The Abu Dhabi Antimicrobial Resistance Surveillance Program (AD ARS)

The Abu Dhabi Antimicrobial Resistance Surveillance Program (AD ARS) Dr. med. Jens Thomsen MPH Section Head, Occupational and Environmental Health Community Health & Surveillance Dept. Public Health and Research Division Health Authority Abu Dhabi United Arab Emirates International Conference on Antimicrobial Stewardship December 1-2, 2013, King Fahad Medical City, Riyadh, KSA

United Arab Emirates Abu Dhabi Population 8,2m Capital Abu Dhabi Three Health Authorities: MOH (Federal) HAAD (Regional) DHA (Regional) 2

Health Authority Abu Dhabi (HAAD) 3

The Success Story of Antimicrobial Agents has begun only 85 years ago 1928: Dr. Alexander Fleming discovers Penicillin

and Dr Fleming already warned in 1945 about the risk of resistance development Nobel Lecture, Dec 11, 1945, Stockholm 5

Of course it happened, globally, In Japan In the U.S. MRSA Prevalence in Japan, 1971-1995 (%) In Germany and many other countries around the world MRSA Prevalence in Germany, 1990-2010 (%)

And the Middle East is no different % Susceptible 100 Rising Bacterial Resistance/Decreasing Susceptibility to Common Antibiotics in Al Ain, UAE, 1999-2008 90 80 70 60 50 40 30 20 10 S. aureus OXA-S P. aeruginosa PIP/TAZ-S P. aeruginosa IMI-S P. aeruginosa CEFTAZ-S P. aeruginosa CEFOTAX-S P. aeruginosa AMOX/CLAV-S P. aeruginosa SXT-S E. coli CEFOTAX-S E. coli CIPRO-S S. maltophilia SXT-S 0 1999-2002 2004 2005 2006 2007 2008 Al-Kaabi et al. EMHJ, 17:6, 2011

Emergence of pan-resistant CRE in Abu Dhabi Emirate May 2013 78 yr old female Peritonitis after relaparotomy due to anastomotic leak Transferred from UAQ Dubai AD hospital (!) Pan-resistant K. pneumoniae (CRE) identified from blood culture and abdominal fluid Outcome: Patient died Two other patients with same pan-resistant CRE profile (one of them died)

WHO call for action Bacteria are starting to become so resistant to common antibiotics that it could bring about the end of modern medicine as we know it. Margaret Chan, Director General, World Health Organization (WHO) March 2012 Due to misuse we are losing our first-line antibiotics and every antibiotic ever developed is at risk of becoming obsolete, as the world could be entering a Post-Antibiotic Era

UK Medical Chief: Antibiotics resistance as big a risk as terrorism A ticking time bomb If we don t take action now, then we may all be back in an almost 19 th Century environment where infections kill us as a result of routine operations We re beginning to see in some hospitals, patients coming in with this infection with no antibiotic that can be used to treat them Prof. Dame Sally Davies UK Government Chief Medical Officer This is a global issue for governments, the medical profession, the pharmaceutical industry and individuals BBC, March 12 2013

WHO Policy Package to combat Antimicrobial Resistance (2011)

HAAD has a comprehensive Strategy to combat Antimicrobial Resistance in Abu Dhabi Emirate Federal Law No. (4) 1983 HAAD Standards/Circulars: POM/OTC Infection Control Management for HCFs Monitoring and Reporting of Antimicrobial Resistance Surveillance Policy and Standards Data and Surveillance Systems Establish Antimicrobial Resistance Surveillance System (AD ARS) Monitor Physician prescription patterns Educate patients and the community Conduct Educational Sessions for highprescribing Physicians Publish articles on AMR, e.g. CD Bulletin Education and Awareness Other Joint repository of guidelines & antibiotic stewardship Facilitate academic research and improve curriculum Advocate for AMR Surveillance Reference Laboratory

Monitoring the Burden of Antimicrobial Resistance in Abu Dhabi The Abu Dhabi AMR Surveillance Program (AD ARS) 13

Abu Dhabi Antimicrobial Resistance Surveillance Program (AD ARS) Rationale In 2010 no AMR surveillance program was existing for Abu Dhabi (or on UAE level) Aim Establish a Hospital Laboratory-based Antimicrobial Resistance Surveillance Program for Abu Dhabi Emirate Objectives Collect and analyze AMD data from HCFs Systematically & continuously Report levels and trends of antimicrobial resistance Support other AMR prevention and control strategies/initiatives: Awareness and education Policies and standards Clinical care pathways, antimicrobial stewardship programs

