1. EARS-Net data on antimicrobial resistance in Ireland Quarter 1-4 2015 31 st March 2016

2. KEY POINTS, 2015 (General) Escherichia coli The numbers of invasive E. coli infections increased since 2004 (Note: decrease in 2015 due to incomplete reporting by 3 laboratories) The proportion of ESBL-positive E. coli has stabilised since 2013 but remains at its highest level Fluoroquinolone- and aminoglycoside-resistance and multi-drug resistance showed signs of decreasing in 2015 Staphylococcus aureus/ MRSA The number and proportion of MRSA bloodstream infections decreased since 2006 Klebsiella pneumoniae ESBL-positivity and resistance to fluoroquinolones and aminoglycosides increased dramatically between 2012 and 2013 corresponding with the rise of multi-drug resistant K. pneumoniae (MDRKP) Carbapenem-resistance, particularly as a result of carbapenemase production, among K. pneumoniae is increasing Enterococcus faecium/ VREfm (vancomycin-resistant E. faecium) The numbers and proportion of VREfm bloodstream infections increased since 2004 Ireland has the highest proportion of VREfm in Europe EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015

3. KEY POINTS, 2015 Escherichia coli The proportion of patients with invasive infections caused by E. coli producing extended- spectrum beta-lactamases (ESBLs) has stabilised but remains high at 10.5% The proportion of invasive infections caused by multi-drug resistant (MDR) E. coli (displaying resistance to three or more antimicrobial classes) decreased slightly to 14.6% Staphylococcus aureus/ MRSA The proportion of S. aureus BSI that were meticillin-resistant (i.e. MRSA) decreased 18.5%, the lowest proportion to date Klebsiella pneumoniae The proportion of patients with invasive infections caused by MDR-K. pneumoniae (MDRKP) increased to 9.5% in 2015, the second highest proportion to date The proportion of patients with invasive infections caused by carbapenem-resistant K. pneumoniae isolates increased to 2.3%, the highest proportion to date Enterococcus faecium/ VREfm (vancomycin-resistant E. faecium) The proportion of E. faecium BSI that were vancomycin-resistant (i.e. VREfm) stabilised at 45.6% remaining at a high level Ireland has the highest proportion of VREfm in Europe EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015

4. EARS-Net case definition EARS-Net collects antimicrobial resistance data on the first invasive isolate (specimen types indicated below) per patient per quarter for eight key pathogens (arranged in order of frequency reported): Escherichia coli (blood or CSF) Staphylococcus aureus (blood only) Enterococcus faecium (blood only) Klebsiella pneumoniae (blood or CSF) Streptococcus pneumoniae (blood or CSF) Enterococcus faecalis (blood only) Pseudomonas aeruginosa (blood or CSF) Acinetobacter spp. (blood or CSF) EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015

5. Data collected by EARS-Net Routinely-generated data from laboratories on key antibiotics for eight pathogens under surveillance –Qualitative, i.e. RIS data (interpretations only) –Quantitative, i.e. MIC/Etest results in mg/l* *especially important for pneumococci Reference laboratory data –Serotypes on pneumococci –Carbapenemase confirmation on K. pneumoniae/E. coli isolates that are CRE EARS-Net and antimicrobial Resistance in Ireland, DIT, April 2016

6. Data Management Nationally o Data stored in WHONET format (a freeware from WHO, which is versatile for collecting, storing and analysing AMR data) and in an Access database at HPSC Locally o WHONET files* o LIMS files*, that can be translated to WHONET via BacLink software o Excel template* o Isolate Record Forms *all electronic files should be encrypted before being sent to HPSC by email EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015

7. Participation in EARS-Net Between 2007 and 2014, all laboratories (n=39) and acute hospitals (n=58) participated in EARS-Net resulting in 100% coverage of the Irish population In 2015, a number of laboratories suspended their participation due to resource issues: Midland Regional Hospital Portlaoise between Q2 and Q3 2015 Midland Regional Hospital Tullamore between Q2 and Q3 2015 Letterkenny General Hospital from Q3 2015 onwards The population coverage by EARS-Net in 2015 is estimated to be approx. 97% EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015 Note: estimated population coverage by EARS-Net in other EU/EEA countries varies considerably from <20% to 100%

