EARS Net Report, Quarter

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EARS Net Report, Quarter 4 213 March 214 Key Points for 213* Escherichia coli: The proportion of patients with invasive infections caused by E. coli producing extended spectrum β lactamases (ESBLs) increased further to 1.4% [Figure 1] and the proportion of BSI caused by multi drug resistant (MDR; displaying resistance to three or more antimicrobial classes) E. coli increased further to 14. [Figure 4] Staphylococcus aureus: The proportion of S. aureus BSI that were meticillin resistant (i.e. MRSA) decreased further to 2.3% [Figure 5] Enterococcus faecium: The proportion of E. faecium BSI that were vancomycin resistant (i.e. VREfm) decreased to 43.1%. However, Ireland remains the only EU country with a VREfm proportion in excess of [Figure 7] Klebsiella pneumoniae: The proportion of patients with invasive infections caused by K. pneumoniae producing extended spectrum β lactamases (ESBLs) increased to 18.4%, which is over double what it was in 212 (8.8%) [Figure 13] The proportion of patients with invasive infections caused by K. pneumoniae belonging to a particular MDR profile, or MDRKP phenotype, which exhibits ESBL production and non susceptibility to both ciprofloxacin and gentamicin, increased to 12.3%. This reflects a dramatic increase when compared with 21, when only 2.2% of invasive K. pneumoniae infections belonged to this strain [Figure 19] Full participation by all 41 microbiology laboratories serving all acute hospitals in the Republic of Ireland resulting in 1% coverage of the population * 213 data provisional to the end of Q4 Background The European Antimicrobial Resistance Surveillance System (EARSS) was established in 1999 in response to the growing threat of antimicrobial resistance in Europe. In January 21, EARSS was taken over by the European Centre for Disease Control (ECDC) becoming the European Antimicrobial Resistance Surveillance Network (EARS Net). EARS Net comprises a network of over 9 microbiological laboratories serving over 15 hospitals in 3 countries that collects routinely generated antimicrobial susceptibility testing data on invasive infections caused by eight important bacterial pathogens: Escherichia coli Staphylococcus aureus Enterococcus faecium Enterococcus faecalis Klebsiella pneumoniae Streptococcus pneumoniae Pseudomonas aeruginosa Acinetobacter spp. Since 21, all laboratories (41 as of Jan 212) serving all acute hospitals (47 public and 12 private) in the Republic of Ireland participate in EARS Net representing 1% coverage of the population. Results Summaries of the annual (26 213) and quarterly (Q1 212 Q4 213) data submitted on all pathogens are shown in Tables 1 and 2, respectively. Table 3 shows a summary of the key resistance data by pathogen and HSE Area for 213. Data correct as of 3/3/214 Report produced by the Irish EARS Net Steering Group with special thanks to all the participating laboratories for their continued support and commitment to this surveillance system Health Services Executive (HSE) Health Protection Surveillance Centre (HPSC) 25 27 Middle Gardiner Street Dublin 1, Ireland +353 1 876 53 www.hpsc.ie Page 1 of 18