June 2010: HAAD established the AD ARS Working Group Nr. Organisation Name Function 1. HAAD Dr. Jens Thomsen Section Head OEH, Chair AD ARS Working Group 2. Dr. Mariam Almulla Regional Officer, Communicable Diseases 3. Dr. Yousuf Naqvi Officer Vaccines & Biologicals, Pharma & Medicines Dept. 4. Dr. Sahar Fahmi Officer Pharmacovigilance/RDU 5. Dr. Bashir Aden Sr. Officer Surveillance 6. SEHA Health Services Co. Imran Iqbal Application Specialist HIS 7. Wissam Khaiwi Application Specialist - Pathology HIS 8. Kapil Dayal Head, Configuration 9. Tawam Hospital Dr. Waheed Tariq Consultant Clinical Microbiologist 10. Mohamad Baraa Section Head Microbiology 11. Rayhan Hashmey Sr. Consultant ID 12. Al Ain Hospital Dr. Farrukh Sheikh Clinical Microbiologist 13. Ms. Amna Jaffal Section Head Microbiology 14. SKMC Dr. Stefan Weber Consultant Clinical Microbiologist 15. Dr. Martin Pitout Consultant Clinical Microbiologist 16. Adeel Butt Chair, Dept. of Medicine 17. Al Mafraq Hospital Dr. Safinaz Girgis Microbiology Specialist, Deputy Chief of Microbiology 18. Ali Abdullah Senior Lab Technologist 19. Al Rahba Hospital Dr. Ragaa Y. Abbas Microbiologist 20. Corniche Hospital Dr. Judy Lee Chief Medical Officer 21. Bassam Al Sayad Chief Operating Officer 22. Al Gharbia Hospitals Maryam Aly Elsayed Laboratory Pathologist 23. Moawia Sulaiman Senior Medical Lab Technologist Microbiology 24. Cleveland Clinic AD Peter Anderson Director Laboratory Dept. 25. Rania El Lababidi Training Manager, Pharmacy Dept. 26. Shafi Mohammed Lead Infection Control Practitioner 27. UAE University Prof. Tibor Pal Professor of Microbiology, Consultant Clinical Microbiologist 28. Dr. Agnes Sonnevend Assistant Professor, Consultant Clinical Microbiologist

July 2011: HAAD issued a Standard mandating Monitoring and Reporting of AMR Data in Abu Dhabi Emirate HAAD Standard Monitoring and Reporting of Antimicrobial Resistance Mandates monitoring and reporting of antimicrobial resistance for all hospitals (n=34) and laboratories in Abu Dhabi Emirate Specifies data requirements and reporting mechanisms Regulatory instrument to establish the AD AMR Surveillance Program Issued July 2011 16

17 Relevant Organisms are under Surveillance S. aureus CNS S. pneumoniae S. pyogenes S. agalactiae E. faecalis/e. faecium E. coli K. pneumoniae Salmonella spp. Shigella spp. P. aeruginosa A. baumannii S. maltophilia H. influenzae M. tuberculosis C. albicans

AD ARS allows Analysis for >350 Species, but focuses on the 17 most relevant Groups/Species (84% of isolates) Nr. Organism N N % Rank (species) (isolates) 1. Escherichia coli 1 16,811 22.8 1 2. Staphylococcus aureus 1 9,661 13.1 2 3. Pseudomonas aeruginosa 1 6,504 8.8 3 4. Klebsiella pneumoniae 1 5,931 8.1 4 5. Coagulase-neg. staphylococci (CNS) 19 5,740 7.8 5 6. Streptococcus agalactiae (GBS) 1 5,441 7.4 6 7. Enterococcus faecalis/faecium 2 2,284 3.1 7 8. Haemophilus influenzae 1 1,696 2.3 8 9. Acinetobacter baumannii 1 1,660 2.3 9 10. Streptococcus pyogenes (GAS) 1 1,588 2.2 10 11. Streptococcus pneumoniae 1 1,464 2.0 11 12. Mycobacterium tuberculosis complex 8 886 1.2 12 13. Candida albicans 1 773 1.0 13 14. Stenotrophomonas maltophilia 1 565 0.8 14 15. Candida species (non-albicans) 15 495 0.7 15 16. Salmonella spp. 8 455 0.6 16 17. Shigella species 4 92 0.1 17 Subtotal 67 62,046 84.2 Other bacterial/fungal species 286 11,620 15.8 Total 353 73,666 100.0

The Abu Dhabi Antimicrobial Resistance Surveillance (AD ARS) System and Network

AD ARS 2010-2012 Data base is highly representative for AD Emirate: Covers all regions of the Emirate, including 67 SEHA Healthcare facilities 12 Hospitals in all three regions 55 associated health centers 66.2% of total Abu Dhabi bed capacity 73.2% of all AD clinical/patient encounters

