDY GOAL AND OBJECTIVES The main goal is to present information from a global survey on the burden of MDROs in a wide range of health-care facilities, in support of WHO s 5 May 2014 activities focused on AMR. Data will be requested from health-care facilities laboratories in all WHO regions through the WHO SAVE LIVES: Clean Your Hands campaign communications plan, as well as by gathering the support of the WHO CleanHandsNet network and other infection control networks. It is expected that participating facilities will be registered with the WHO campaign if not already

http://www.who.int/gpsc/5may/register/en/index.html. Currently, the SAVE LIVES: Clean Your Hands campaign has over 16 000 health-care facilities signed up to it, across 168 countries. The main objectives are to: 1) conduct a global survey on the burden of MDROs from clinical blood and urinary specimens routinely submitted to participating laboratories for inpatients in a wide range of health-care facilities; 2) understand the techniques used in health-care laboratories for the identification and susceptibility testing of inpatient blood and urine specimens. Data will be related to blood culture and urine (Mid-Stream Urine [MSU] and Catheter Specimen Urine [CSU] samples to assess the prevalence of five selected key MDROs: 1. Methicillin-resistant Staphylococcus aureus [MRSA]* 2. Vancomycin-resistant enterococci [VRE ]** 3. Extended-spectrum β-lactamase [ESBL] producing Enterobacteriaceae 4. Carbapenem Resistant Enterobacteriaceae [CRE], and 5. Multi-resistant Acinetobacter spp [MRAB] *MRSA Staphyloccous aureus which are resistant to methicillin/oxacillin/cefoxitin. **VRE Enterococci spp. which are resistant to glycopeptide antibiotics (i.e. vancomycin or teicoplanin). ESBL Gram-negative organisms that mediate resistance to extended-spectrum third generation cephalosporins, (e.g. ceftazidime, cefotaxime, and ceftriaxone) and monobactams (e.g. aztreonam) but do not affect cephamycins (e.g. cefoxitin and cefotetan) or carbapenems (e.g. meropenem or imipenem). 2 CRE Enterobacteriaceae that produce any β-lactamase that hydrolyses carbapenems (any or all of ertapenem, doripenem, imipenem and meropenem) and are resistant to all of the following third-generation cephalosporins: ceftriaxone, cefotaxime, and ceftazidime. 3,4 MRAB Multi-resistant Acinetobacter spp.: Isolate resistant to at least three classes of antimicrobial agents, i.e. all penicillins and cephalosporins (including inhibitor combinations), fluoroquinolones, and aminoglycosides. 5 STUDY DESIGN This is a global survey with online submission of data based on a WHO closed-question questionnaire to be completed by laboratories in health-care facilities managing inpatient blood and urine samples. Inclusion criteria: health-care settings registered for the WHO SAVE LIVES: Clean Your Hands global campaign and other WHO-associated networks, accepting to participate in the survey upon invitation. Expected duration: data collection will take place over one week between 1 March - 13 June 2014. METHODS This project is being run in collaboration with the WHO Collaborating Centre on Patient Safety at the University of Geneva Hospitals, directed by Professor Didier Pittet.

Participants will be recruited through the global call from WHO HQ, primarily through campaign email communications to the SAVE LIVES: Clean Your Hands and WHO CHN databases and stakeholders. The survey, undertaken by eligible participants, will be based on the routine, ordinary collection of clinical blood and urine (MSU & CSU) culture specimens. Invited laboratories will be asked to report the first isolate from inpatients, only during the study week proposed by WHO HQ. Surveys should be conducted in laboratories serving inpatient health-care facilities for one continuous week (7 days) from 1 March - 13 June 2014. Data should be collected by the laboratory staff during any one week identified within this time frame, and returned to WHO in a single electronic form by 15 June 2014. The name of the laboratory staff member completing the survey will be required to answer any queries, but will not be used for any other purpose. All data, including staff identity will be kept strictly confidential by WHO. Secured online data submission has been developed to support the survey and the online data collection is based on the survey questionnaire outlined in Annex 1; no modifications will be made. Confidentiality clauses are to be signed by all bodies supporting data collection, with data review only accessible to internal WHO staff with all measures available put in place to ensure data protection. Data collection, analysis, reporting and project management will be conducted by WHO in collaboration with the WHO Collaborating Centre at the University Hospitals of Geneva. WHO commits to keeping the individual facility names and data strictly confidential. Overall pooled data, with no facility identification information, will be disseminated by WHO. An example of a similar anonymous data summary document disseminated by WHO is the Summary Report of the 2011 WHO Hand Hygiene Self-Assessment Framework Global Survey, available at http://www.who.int/gpsc/5may/hhsa_framework/en/index.html. The survey will be available in English, French and Spanish CONFIDENTIALITY This survey will be conducted through a secure online data submission system using Datacol at WHO. The system generates a personalized link connected to the email of the person invited by WHO to participate. Health-care facilities registered for WHO SAVE LIVES: Clean Your Hands and other WHO-associated networks will be invited to participate by a personalized invitation email explaining the aim of the survey, providing instructions and a unique link automatically generated by the platform. The invitation email will be sent from the WHO SAVE LIVES: Clean Your Hands email address (savelives@who.int). In all cases, WHO commits to keeping the individual facility names and results strictly confidential. SAFETY CONSIDERATIONS Any serious concerns that arise from the laboratories reports will be addressed through the WHO report including recommendations on how antimicrobial resistance reporting can be improved. FOLLOW-UP The WHO Clean Care is Safer Care team in collaboration with the WHO Collaborating Centre on Patient Safety will follow up the survey for its duration, by answering enquiries sent by participants to the WHO email address dedicated to the WHO SAVE LIVES: Clean Your Hands campaign (savelives@who.int), and sharing and collaborating with any survey coordinators. Furthermore, after data collection, if appropriate, the WHO Clean Care is Safer Care team will