Table 1. Summary of EARS Net data by pathogen and year (data correct as of 3/3/214) Pathogen 26 27 28 29 21 211 212 213** Number laboratories by year end 42 44 42 43 4 41 41 41 E. coli 1656 1785 1926 264 217 221 245 2526 %Ampicillin R* 7.7 68.3 7.4 68.7 68.4 71.9 69.6 7.9 %3GC R* 4.2 6.7 7.4 7.5 8.3 9.3 1.8 12.7 %ESBL producers* 2.5 4.1 5. 5.8 6.1 7.5 8.8 1.4 %Ciprofloxacin R* 21.5 22.1 23.3 22.3 23.6 23.8 25.2 25.3 %Gentamicin R* 7.7 9.9 1.2 7.7 9.4 8.7 9.7 9.7 %Gentamicin/Amikacin/Tobramycin R* 8.6 1.6 11. 9.3 11.8 12.2 12.6 12.8 %Carbapenem 1 R*........1 %MDR* 9. 11.4 12.1 1.4 11.7 13. 13.4 14.7 Number laboratories by year end 42 44 43 43 4 41 41 41 S. aureus 1412 1393 133 139 1251 195 16 194 Number Meticillin R (or MRSA) 592 536 439 355 35 263 242 222 %Meticillin R (or MRSA) 41.9 38.5 33.7 27.1 24.4 24. 22.8 2.3 Number laboratories by year end 42 44 42 43 4 41 41 41 E. faecium 265 33 46 397 392 364 392 49 %Ampicillin R* 93.9 93.1 95.1 92.9 95.6 95.9 92.9 93.2 %Vancomycin R (VREfm) 37.1 33.4 35.7 38.3 39.3 37.4 45.4 43.1 %HLG R* 44.3 35.2 28.1 39.1 39.6 36.8 39.3 41.4 %MDR* 25.6 22.7 16.2 26.7 24.9 21.1 2.3 19.6 Number laboratories by year end 42 44 42 43 4 41 41 41 E. faecalis 294 28 31 289 298 265 298 336 %Ampicillin R* 4.5 2.2.7 2.1 2..8 4. 2.7 %Vancomycin R (VREfa) 3.7 2.9 3.7.7.3 4.9 3. 2.1 %HLG R* 42.4 36.9 3.5 36.7 29.7 29.1 32.9 33.6 Number laboratories by year end 36 39 41 42 4 41 41 41 K. pneumoniae 217 244 31 323 326 312 345 326 %Ampicillin R* 97.7 99.2 99.7 99.7 99.1 1. 98.5 99.1 %3GC R* 1.2 9.9 11.4 11.2 1.5 8. 11.9 21.2 %ESBL producers* 8.6 3.7 7.7 8.2 5. 5.6 8.8 18.4 %Ciprofloxacin R* 15.3 18.1 12.8 13. 1.5 13.2 11.9 2.9 %Gentamicin R* 7.8 9.9 1.7 11.1 6.8 7.4 9.9 16.9 %Gentamicin/Amikacin/Tobramycin R* 9.2 11.1 1.7 11.1 7.1 8.3 9.6 17.5 %Carbapenem 1 R*..6... 1.6.3 1.2 %MDRKP 2 * 1.7 2.9 3.9 4.3 2.2 4.6 5.3 12.3 %MDR* 11.2 11.9 1.6 11.9 8. 8.4 9.9 19.1 Number laboratories by year end 42 44 42 43 4 41 41 41 S. pneumoniae 47 438 447 356 314 327 321 311 %Penicillin NS* 15.7 17.4 23.1 2.2 18.2 19.6 19.6 2.8 of which: %HLR 2.9 5.7 6. 5.6 4.8 6.1 4.7 2.3 %Int 12.5 11. 16.8 13.8 12.7 13.5 15. 18.3 %Erythromycin R* 16.1 16.4 16.7 17.3 15.7 18.9 16.9 17.9 %Penicillin NS/Erythromycin R 7.4 7.9 1.2 11.9 12.6 13.8 12.1 13.3 Number laboratories by year end 36 39 41 42 4 41 41 41 P. aeruginosa 128 177 199 248 222 184 219 27 %Piperacillin/tazobactam R* 9.4 12.6 9.7 8.9 1. 2.8 17.4 15.2 %Ceftazidime R* 1.6 11.8 8.7 11.8 9.2 8.2 15.2 1.7 %Imipenem/meropenem R* 11.8 12.2 9.3 1.2 8.3 12. 19.6 12.1 %Ciprofloxacin R* 18. 22.9 21.8 12.1 13.2 12.6 2.6 15. %Gentamicin R* 1.2 13.3 9. 7.7 8.7 6.5 11.9 11.6 %MDR* 9.5 12.4 11.1 6.4 6.5 4. 13. 9.4 Number laboratories by year end 41 Acinetobacter spp. 91 %Ciprofloxacin R* 3 %Gentamicin R* No data No data No data No data No data No data No data %Gentamicin/Amikacin/Tobramycin R* 1 %Carbapenem 1 R* 4 %MDR* Changes to previous reports are highlighted in RED Highest annual proportion reported in 213 R, Resistant; NS, Non Susceptible [includes isolates with intermediate (Int) and high level resistance (HLR)] Lowest annual proportion reported in 213 MRSA, Meticillin Resistant S. aureus ; VREfm, Vancomycin Resistant E. faecium; VREfa, Vancomycin Resistant E. faecalis HLG, High Level Gentamicin; 3GC, 3rd Generation Cephalosporin (includes cefotaxime, ceftriaxone, ceftazidime and cefpodoxime); ESBL, Extended Spectrum Beta Lactamase; MDR, Multi Drug Resistant * Not all isolates tested; ** 213 data provisional to the end of Q4 In 21, 3 laboratories stopped processing blood cultures, however coverage of acute hospitals remained at 1%; In Q3 211, one addi onal laboratory started repor ng 1 Carbapenems include imipenem, meropenem and ertapenem 2 MDRKP, MDR K. pneumoniae phenotype (ESBL producer plus non susceptibility to Ciprofloxacin and Gentamicin) OR carbapenemase producer (e.g. KPC, OXA 48) Page 2 of 18

Table 2. Summary of EARS Net data by pathogen and quarter, Q1 212 to Q4 213 (data correct as of 3/3/214) Pathogen E. coli Quarter 212Q1 212Q2 212Q3 212Q4 213Q1 213Q2 213Q3 213Q4 556 616 645 633 547 621 71 648 %Ampicillin R* 69.1 69.2 67.7 72.5 71.5 73.7 7. 68.8 %3GC R* 9.5 1.6 1.7 12.2 11.7 13.2 12.4 13.3 %ESBL producers* 8.5 7.5 9.7 9.5 9.5 1.8 9.3 12.1 %Ciprofloxacin R* 26.8 23.6 24.6 26. 24.3 27.8 23.4 25.8 %Gentamicin R* 9.7 7.8 9.9 11.3 7.5 11.6 1. 9.4 %Gentamicin/Amikacin/Tobramycin R* 12.4 1.6 12.4 14.9 1.6 14.3 13.1 12.8 %Carbapenem 1 R*......3.. %MDR* 13.4 12.7 13.4 14.2 11.9 16.5 14.7 15.3 S. aureus 276 269 23 285 258 283 32 251 Number Meticillin R (or MRSA) 72 56 46 68 47 65 66 44 %Meticillin R (or MRSA) 26.1 2.8 2. 23.9 18.2 23. 21.9 17.5 E. faecium 86 94 98 114 18 111 98 92 %Ampicillin R* 92 94 94 92 93 94 92 95 %Vancomycin R (VREfm) 51 47 44 46 44 37 42 45 %HLG R* 44 35 32 46 41 43 38 44 %MDR* 27 2 16 19 21 19 16 23 E. faecalis 84 57 81 76 77 86 98 75 %Ampicillin R* 5 4 7 3 6 3 %Vancomycin R (VREfa) 2 2 4 4 5 1 2 %HLG R* 36 35 27 34 32 35 34 34 K. pneumoniae 77 83 89 96 71 76 8 99 %Ampicillin R* 99 98 99 99 99 1 1 98 %3GC R* 12 11 13 12 15 21 24 23 %ESBL producers* 9 8 8 9 13 18 21 2 %Ciprofloxacin R* 18 13 1 7 18 21 26 18 %Gentamicin R* 1 8 11 8 17 12 23 16 %Gentamicin/Amikacin/Tobramycin R* 12 8 11 8 18 13 23 16 S. pneumoniae P. aeruginosa Acinetobacter spp. %Carbapenem 1 R* 1 1 1 2 %MDRKP 2 * 6 6 6 5 11 11 16 11 %MDR* 12 1 1 8 14 19 24 19 11 74 47 99 14 85 41 81 %Penicillin NS* 17 2 3 17 22 23 18 19 of which: %HLR 13 11 28 14 18 22 15 16 %Int 4 9 2 3 4 2 2 %Erythromycin R* 2 18 17 13 22 2 13 14 %Penicillin NS/Erythromycin R 12 14 13 1 16 11 1 14 59 45 58 57 35 37 66 69 %Piperacillin/tazobactam R* 12 11 19 26 14 19 18 1 %Ceftazidime R* 12 13 11 25 9 14 15 6 %Imipenem/meropenem R* 19 18 18 24 17 17 9 1 %Ciprofloxacin R* 25 22 14 21 3 22 2 13 %Gentamicin R* 14 11 11 12 3 16 15 1 %MDR* 14 13 7 18 6 17 12 4 14 15 28 34 %Ciprofloxacin R* 7 7 4 %Gentamicin R* No data No data No data No data %Gentamicin/Amikacin/Tobramycin R* 3 %Carbapenem 1 R* 8 8 3 %MDR* MRSA, Meticillin Resistant S. aureus ; VREfm, Vancomycin Resistant E. faecium; VREfa, Vancomycin Resistant E. faecalis R, Resistant; NS, Non Susceptible [includes isolates with intermediate (Int) and high level resistance (HLR)] HLG, High Level Gentamicin; 3GC, 3rd Generation Cephalosporin (includes cefotaxime, ceftriaxone, ceftazidime and cefpodoxime); ESBL, Extended Spectrum Beta Lactamase; MDR, Multi Drug Resistant * Not all isolates tested 1 Carbapenems include imipenem, meropenem and ertapenem 2 MDRKP, MDR K. pneumoniae phenotype (ESBL producer plus non susceptibility to Ciprofloxacin and Gentamicin) OR carbapenemase producer (e.g. KPC, OXA 48) Page 3 of 18