Abu Dhabi ARS uses BacLink/WHONET 5.6 WHONET www.whonet.org/dnn Affiliations: WHO, ECDC, CLSI, APUA Managed by: Harvard Medical School and Brighams Hospital, Boston, USA Technical and strategic support for 1200 laboratories in 90 countries worldwide WHONET & BacLink Software

Using WHONET 5.6 for AMR Surveillance Example: Staph. aureus Select type of analysis & Antimicrobials Select organism of interest Select data file (time period)

Using WHONET 5.6 for AMR Surveillance Example: Staph. aureus

Using WHONET 5.6 for AMR Surveillance Example: Staph. aureus

Using WHONET 5.6 for AMR Surveillance Example: Staph. aureus MIC distribution CLSI Breakpoint: S 2, R 4 Susceptible Resistant

Using WHONET 5.6 for AMR Surveillance Example: Staph. aureus Scatterplot analysis

Using WHONET 5.6 for AMR Surveillance Exclusion of duplicate/copy strains from Analysis

AD ARS 2010-2012 Data base is very comprehensive: Key Figures AD ARS Database 2010-2012 (WHONET) 166 antimicrobials (25 classes) 67 Healthcare facilities 67,501 Patients 353 different species 1,360,518 Antimicrobial susceptibility test results 73,682 bacterial/ fungal Isolates ~90,000 Specimens from 208 Sources

AD ARS could report data each year on more clinical isolates from one Emirate only, than has been published in the scientific literature for all GCC countries combined during 21 years! All GCC countries, 1990-2011: 37,295 published isolates UAE: 491 isolates only (1.3%) Abu Dhabi ARS 2012: 50,067 isolates >100 times more data than published in 21 yrs. for UAE Ary & Balkhy, ARIC, 2012 29

AD ARS is designed as a hospital laboratorybased AMR Surveillance System The Microbiology Lab: A Perfect Partner for Antimicrobial Resistance Surveillance Antimicrobial Susceptibility Testing in the Lab: Disk Diffusion Tests (Kirby-Bauer)

AD ARS collects data on all types of Antimicrobial Susceptibility Tests (AST) conducted 64 32 16 8 4 2 1.5.25.125 0.06 0 µg/ml MIC (Broth dilution, VITEK) Agar Diffusion/KB E-Test 82.4% 17.2% 0.3% Test Result: S I R, based on: Minimal Inhibitory Concentration (MIC) Test Result: S I R, based on: Zone diameter (mm) Test Result: S I R, based on: Minimal Inhibitory Concentration (MIC) S = Sensitive, I = Intermediate, R = Resistant

AD ARS Results & Findings AD ARS Report 2012: Key Results and Findings

AD ARS Results: MIC test is more and more replacing the disk diffusion test (Kirby Bauer) Trend of Antimicrobial Susceptibility Tests (AST) conducted in %, by method, AD ARS 2010-2012 % 2010 2011 2012 100 80 70.1 74.7 82.4 60 40 20 0 27.0 23.5 17.2 0.2 0.3 Broth MIC (Vitek dilution 2) Disk diffusion E-Test 0.3

Abu Dhabi AMR Surveillance Report 2012 Key Findings High levels of antimicrobial resistance, e.g. MRSA 27.7 % S. pneumoniae/penicillin R: 12.9 % S. pneumoniae/erythromycin R: 41.2 % E. faecium/vancomycin R (VRE): 20.0 % E. coli/ciprofloxacin R: 32.5 % P. aeruginosa/pip-taz: 19.0 % A. baumannii/carbapenems R: >50 % Increasing trends of resistance, e.g. Fluoroquinolones (S. aureus, E. coli, K. pneumoniae, Salmonella spp., P. aeruginosa) 3 rd -generation Cephalosporins (E. coli, K. pneumoniae) Macrolides & Lincosamides (S. agalactiae) AMC, Gentamicin, SXT, Tetracycline (H. influenzae) High prevalence of Multidrug-resistance (3+), e.g. P. aeruginosa 24.1 % A. baumannii 53.1 % Emerging new threats CRE: Carbapenem-resistant Enterobacteriaceae Pan-resistant Enterobacteriaceae (K. pneumoniae)

AD ARS documents local Resistance Levels for each Organism under Surveillance S. aureus CNS S. pyogenes S. agalactiae E. faecalis E. faecium E. coli K. pneumoniae Salmonella spp. Shigella spp. P. aeruginosa A. baumannii S. maltophilia H. influenzae M. tuberculosis C. albicans