discuss results to identify best strategies for recommendations to health-care facilities in the perspective of further laboratory testing improvements. DATA MANAGEMENT AND STATISTICAL ANALYSIS Data will be analyzed by the WHO Collaborating Centre on Patient Safety, in collaboration with the WHO Clean Care is Safer Care team. Detailed and summary descriptive analysis by country and region will be performed. Results will not be given by facility in order to avoid any identification. As for previous similar WHO ERC-approved surveys, results will be summarized by country only when at least ten health care facilities have submitted their results (see Summary Report of the 2011 WHO Hand Hygiene Self-Assessment Framework Global Survey at http://www.who.int/gpsc/5may/hhsa_framework/en/index.html). EXPECTED OUTCOMES OF THE STUDY A summary results report will be issued on the WHO web site featuring anonymised, collated data by WHO region and country, if possible. Based on the results, important information will be highlighted with regards to MDROs occurring in a wide range of acute health-care facilities, as well as laboratory methods/capabilities. ETHICS Given that neither patients nor health-care workers are involved, there are no main ethics considerations arising from this project. Regarding data management, health-care facilities are assured that confidentiality will be maintained regarding their identity. No informed consent is, therefore, required for this survey. QUALITY ASSURANCE Since data will be collected only through the forms submitted by laboratory personnel across the world, variations in laboratory methods used to identfy MDROs are expected, based on the resources and facilities available. For this reason, the questions regarding laboratory methods included in the survey will allow WHO to have an insight into the level of data quality, although quality assurance during the survey is not seen as the overall aim. PROJECT MANAGEMENT Prof. Benedetta Allegranzi, principal investigator, Service Delivery and Safety, World Health Organization, HQ, Geneva, Switzerland. Prof. Didier Pittet, co-investigator, data analysis, WHO Collaborating Centre on Patient Safety, University of Geneva Hospitals, Geneva, Switzerland. Dr Nizam Damani, co-investigator, survey designer and lead data reporter, Service Delivery and Safety, World Health Organization, HQ, Geneva, Switzerland. Ms Claire Kilpatrick and Dr Zeynep Kubilay, co-investigators, survey promotion and communications and recruitment activities, Service Delivery and Safety, World Health Organization, HQ, Geneva, Switzerland. REFERENCES 1. WHO: The evolving threat of antimicrobial resistance:options for action. Geneva: World Health Organization, 2012. 2. CDC Laboratory detection of Extended -spectrum β lactamsases (ESBL). Access on 15tth January 2014. http://www.cdc.gov/hai/settings/lab/lab_esbl.html 3. CDC Tool kit. Guidance for Control of Carbapenem-resistantEnterobacteriaceae. Atlanta: CC, 2012. 4. UK Health Protection Agency. Laboratory detection and reporting of bacteria with carbapenem-hydrolysing β-lactamases (carbapenemases). London: Health Protection Agency, 2013. 5. Multidrug-resistant, extensively drug-resistant and pan drug-resistant bacteria: an international expert proposal for interim standard. definitions for acquired resistance. Clin Microbiol Infect 2012; 18: 268 281.

Annex 1 WHO global (laboratory-based) survey on multidrug-resistant organisms (MDROs) in health care DATA COLLECTION FORM Duration of survey: Any one continuous week between 1 March - 13 June 2014 Name of the acute health-care facility Name of the laboratory City Postcode Country Laboratory staff member completing the survey Surname (Capital letter) First name (Capital letter) Email Type of acute health-care facility Public Private Not-for-profit General Teaching Other.. Total number of acute care inpatient beds in the facility: 200 201-500 501-1000 1000 Is the facility registered for WHO SAVE LIVES: Clean Your Hands (http://www.who.int/gpsc/5may/en/index.html)? Is a Clinical Microbiologist employed in the laboratory service?