Table 3. Summary of EARS Net data by pathogen and HSE Area, 213 (data correct as of 3/3/214) Pathogen E. coli S. aureus E. faecium E. faecalis K. pneumoniae S. pneumoniae P. aeruginosa Acinetobacter spp. HSE Area Dublin/Mid Leinster Dublin/North East South West 694 559 532 565 2526 %ESBL producers* 8.1 8. 8.9 17.4 1.4 %MDR* 13.9 12.2 11.3 21.4 14.7 341 213 216 238 194 Number Meticillin R (or MRSA) 59 3 6 64 222 %Meticillin R (or MRSA) 17.3 14.1 27.8 26.9 2.3 133 8 71 98 49 %Vancomycin R (VREfm) 52.6 36.3 38. 44.9 43.1 %MDR* 26.9 17.3 21.1 13.4 19.6 82 79 68 74 336 %Vancomycin R (VREfa) 4 1 2 3 2.1 17 63 57 61 326 %ESBL producers* 24 13 11 23 18.4 %Carbapenem 1 R* 4 1.2 %MDRKP 2 * 2 6 5 16 12.3 %MDR* 27 11 14 23 19.1 76 73 74 66 311 %Penicillin NS* 21 16 2 21 2.8 %Penicillin NS/Erythromycin R 13 13 7 18 13.3 Changes to previous reports are highlighted in RED 46 49 44 46 27 %MDR* 7 1 5 13 9.4 26 8 21 2 91 %MDR*. MRSA, Meticillin Resistant S. aureus; VREfm, Vancomycin Resistant E. faecium ; VREfa, Vancomycin Resistant E. faecalis R, Resistant; NS, Non Susceptible (includes isolates with intermediate and high level resistance) ESBL, Extended Spectrum Beta Lactamase; MDR, Multi Drug Resistant * Not all isolates tested 1 Carbapenems include imipenem, meropenem and ertapenem 2 MDRKP, MDR K. pneumoniae phenotype (ESBL producer plus non susceptibility to Ciprofloxacin and Gentamicin) OR carbapenemase producer (e.g. KPC, OXA 48) Page 4 of 18 National

Invasive E. coli infections Number Invasive E. coli cases: 2,526 Number ESBL-positive E. coli cases: 262 (of 2,51 tested) % ESBL-positive E. coli: 1.4% Number MDR E. coli cases: 37 (of 2,52 tested) % MDR E. coli: 14.7% Commentary: Number and % ESBL-positive and MDR E. coli are the highest since surveillance began in 22 ESBL-positive and MDR E. coli have been increasing since 24 E. coli data, 213 (Q1 4) 2,526 isolates (2,521 from blood and 5 from CSF) 32 (12.7%) of2,524 isolates were resistant to 3GCs, of which 254 were ESBL positive and 64 were ESBL negative; 638 (25.3%) of 2,522 were ciprofloxacin resistant; and 245 (9.7%) of 2,524 were gentamicin resistant [323 (12.8%) of 2,526 were aminoglycoside resistant (i.e. resistant to gentamicin, tobramycin or amikacin)] 262 (1.4%) of 2,51 isolates were ESBL positive 2 (.1%) of 2,52 isolates were resistant to carbapenems (imipenem or meropenem), neither of which was carbapenemase producer. It is probable that the resistance mechanism in these was due to a combination of ESBL production (both were positive) and porin loss 371 (14.7%) of 2,25 isolates from 48 hospitals/institutions were MDR, i.e. resistant to 3 or more of the required antibiotic classes [ampicillin, 3GCs (e.g. cefotaxime, ceftazidime), fluoroquinolones (e.g. ciprofloxacin) and aminoglycosides (as above)]: o 149 with resistance to ampicillin, 3GCs, ciprofloxacin and aminoglycosides (136 ESBL positive, 17 