Example: Staphylococcus aureus Penicillin 91.5% R Staphylococcus aureus (2012) -Lactams (MRSA) 27.5% R Fluoroquinolones: 15-28% R Macrolides: 19.8% R LNZ+VAN: Full Susceptible PEN=Penicillin, OXA=Oxacillin, GEN=Gentamicin, RIF=Rifampicin, CIP=Ciprofloxacin, LVX=Levofloxacin, MFX=Moxifloxacin, SXT=Trimethoprim/Sulfamethoxazole, FOS=Fosfomycin, CLI=Clindamycin, ERY=Erythromycin, LNZ=Linezolid, VAN=Vancomycin. MIC data, error bars represent 95% confidence intervals.

AD ARS creates Baselines and monitors Local Trends of Antimicrobial Resistance S. aureus E. coli K. pneumoniae Salmonella spp. P. aeruginosa

Resistance to Fluoroquinolones is increasing across five different Species S. aureus E. coli K. pneumoniae Salmonella spp. P. aeruginosa

AD ARS allows various Breakdowns of data Here: Inpatient versus outpatient isolates S. aureus E. coli %R 100 Inpatient Outpatient %R 80 Inpatient Outpatient 90 70 80 70 60 60 50 50 40 40 30 20 30 20 10 10 0 PEN OXA CIP LVX MFX SXT CLI ERY 0 AMP CZO CXM CRO CTX CPD CXA CIP LVX MFX NOR TCY

AD ARS allows various Breakdowns of data Here: Invasive versus Non-invasive isolates Invasive Isolates tend to be more resistant than non-invasive (here: urinary tract) isolates. Example: E. coli %R 80 70 60 50 40 30 20 10 Invasive Urinary Tract 0 AMP AMC CEP CZO CXM CRO CTX CPD CXA GEN TOB CIP LVX NOR SXT MNO TCY

Benchmarking: AD ARS allows Inter-Facility Comparisons Staphylococcus aureus: Trend of percentage of isolates resistant (%R) to methicillin (MRSA) by Laboratory, AD ARS, 2012 %R 2010 2011 2012 70 60 61 50 43 40 36 36 30 20 28 22 24 30 28 27 28 22 29 27 29 27 28 30 26 27 10 0 Lab 1 Lab 2 Lab 3 Lab 4 Lab 5 Lab 6 Lab 7 All Labs (Average)

AD ARS allows to assess the Frequency of Multidrug-Resistant (MDR) organisms S. aureus (MDR) E. coli (MDR) No. of antimicrobial classes resistant Isolates (N) Isolates (%) 0 162 6.7 1 982 40.4 2 694 28.5 3+ (MDR) 595 24.5 Total 2,433 100.0 K. pneumoniae (MDR) No. of antimicrobial classes resistant Isolates (N) Isolates (%) 0 1,500 64.1 1 224 9.6 2 109 4.7 3+ (MDR) 508 21.7 Total 2,341 100.0 P. aeruginosa (MDR) No. of antimicrobial classes resistant Isolates (N) Isolates (%) 0 1,019 41.1 1 521 21.0 2 342 13.8 3+ (MDR) 596 24.1 Total 2,478 100.0 No. of antimicrobial classes resistant Isolates (N) Isolates (%) 0 1,732 26.9 1 929 14.4 2 1,133 17.6 3+ (MDR) 2,642 41.1 Total 6,436 100.0 Shigella spp. (MDR) No. of antimicrobial Isolates (N) Isolates (%) classes resistant 0 6 12.2 1 6 12.2 2 15 30.6 3+ (MDR) 22 44.9 Total 49 100.0 A. baumannii (MDR) No. of antimicrobial Isolates (N) Isolates (%) classes resistant 0 157 25.3 1 97 15.6 2 37 6.0 3+ (MDR) 329 53.1 Total 620 100.0