CLINICAL LABORATORY ISOLATES FROM BLOOD AND URINE CULTURES OVER A ONE WEEK PERIOD Instructions for completion Complete this form with data related to ONE CONTINUOUS WEEK between 1 March -13 June 2014 Include only first isolate from inpatients during the study week. For urine, use both Midstream and Catheter Specimens (MSU, CSU). Dates of survey period: from... to.... Total no. of blood cultures set (aerobic & anaerobic) processed per year (approx.) Total no. of blood cultures set (aerobic & anaerobic) processed during the week of the survey.. Total no. of inpatient urine specimens processed per year (approx.)..... Total no. of inpatient urine specimens processed during the week of the survey. Positive blood cultures (survey week) Positive urine cultures (survey week) Total no. of all Gram positive microorganisms identified Total no. of Staphylococcus aureus No. of MRSA Total no. of Enterococci spp No. of VRE Total no. of all Gram negative microorganisms identified Total no. of Enterobacteriaceae spp Total no.of E.coli No.of ESBL E.coli No.of CRE E.coli Total no.of Klebsiella spp No.of ESBL Klebsiella spp

No.of CRE Klebsiella spp. No.of ESBL other in Enterobacteriaceae spp. (excluding E.coli and Klebsiella spp) No.of CRE in other Enterobacteriaceae spp (excluding E.coli and Klebsiella spp) Total no. of Acinetobacter spp No.of multidrug resistant Acinetobacter spp Total no. of fungi (including yeast) Total no. of other non-bacterial, non fungal species LABORATORY IDENTIFICATION OF MDROs Identification of Staphylococcus aureus Gram stain Slide or Tube coagulase Non-automated method If yes, state the method (API etc.) :.... Automated method If yes, state the method (Vitek, Phoenix, MALDI-TOF etc): Other identification methods: (molecular & non-molecular):. Identification of Enterococcus spp Gram stain Streptococcal Lancefeild grouping Non-automated method

If yes, state the method (API etc.) :.. Automated method If yes, state the method (Vitek, Phoenix, MALDI-TOF etc): Other identification methods: (molecular & non-molecular):. Identification of Enterobacteriaceae spp Gram stain Chromogenic Agar If yes, manufacturer s name... Non-automated method If yes, state the method (API etc.) :.. Automated method If yes, state the method (Vitek, Phoenix, MALDI-TOF etc): Other identification methods: (molecular & non-molecular):.. LABORATORY CONFIRMATION OF RESISTANCE Which antibiotic interpretative criteria is used for disc diffusion, break point and MIC (Minimum Inhibitory Concentration) in your laboratory? CLSI EUCAST BSAC Other :..

MRSA (Methicillin-resistant Staphycoccus aureus) Disc diffusion method If Yes, which antibiotic disc is used? Methicillin 10μg Oxacillin 1μg Cefoxitin 10μg Cefoxitin 30μg E test MIC (Broth method or agar dilution) Non-automated susceptibility testing method If yes, state the method.. Automated susceptibility testing method If yes, state the method (Vitek, Phoenix etc.)... Other methods: (molecular & non-molecular):. VRE (Vancomycin-resistant enterococci) Disc diffusion method If Yes, which antibiotic disc is used: Vancomycin 5 μg Vancomycin 30 μg Teicoplanin 30 μg

E test MIC (Broth method or agar dilution) Non-automated susceptibility testing method If yes, state the method.. Automated susceptibility testing method If yes, state the method (Vitek, Phoenix etc.)... Other methods: (molecular & non-molecular):. ESBL (Extended-Spectrum Beta-Lactamase) Presence of an ESBL is confirmed by : Chromogenic ESBL agar If yes, manufacturer s name... ESBL combi-discs If yes, manufacturer s name... Disc approximation ESBL E-tests MIC (Broth method or agar dilution) for 3 rd generation cephalosporins Non-automated susceptibility testing method If yes, state the method.. Automated susceptibility testing method

If yes, state the method (Vitek, Phoenix etc.)... Other methods: (molecular & non-molecular):. CRE (Carbapenem Resistant Enterobacteriaceae) Presence of CPE is confirmed by: Chromogenic CPE agar If YES, product and manufacturer s name.. Modified Hodge Test MIC (Broth method or agar dilution) for Carbapenems Non-automated susceptibility testing method If yes, state the method.. Automated susceptibility testing method If yes, state the method (Vitek, Phoenix etc.)... Other methods: (molecular & non-molecular):. LABORATORY QUALITY CONTROL Agar plates used in the laboratory are : Purchased pre-poured media Prepared in the laboratory If prepared in the laboratory, do you quality control your media?

Quality control organisms used or susceptability in your laboratory testing MRSA NO ATCC NCTC other If other, please specify... VRE NO ATCC NCTC other If other, please specify. CRE NO ATCC NCTC other If other, please specify... ESBL NO ATCC NCTC other If other, please specify... Does your laboratory participate in the External Quality Control Scheme? YES NO Does your country have a Reference Laboratory to confirm CRE and other multidrug-resistant organisms? Don't know Additional comments WHO thanks you very much for your contribution to this important global survey in support of the SAVE LIVES: Clean Your Hands 5 May 2014 call to action.