negative) o 15 with resistance to ampicillin, 3GCs and ciprofloxacin (87 ESBL positive, 17 negative) o 7 with resistance to ampicillin, 3GCs and aminoglycosides (5 ESBL positive, 2 negative) o 11 with resistance to ampicillin, ciprofloxacin and aminoglycosides (one ESBL positive, 18 negative) 3 25 2 15 1 5 24 25 26 27 28 29 21 211 212 213* Total E. coli %3GC R %ESBL+ve 16% 14% 12% 1% 8% 6% 4% 2% % %3GC R/ESBL+ve Figure 1. Trends for ESBL producing E. coli total numbers of ESBL producers and percentage positivity (with percentage 3GC resistance for comparison) with 9CIs * Data for 213 are provisional to the end of Q4 Figure 2. Distribution of 3 rd -generation cephalosporin-resistant E. coli in EARS-Net countries in 212 Map obtained from ECDC on 6/3/214: http://www.ecdc.europa.eu/en/healthtopics/antimicrobial_resistance/data base/pages/map reports.aspx Page 5 of 18

E. coli trends in resistance Resistance to 3GCs increased from 2.6% in 24 to 12.7% in 213 (to the end of Q4), while the proportion of ESBL producers increased from 1.1% to 1.4% over the same period. Both are provisionally the highest annual proportions reported to date (Figure 1) Between 29 and 213 (to the end of Q4): o resistance to ciprofloxacin increased from 22.3% to 25.3% while resistance to aminoglycosides increased from 9.3% to 12.8%, both of which are the highest annual proportions reported to date (Figure 3) o MDR isolates increased from 1.4% to 14.7%, the highest annual proportion reported to date (Figure 4) 3 3% 3 18% 25 25 16% 14% 2 15 1 5 2% 1% %Resistance 2 15 1 5 12% 1% 8% 6% 4% 2% %MDR ECO 24 25 26 27 28 29 21 211 212 213* Total E. coli %3GC R %FQREC %GEN R %GEN/TOB/AMK R Figure 3. Trends for E. coli total numbers of E. coli and percentage resistance to 3GCs, ciprofloxacin/ofloxacin (CIP/OFX), gentamicin (GEN) and gentamicin/tobramycin /amikacin (GEN/TOB/AMK) with 9CIs * Data for 213 are provisional to the end of Q4 % 24 25 26 27 28 29 21 211 212 213* Total E. coli tested for MDR MDR ECO %MDR Figure 4. Trends for Multi Drug Resistant (MDR) E. coli total numbers of MDR E. coli and percentage MDR with 9CIs * Data for 213 are provisional to the end of Q4 % Page 6 of 18

S. aureus bloodstream infections Number S. aureus BSI cases: 1,94 Number MRSA cases: 222 % MRSA: 2.3% Commentary: Number and % MRSA are the lowest since surveillance began in 1999 MRSA has been decreasing since 26 S. aureus data, 213 (Q1 4) 1,94 isolates, of which 222 (2.3%) were MRSA 91 (43.8%) of 28 MRSA isolates were fusidic acid resistant compared with 12 (15.%) of 799 MSSA isolates Among MRSA, 3 isolates (1.) were resistant to rifampicin (n=21). No resistance was detected to linezolid (n=22) No isolates with reduced susceptibility to glycopeptides were detected by the National MRSA Reference Laboratory S. aureus trends in resistance The annual trends indicate the proportion of MRSA in Ireland decreased from 41.9% in 26 to 22.8% in 212 and 2.3% in 213 (to the end of Q4), which is provisionally the lowest annual proportion since surveillance began in 1999 (Figure 5) Between 26 (when the number of MRSA bloodstream infections peaked) and 213, the overall MRSA numbers decreased by 63% For the latest