8. Data Management EUCAST vs CLSI (2015) 33 labs have now adopted EUCAST guidelines = 94% of all isolates 6 labs still using CLSI Data collection (2015) WHONET – 22 labs – 86%* of data LIMS file – 2 labs – 4%* Excel – 3 labs – 3%* Paper forms – 11 labs – 6%* * Note: not 100% due to rounding! EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015

9. Escherichia coli EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015

10. Escherichia coli invasive infections *2015 data are provisional; note: missing data from 3 laboratories for 2 quarters each Extrapolated figure in 2015 accounts for missing data using data for the same time period in the previous year Key messages: The numbers of invasive E. coli infections have increased since 2004 The upward trend in proportions of 3GC-resistant and ESBL-positive E. coli have slowed down since 2013 but remain at a high level Fluoroquinolone-, aminoglycoside- and multi-drug resistance show signs of decreasing in 2015* EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015 (Extrapolated: 2796)

11. Trends in E. coli invasive infections showing percentage resistance to fluoroquinolones, aminoglycosides and 3 rd -generation cephalosporins *2015 data are provisional; note: missing data from 3 laboratories for 2 quarters each FQREC, fluoroquinolone (e.g. ciprofloxacin)-resistant E. coli; GEN, gentamicin, TOB, tobramycin; AMK, amikacin (GEN, TOB and AMK are aminoglycosides); 3GC, 3 rd -generation cephalosporins (e.g. cefotaxime, ceftazidime) EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015

12. Trends in E. coli invasive infections showing percentage 3GC- resistance and ESBL-positivity *2015 data are provisional; note: missing data from 3 laboratories for 2 quarters each 3GC, 3 rd -generation cephalosporins (e.g. cefotaxime, ceftazidime); ESBL, extended-spectrum beta-lactamase EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015

13. Map downloaded from ECDC’s TESSy database on 21/10/2015: http://ecdc.europa.eu/en/healthtopics/antimicrobial_resistance/database/Pages/database.aspx Distribution of 3 rd -generation cephalosporin resistant E. coli in EARS-Net countries in 2014 EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015 IE rank (2014; 11.6%): 13/29 Median = 11.3% Trends 12 countries 1 country

14. Trends in E. coli invasive infections with percentage multi-drug resistance *2015 data are provisional; note: missing data from 3 laboratories for 2 quarters each MDR, multidrug resistance (defined as resistance to 3 or more classes of antibiotics OR a confirmed carbapenemase producer) EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015

15. Staphylococcus aureus EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015

16. Staphylococcus aureus bloodstream infections *2015 data are provisional; note: missing data from 3 laboratories for 2 quarters each Extrapolated figure in 2015 accounts for missing data using data for the same time period in the previous year Key message: The numbers and proportion of MRSA bloodstream infections have been decreasing since 2006 EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015 (Extrapolated: 1110)

17. Trends in S. aureus bloodstream infections showing %MRSA *2015 data provisional to the end of Q4; and missing data from 3 laboratories for 2 quarters each EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015

18. Map downloaded from ECDC’s TESSy database on 21/10/2015: http://ecdc.europa.eu/en/healthtopics/antimicrobial_resistance/database/Pages/database.aspx Distribution of MRSA in EARS-Net countries in 2014 EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015 IE rank: 12/29 (19.4%) Median = 13.1% 2014 trends 2 countries 8 countries

19. Distribution of MRSA in EARS-Net countries in 2014 EARS-Net and antimicrobial Resistance in Ireland, DIT, April 2016

20. Trends in S. aureus bloodstream infections (rates) †Rate per 1,000 bed days used; *2015 data are provisional; note: missing data from 3 laboratories for 2 quarters each EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015

21. For S. aureus/MRSA data by acute hospital in Ireland, please click here here EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015

22. Klebsiella pneumoniae EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015

23. Klebsiella pneumoniae invasive infections *2015 data are provisional; note: missing data from 3 laboratories for 2 quarters each Extrapolated figure in 2015 accounts for missing data using data for the same time period in the previous year Key messages: The highest number of invasive K. pneumoniae infections were reported in 2015 ESBL-positivity and resistance to fluoroquinolones and aminoglycosides increased dramatically between 2012 and 2013 corresponding with the rise of multi-drug resistant K. pneumoniae (MDRKP) Carbapenem-resistance among K. pneumoniae, particularly as a result of carbapenemase production (see later slide), is increasing EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015 (Extrapolated: 403)

