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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
2
• Population – 8,2m
• Capital – Abu Dhabi
• Three Health Authorities: – MOH (Federal)
– HAAD (Regional)
– DHA (Regional)
Abu Dhabi
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,…
MRSA Prevalence in Japan, 1971-1995 (%)
In Japan… In the U.S. …
In Germany…
MRSA Prevalence in Germany, 1990-2010 (%)
… and many other countries
around the world…
Rising Bacterial Resistance/Decreasing Susceptibility to Common Antibiotics in Al Ain, UAE, 1999-2008
Al-Kaabi et al. EMHJ, 17:6, 2011
% Susceptible
0
10
20
30
40
50
60
70
80
90
100
1999-2002 2004 2005 2006 2007 2008
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
And the Middle East is no different…
Emergence of pan-resistant CRE in Abu Dhabi Emirate
May 2013
• 78 yr old female
• Peritonitis after re-laparotomy 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
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”
“Bacteria are starting to become so resistant to common antibiotics that it could bring about the end of modern medicine as we know it.”
„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 19th 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” “This is a global issue for governments, the medical profession, the pharmaceutical industry and individuals
Prof. Dame Sally Davies
UK Government Chief Medical Officer
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
Policy and Standards
Data and Surveillance
Systems
Education and
Awareness Other
• Educate patients and the community
• Conduct Educational Sessions for high-prescribing Physicians
• Publish articles on AMR, e.g. CD Bulletin
• Joint repository of guidelines & antibiotic stewardship
• Facilitate academic research and improve curriculum
• Advocate for AMR Surveillance Reference Laboratory
• Federal Law No. (4) 1983
• HAAD Standards/Circulars:
POM/OTC
Infection Control Management for HCFs
Monitoring and Reporting of Antimicrobial Resistance Surveillance
• Establish Antimicrobial Resistance Surveillance System (AD ARS)
• Monitor Physician prescription patterns
13
Monitoring the Burden of Antimicrobial Resistance in Abu Dhabi
The Abu Dhabi AMR 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
Abu Dhabi – Antimicrobial Resistance Surveillance Program (AD ARS)
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
E. faecalis/E. faecium E. coli K. pneumoniae
S. maltophilia
A. baumannii P. aeruginosa Shigella spp. Salmonella spp.
C. albicans M. tuberculosis H. influenzae
S. agalactiae
AD ARS allows Analysis for >350 Species, but focuses on the 17 most relevant Groups/Species (84% of isolates)
Nr. Organism N (species)
N (isolates)
% Rank
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
Susceptible Resistant
CLSI Breakpoint:
S≤2, R≥4
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
1,360,518 Antimicrobial susceptibility test results
67 Healthcare
facilities
67,501 Patients
~90,000 Specimens
from 208 Sources
73,682 bacterial/
fungal Isolates
353 different species
166 anti-microbials (25 classes)
AD ARS 2010-2012 Data base is very comprehensive: Key Figures
AD ARS Database 2010-2012
(WHONET)
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
The Microbiology Lab: A Perfect Partner for Antimicrobial Resistance Surveillance
Antimicrobial Susceptibility Testing in the Lab: Disk Diffusion Tests (Kirby-Bauer)
AD ARS is designed as a hospital laboratory- based AMR Surveillance System
AD ARS collects data on all types of Antimicrobial Susceptibility Tests (AST) conducted
• Test Result: – S – I – R, based on: – Zone diameter
(mm)
Agar Diffusion/KB MIC (Broth dilution, VITEK) E-Test
Test Result: ◦ S – I – R, based on: ◦ Minimal Inhibitory
Concentration (MIC)
Test Result: ◦ S – I – R, based on: ◦ Minimal Inhibitory
Concentration (MIC)
S = Sensitive, I = Intermediate, R = Resistant
64 32 16 8 4 2 1 .5 .25 .125 0.06 0 µg/ml
82.4% 17.2% 0.3%
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)
70.1
27.0
0.2
74.7
23.5
0.3
82.4
17.2
0.3 0
20
40
60
80
100
Broth dilution Disk diffusion E-Test
% 2010 2011 2012
Trend of Antimicrobial Susceptibility Tests (AST) conducted in %, by method, AD ARS 2010-2012
MIC (Vitek 2)
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)
• 3rd-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. faecium E. coli K. pneumoniae
S. maltophilia
A. baumannii P. aeruginosa Shigella spp. Salmonella spp.
C. albicans M. tuberculosis H. influenzae
E. faecalis
Staphylococcus aureus (2012)
Example: Staphylococcus aureus
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.