data on S. aureus/mrsa by acute hospital in Ireland, see: http://www.hpsc.ie/hpsc/a Z/MicrobiologyAntimicrobialResistance/EuropeanAntimicrobialResistanceSurveillanceSystemEARSS/ReferenceandEdu cationalresourcematerial/saureusmrsa/latestsaureusmrsadata/ 16 14 12 1 8 6 4 2 24 25 26 27 28 29 21 211 212 213* Total S. aureus MRSA %MRSA 4 4% 3 3% 2% 1% % %MRSA Figure 5. Trends for S. aureus total numbers of S. aureus/mrsa and percentage MRSA with 9CIs * Data for 213 are provisional to the end of Q4 Figure 6. Distribution of MRSA in EARS-Net countries in 212 Map obtained from ECDC on 6/3/214: http://www.ecdc.europa.eu/en/healthtopics/antimicrobial_resistance/ database/pages/map_reports.aspx Page 7 of 18

E. faecium bloodstream infections Number E. faecium BSI cases: 49 Number vancomycin-resistant E. faecium, or VREfm, cases: 176 (of 48 tested) % VREfm: 43.1% Commentary: Ireland has the highest proportion of E. faecium that are VREfm in Europe and was the only country reporting a proportion in excess of in 212 (Figure 8) E. faecium data, 213 (Q1 4) 49 isolates 281 (68.7%) of 49 isolates were from the 9 tertiary/teaching hospitals 176 (43.1%) of 48 were resistant to vancomycin (i.e. vancomycin resistant E. faecium or VREfm) and 165 (41.4%) of 399 isolates were resistant to high level gentamicin (HLG) 78 (19.6%) of 398 isolates from 8 hospitals were MDR, defined as resistant to ampicillin, HLG and vancomycin E. faecium trends in resistance The annual trends indicate that the proportion of VREfm increased from 33.4% in 27 to 45.4% in 212, which is the highest annual proportion since surveillance began in 22 (Figure 7). In 213 (to the end of Q4), the proportion of VRE decreased to 43.1% Ireland has the highest proportion of VREfm in Europe. In 212, it was the only country to report a proportion in excess of (Figure 9) The proportion of MDR isolates decreased from 26.7% (the highest proportion reported to date) in 29 to 19.6% in 213 (to the end of Q4) (Figure 1) 45 4 35 3 25 2 15 1 5 24 25 26 27 28 29 21 211 212 213* Total E. faecium %VREfm %HLGR Efm 7% 6% 4% 3% 2% 1% % %Resistance Figure 7. Trends for E. faecium total numbers of E. faecium and percentage resistance to high level gentamicin (HLGR Efm) and vancomycin (VREfm) with 9CIs * Data for 213 are provisional to the end of Q4 Figure 8. Distribution of vancomycin-resistant E. faecium (VREfm) in EARS-Net countries in 212 Map obtained from ECDC on 6/3/214: http://www.ecdc.europa.eu/en/healthtopics/antimicrobial_resistance/ database/pages/map_reports.aspx Page 8 of 18

45 4 35 3 25 2 15 1 5 3 3% 2% 1% %MDR Figure 9. Distribution of high-level gentamicin-resistant E. faecium (HLGR-Efm) in EARS-Net countries in 212 Map obtained from ECDC on 6/3/214: http://www.ecdc.europa.eu/en/healthtopics/antimicrobial_resistance/ database/pages/map_reports.aspx 24 25 26 27 28 29 21 211 212 213* Total E. faecium tested for MDR MDR EFM %MDR EFM Figure 1. Trends for Multi Drug Resistant (MDR) E. faecium total numbers of MDR E. faecium and percentage MDR with 9CIs * Data for 213 are provisional to the end of Q4 % Page 9 of 18