24. Trends in K. pneumoniae invasive infections showing percentage resistance to fluoroquinolones, aminoglycosides and 3 rd -generation cephalosporins *2015 data are provisional; note: missing data from 3 laboratories for 2 quarters each 3GC, 3 rd -generation cephalosporins (e.g. cefotaxime, ceftazidime); CIP, ciprofloxacin; OFX, ofloxacin (CIP and OFX are fluoroquinolones); GEN, gentamicin, TOB, tobramycin; AMK, amikacin (GEN, TOB and AMK are aminoglycosides) EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015

25. Trends in K. pneumoniae invasive infections with percentage 3GC-resistance and ESBL-positivity *2015 data are provisional; note: missing data from 3 laboratories for 2 quarters each EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015

26. Map downloaded from ECDC’s TESSy database on 21/10/2015: http://ecdc.europa.eu/en/healthtopics/antimicrobial_resistance/database/Pages/database.aspx Distribution of 3 rd -generation cephalosporin resistant K. pneumoniae in EARS-Net countries in 2014 EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015 IE rank: 21/29 (13.0%) Median = 30.7% 2014 trends 11 countries 5 countries

27. Carbapenemase-producing K. pneumoniae *2015 data are provisional; note: missing data from 3 laboratories for 2 quarters each Extrapolated figure in 2015 accounts for missing data using data for the same time period in the previous year CBP, carbapenem Key messages: In 2015, the number and proportion of carbapenem-resistant K. pneumoniae were the highest to date There were 7 confirmed carbapenemase-producing K. pneumoniae from invasive infections in 2015 compared with just 2 in 2014 and 2 in 2013 Of 15 confirmed carbapenemases (invasive) to date, 12 are OXA-48 and 3 are KPC EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015 (Extrapolated: 403)

28. Trends in carbapenemase-producing K. pneumoniae in 2014 *2015 data are provisional; note: missing data from 3 laboratories for 2 quarters each EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015

29. Map downloaded from ECDC’s TESSy database on 21/10/2015: http://ecdc.europa.eu/en/healthtopics/antimicrobial_resistance/database/Pages/database.aspx Distribution of carbapenem-resistant K. pneumoniae in EARS-Net countries in 2014 EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015 IE rank: 23/28 (0.6%) Median = 1.3% 2014 trends 7 countries 1 country

30. Trends in K. pneumoniae invasive infections with percentage multi-drug resistance *2015 data are provisional; note: missing data from 3 laboratories for 2 quarters each MDRKP, multi-drug resistance K. pneumoniae (defined as simultaneously ESBL-positive and non-susceptible to ciprofloxacin and gentamicin AND/OR a confirmed carbapenemase producer) EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015

31. Map downloaded from ECDC’s TESSy database on 21/10/2015: http://ecdc.europa.eu/en/healthtopics/antimicrobial_resistance/database/Pages/database.aspx Distribution of multi-drug resistant (MDR) K. pneumoniae in EARS-Net countries in 2014 Note: MDR defined here as combined resistance to 3GCs, fluoroquinolones and aminoglycosides EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015 IE rank: 20/29 (7.3%) Median = 16.7% 2008 data downloaded from TESSy, 31/03/2016 2014 trends 6 countries 3 countries

32. Enterococcus faecium EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015

33. Enterococcus faecium bloodstream infections *2015 data are provisional; note: missing data from 3 laboratories for 2 quarters each Extrapolated figure in 2015 accounts for missing data using data for the same time period in the previous year Key messages: The numbers of VREfm bloodstream infections have been increasing since 2004 In 2015, the proportion of VREfm bloodstream infections stabilised and remained at a high level Ireland has the highest proportion of VREfm in Europe (Extrapolated: 425) EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015

34. Trends in E. faecium bloodstream infections showing %VRE *2015 data are provisional; note: missing data from 3 laboratories for 2 quarters each VRE, vancomycin-resistant enterococcus; VREfm, vancomycin-resistant E. faecium; VSEfm, vancomycin-susceptible E. faecium EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015