AD ARS allows to assess Multidrug- Resistance Patterns (MDR, XDR, PDR) Example: Pseudomonas aeruginosa: Percentage (%) of multidrug-resistant (MDR) isolates, AD ARS, 2012 No. of classes resistant No. of isolates 0 323 1 661 2 558 3 285 4 184 5 184 6 142 7 77 8 55 9 18 10 1 Predominant MDR Profile PIP TIC TCC TZP CAZ FEP ATM IPM MEM AMK GEN TOB CIP LVX MFX NOR COL MNO TCY --- --- --- --- --- --- --- --- --- --- MNO --- --- --- IPM --- --- --- MNO --- --- --- ATM IPM --- --- --- MNO --- TIC TCC --- ATM --- --- --- MNO --- PIP --- --- --- CAZ FEP --- IPM --- --- --- --- --- --- TCY --- --- TCC TZP CAZ FEP ATM IPM MEM --- --- --- MNO --- PIP TIC TCC --- CAZ FEP ATM IPM MEM --- --- --- MNO --- --- --- TCC TZP CAZ FEP ATM IPM MEM AMK GEN TOB CIP --- --- --- MNO --- PIP TIC TCC --- CAZ FEP ATM IPM MEM AMK GEN TOB CIP --- --- --- MNO --- PIP TIC TCC --- CAZ FEP ATM IPM MEM AMK GEN TOB CIP --- --- --- COL MNO --- Total 2,488 100.0 3+ 946 Non-susceptible to three or more classes of antimicrobial agents (MDR) 38.0 % 13.0 26.6 22.4 11.5 7.4 7.4 5.7 3.1 2.2 0.7 0.0

AD ARS allows Identification of MDRO- Clusters and Outbreak Analysis Methodology: WHONET-SatScan. See also: Stelling J. et al. Epidemiol Infect (2010); 138, 873-883 Huang S et. al. PLoS Medicine (2010); vol. 7, issue 2

AD ARS allows to compare and benchmark local data to other regions and countries Staphylococcus aureus: Percentage of Isolates resistant to Methicillin (%R), by country, 2011 Europe

AD ARS demonstrates high resistance rates, compared to European countries (Gram-pos.) S. aureus: Oxacillin R S. pneumoniae: Penicillin R E. faecium: Vancomycin R S. pneumoniae: Macrolide R

AD ARS demonstrates high resistance rates, compared to European countries (Gram-neg.) E. coli: Fluoroquinolone R P. aeruginosa: Pip/Taz R E. coli: 3 rd Gen. Cephalosporins R P. aeruginosa: Ceftazidim R

International Benchmarking enables us to set Goals and Targets Staphylococcus aureus: Percentage of invasive Isolates resistant to Methicillin (%R), by country, AD ARS/ECDC 2011 % Resistant 60% 54.6% 50% 40% 30% 20% 10 year target: Below 5% Median: 20.1% 5 year target: Below 10% 2 year target: Below median 31.2% 10% 0% 0.3% NO SE DK NL EE IS LT SL AT LV UK CZ DE BE FR LU BG ES IE PL SK HU AD IT EL CY MT RO PT AD=Abu Dhabi, AT=Austria, BE=Belgium, BG=Bulgaria, CY=Cyprus, CZ=Czech Republic, DE=Germany, DK=Denmark, EE=Estonia, EL=Greece, ES=Spain, FI=Finland, FR=France, HU=Hungary, IE=Ireland, IS=Iceland, IT=Italy, LT=Lithuania, LU=Luxembourg, LV=Latvia, MT=Malta, NL=Netherlands, NO=Norway, PL=Poland, PT=Portugal, RO=Romania, SE=Sweden, SL=Slovenia, SK=Slovakia, UK=United Kingdom

Other Activities and Projects

HAAD is monitoring Physician Prescription Patterns for Antibiotics Antibiotic Prescription data for Group J01 (Antibacterials for systemic Use) By Healthcare Facility and Individual Physician (GP), Abu Dhabi Emirate, 2010 This GP is prescribing a systemic antibacterial in 64% of all patient encounters Physician Education and Awareness is Essential! This GP is prescribing Ceftriaxone (i.v.) in 84% of all J01 patient encounters Data Source: HAAD eclaim data Courtesy: Dr. Yousuf Naqvi (HAAD)

A comprehensive AMR Surveillance Report is under development Draft Report on 2010-2012 AMR data is under expert review Expected to be published Q1 2014

Summary & Conclusions 1. Increasing antimicrobial resistance is a global and local problem 2. HAAD has adopted a comprehensive Strategy to control Antimicrobial Resistance Development and Spread and developed AD ARS (at no costs) 3. AD ARS allows to monitor local levels and trends of AMR and supports detection of MDRO clusters/outbreaks 4. Preliminary results demonstrate 1. Unacceptably high AMR levels 2. Increasing trends of resistance 3. High prevalence of multidrug-resistant organisms 4. Emerging new threats (CRE and pan-resistant pathogens) 5. Further action on all levels is needed to reverse increasing AMR trends 6. Health Authority Abu Dhabi would be pleased to participate in a coordinated UAE- or even GCC-wide AMR Surveillance Program

No Action today No Cure tomorrow! Dr. Jens Thomsen jthomsen@haad.ae Phone: +971 50 4193 467 53