E. faecalis bloodstream infections Number E. faecalis BSI cases: 336 Number vancomycin-resistant E. faecalis, or VREfa, cases: % VREfa: 7 (of 334 tested) 2.1% Commentary: Ireland had the highest proportion (3.%) of E. faecalis that are VREfa in Europe in 212 E. faecalis data, 213 (Q1 4) 336 isolates 7 (2.1%) of 334 were resistant to vancomycin (i.e. vancomycin resistant E. faecalis or VREfa), 17 (33.) of 319 isolates were resistant to HLG and 9 of 98 were resistant to ampicillin (Note: resistance to ampicillin among E. faecalis is an unusual finding) E. faecalis trends in resistance The numbers and proportions of VREfa isolates have fluctuated over the years (Figure 11). In 211, 4.9% (n=13) of isolates were VREfa, which was the highest proportion since surveillance began in 22 Although the proportion of VREfa is low, Ireland still has one of the highest proportions among countries reporting to EARS Net. In 212, Ireland had the highest proportion (3.%) in Europe (Figure 12) 4 35 3 25 2 15 1 5 24 25 26 27 28 29 21 211 212 213* Total E. faecalis tested for VAN VREfa %VREfa 12% 1% 8% 6% 4% 2% % 2% 4% 6% %VREfm Figure 11. Trends for vancomycin resistant E. faecalis (VREfa) total numbers of VREfa and percentage VREfa with 9CIs * Data for 213 are provisional to the end of Q4 Figure 12. Distribution of vancomycin-resistant E. faecalis (VREfa) in EARS-Net countries in 212 Map obtained from ECDC on 6/3/214: http://www.ecdc.europa.eu/en/healthtopics/antimicrobial_resistance/ database/pages/map_reports.aspx Page 1 of 18

Invasive K. pneumoniae infections Number Invasive K. pneumoniae cases: 326 Number ESBL-positive K. pneumoniae cases: 6 % ESBL-positive K. pneumoniae: 18.4% Commentary: Number and % ESBL-positive are the highest since surveillance began in 26 ESBL-positive K. pneumoniae have increased significantly over the past 3 years K. pneumoniae data, 213 (Q1 4) 326 isolates (323 from blood and 3 from CSF) 69 (21.2%) of 325 isolates were resistant to 3GCs, 6 of which were ESBL positive and 9 were ESBL negative; 68 (2.9%) of 325 were ciprofloxacin resistant; and 55 (16.9%) of 325 were gentamicin resistant [57 (17.) of 326 were aminoglycoside resistant (i.e. resistant to gentamicin, tobramycin or amikacin)] 3 (.9%) of 325 isolates were susceptible to ampicillin (Note: ampicillin susceptibility among K. pneumoniae is unusual) 62 (19.1%) of 325 isolates from 17 hospitals were MDR (defined as resistance to 2 or more of the key antibiotics required by the EARS Net protocol): o 42 with resistance to ampicillin, 3GCs, ciprofloxacin and aminoglycosides (38 ESBL positive, 4 negative) o 7 with resistance to ampicillin, 3GCs and ciprofloxacin (all ESBL positive) o 6 with resistance to ampicillin, 3GCs and aminoglycosides (5 ESBL positive, one negative) o 6 with resistance to ampicillin, ciprofloxacin and aminoglycosides (all ESBL negative) Of 326 isolates, 6 (18.4%) were found to produce ESBLs 4 carbapenem resistant enterobacteriaceae (CRE) isolates were reported from 326 isolates, 2 of which were confirmed carbapenemase producers (both OXA 48) and also resistant to ampicillin, 3GCs, ciprofloxacin and aminoglycosides (ESBL negative) (i.e. MDR). No carbapenemase was detected in the other 2 isolates and it is probable that the resistance mechanism in these was due to a combination of ESBL production (both were positive) and porin loss K. pneumoniae trends in resistance Between 21 and 213 (to the end of Q4), resistance to ciprofloxacin [2.9% (21, 1.)], gentamicin [16.9% (21, 6.8%)] and aminoglycosides [17. (21, 7.1%)] and ESBL producers [18.4% (21, 5.