-Lactams (MRSA) 27.5% R
Fluoroquinolones: 15-28% R
Macrolides: 19.8% R
Penicillin 91.5% R
LNZ+VAN: Full Susceptible
S. aureus E. coli
K. pneumoniae Salmonella spp. P. aeruginosa
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
AD ARS allows various Breakdowns of data Here: Inpatient versus outpatient isolates
S. aureus E. coli
0
10
20
30
40
50
60
70
80
AMP CZO CXM CRO CTX CPD CXA CIP LVX MFX NOR TCY
%R Inpatient Outpatient
0
10
20
30
40
50
60
70
80
90
100
PEN OXA CIP LVX MFX SXT CLI ERY
%R Inpatient Outpatient
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
0
10
20
30
40
50
60
70
80
AMP AMC CEP CZO CXM CRO CTX CPD CXA GEN TOB CIP LVX NOR SXT MNO TCY
%R Invasive Urinary Tract
Benchmarking: AD ARS allows Inter-Facility Comparisons
28
22
27 26
22
30
36
43
29
61
28
36
24
28 27 28 27
29 30 27
0
10
20
30
40
50
60
70
Lab 1 Lab 2 Lab 3 Lab 4 Lab 5 Lab 6 Lab 7 All Labs(Average)
%R 2010 2011 2012
Staphylococcus aureus:
Trend of percentage of isolates resistant (%R) to methicillin (MRSA)
by Laboratory, AD ARS, 2012
AD ARS allows to assess the Frequency of Multidrug-Resistant (MDR) organisms
S. aureus (MDR) E. coli (MDR)
Shigella spp. (MDR) K. pneumoniae (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
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
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
No. of antimicrobial classes resistant
Isolates (N) Isolates (%)
0 6 12.2
1 6 12.2
2 15 30.6
3+ (MDR) 22 44.9
Total 49 100.0
A. baumannii (MDR) 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 (%)
0 157 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)
No. of classes resistant
No. of isolates
Predominant MDR Profile PIP TIC TCC TZP CAZ FEP ATM IPM MEM AMK GEN TOB CIP LVX MFX NOR COL MNO TCY
%
0 323 --- --- --- --- --- 13.0
1 661 --- --- --- --- --- MNO --- 26.6
2 558 --- --- IPM --- --- --- MNO --- 22.4
3 285 --- --- ATM IPM --- --- --- MNO --- 11.5
4 184 TIC TCC --- ATM --- --- --- MNO --- 7.4
5 184 PIP --- --- --- CAZ FEP --- IPM --- --- --- --- --- --- TCY 7.4
6 142 --- --- TCC TZP CAZ FEP ATM IPM MEM --- --- --- MNO --- 5.7
7 77 PIP TIC TCC --- CAZ FEP ATM IPM MEM --- --- --- MNO --- 3.1
8 55 --- --- TCC TZP CAZ FEP ATM IPM MEM AMK GEN TOB CIP --- --- --- MNO --- 2.2
9 18 PIP TIC TCC --- CAZ FEP ATM IPM MEM AMK GEN TOB CIP --- --- --- MNO --- 0.7
10 1 PIP TIC TCC --- CAZ FEP ATM IPM MEM AMK GEN TOB CIP --- --- --- COL MNO --- 0.0
Total 2,488 100.0 3+ 946 Non-susceptible to three or more classes of antimicrobial agents (MDR) 38.0
Example: Pseudomonas aeruginosa:
Percentage (%) of multidrug-resistant (MDR)
isolates, AD ARS, 2012
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
Staphylococcus aureus: Percentage of Isolates resistant to Methicillin (%R), by country, 2011
AD ARS allows to compare and benchmark local data to other regions and countries
Europe
AD ARS demonstrates high resistance rates, compared to European countries (Gram-pos.)
S. aureus: Oxacillin R S. pneumoniae: Penicillin R
S. pneumoniae: Macrolide R E. faecium: Vancomycin R
AD ARS demonstrates high resistance rates, compared to European countries (Gram-neg.)
E. coli: Fluoroquinolone R P. aeruginosa: Pip/Taz R
P. aeruginosa: Ceftazidim R E. coli: 3rd Gen. Cephalosporins R
Staphylococcus aureus: Percentage of invasive Isolates resistant to Methicillin (%R), by country, AD ARS/ECDC 2011
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
International Benchmarking enables us to set Goals and Targets…
0.3%
31.2%
54.6%
0%
10%
20%
30%
40%
50%
60%
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
% Resistant
Median: 20.1%
2 year target: Below median
5 year target: Below 10%
10 year target: Below 5%
Other Activities and Projects
HAAD is monitoring Physician Prescription Patterns for Antibiotics
Data Source: HAAD eClaim data Courtesy: Dr. Yousuf Naqvi (HAAD)
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
This GP is prescribing
Ceftriaxone
(i.v.) in 84% of all J01 patient
encounters
Physician Education
and Awareness
is Essential!
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