35. Map downloaded from ECDC’s TESSy database on 21/10/2015: http://ecdc.europa.eu/en/healthtopics/antimicrobial_resistance/database/Pages/database.aspx Distribution of vancomycin-resistant E. faecium (VREfm) in EARS-Net countries in 2014 IE rank: 1/29 (45.1%) Median = 4.5% EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015 2014 trends 8 countries 3 countries

36. Streptococcus pneumoniae EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015

37. Streptococcus pneumoniae invasive infections *2015 data are provisional; note: missing data from 3 laboratories for 2 quarters each PSSP, penicillin-susceptible S. pneumoniae; PNSP, penicillin-non-susceptible S. pneumoniae; I, intermediate-level resistance; R, high-level resistance; NS, non-susceptible; ND, not determined Extrapolated figure in 2015 accounts for missing data using data for the same time period in the previous year Key message: The number of invasive infections due to PNSP that are HLR has decreased since 2011 (Extrapolated: 313) EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015

38. Trends in S. pneumoniae bloodstream infections showing %PNSP *2015 data are provisional; note: missing data from 3 laboratories for 2 quarters each PNSP, penicillin-non-susceptible S. pneumoniae; I, intermediate; HLR, high-level resistant PCV7 introduced Sept ‘08PCV13 introduced Dec ‘10 EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015

39. Map downloaded from ECDC’s TESSy database on 21/10/2015: http://ecdc.europa.eu/en/healthtopics/antimicrobial_resistance/database/Pages/database.aspx Distribution of penicillin-non-susceptible S. pneumoniae (PNSP) in EARS-Net countries in 2014 IE rank: 8/28 (17.7%) Median = 8.9% CAUTION: Different interpretive criteria mean some countries on this map might not be comparable (see next slide – in particular differences between scenarios A and B/C)

40. Effect of different interpretive criteria to categorise penicillin susceptibility results in pneumococci Penicillin MIC distribution: Latest CLSI non-meningitis breakpoints Penicillin MIC distribution: Latest CLSI meningitis breakpoints (same as EUCAST meningitis bps) S, ≤0.06mg/L; R, ≥0.12mg/L S, ≤2mg/L; I, 4mg/L; R, ≥8mg/L Penicillin MIC distribution: Latest CLSI oral (=old) breakpoints (similar to EUCAST non-meningitis bps) CLSI: S, ≤0.06mg/L; I, 0.12-1mg/L; R, ≥2mg/L (EUCAST: S, ≤0.06mg/L; I, 0.12-2mg/L; R, ≥4mg/L) Our current strategy (in line with most European countries) A C B

41. EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015 Pneumococcal serotypes 90% (273/304) pneumococcal isolates were serotyped in 2015 From patients aged ≥65 years the target population for the PPV23 vaccine), 69% of isolates (105 of 157) were serotypes that are included in the PPV23 vaccine From patients aged <2 years (the target population for the PCV13 vaccine), 3 of 12 isolates were serotypes covered by the vaccine, i.e. 9 were non- vaccine serotypes The most common serotypes identified were 8 † (n=28), 19A* † (n=27), 12F † (n=23), 7F* † (n=22), 3* † (n=21), 22F † (n=17), 15A (n=14), 9N † (n=13), 24F (n=12) and 35B (n=11) representing 69% of all isolates typed *PCV13 serotypes; † PPV23 serotypes Serotyping data courtesy of the Irish Pneumococcal Reference Laboratory

42. Acknowledgements All microbiology laboratories for their continued support for EARS- Net and for providing data for this report EARS-Net Steering Group Microbiology team at HPSC Irish Pneumococcal Reference Laboratory National Carbapenemase Producing Enterobacteriaceae Reference Laboratory Service (CPEaRLS) EARS-Net at ECDC, Stockholm, Sweden for providing the European data and maps EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015

43. Additional slides EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015

44. Summary of resistance trends (selected pathogens) EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015

45. Monitoring trends over time: changing epidemiology *2015 data is projected total assuming 100% coverage (instead of 97%) by laboratories EARS-Net data on Antimicrobial Resistance in Ireland, Q1-4 2015