%)] (Figures 13 and 15) increased. Between 211 and 213 (to the end of Q4), resistance to 3GCs [21.2% (211, 8.%)] also increased (Figure 13). All of these are provisionally the highest annual proportions reported to date In 212, many Eastern and Southern European countries reported proportions in excess of to EARS Net (Figure 14). Ireland had one of the lowest proportions in 212, but the provisional data for 213 indicate that proportion of 3GC resistance has almost doubled here over the past year Between 21 and 213 (to the end of Q4), the proportion of MDR increased from 8.% to 19.1%, which is provisionally the highest annual proportions reported to date (Figure 16) In 213, 2 carbapenemase producing CRE (CPE) isolates (both OXA 48) were reported. In 211, there were 4 CPE isolates of K. pneumoniae, which were the first reports of invasive CRE due to carbapenemases in Ireland (Figure 17) Carbapenem resistance is already a major problem in Greece and Italy, with proportions of 62% and 31%, respectively, in 212 (Figure 18) Among isolates that belonged to a particular MDR profile, or MDRKP phenotype (i.e. were simultaneously NON SUSCEPTIBLE to ciprofloxacin and gentamicin AND ESBL producers), 2 major clonal groups have been identified (Source: Antibiotic Resistance and Microbial Ecology (ARME) Laboratory, National University Ireland, Galway). In 213, 38 isolates (of 325, or 1.7%) reported to EARS Net were identified with this phenotype compared with 18 (of 342, or 5.3%) in 212 and 1 (of 34, or 3.3%) in 211 (Figure 19) Page 11 of 18

4 35 3 25 2 15 1 5 36 39 41 42 4 41 41 41 26 27 28 29 21 211 212 213* Total KPN %3GC R %ESBL+ve 3% 2% 1% % %3GC R/ESBL+ve Figure 13. Trends for ESBL producing K. pneumoniae total numbers of ESBL producers and percentage positivity (with percentage 3GC resistance for comparison) with 9CIs * Data for 213 are provisional to the end of Q4; the numbers of participating laboratories by year end are indicated above the bars Figure 14. Distribution of 3GC resistant K. pneumoniae in EARS-Net countries in 212 Map obtained from ECDC on 6/3/214: http://www.ecdc.europa.eu/en/healthtopics/antimicrobial_resistance/dat abase/pages/map_reports.aspx 4 36 39 41 42 4 41 41 41 3% 4 36 39 41 42 4 41 41 41 35 3 25 2 15 1 5 2% 1% %Resistance 35 3 25 2 15 1 5 2% 1% %MDR 26 27 28 29 21 211 212 213* Total KPN %3GC R %CIP/OFX R %GEN/TOB/AMK R %GEN R Figure 15. Trends for K. pneumoniae total numbers of K. pneumoniae and percentage resistance to 3GCs, ciprofloxacin/ofloxacin (CIP/OFX), gentamicin (GEN) and gentamicin/tobramycin/amikacin (GEN/TOB/AMK) with 9CIs * Data for 213 are provisional to the end of Q4; the numbers of participating laboratories by year end are indicated above the bars % 26 27 28 29 21 211 212 213* Total KPN tested for MDR MDR KPN %MDR Figure 16. Trends for Multi Drug Resistant K. pneumoniae total numbers of MDR K. pneumoniae and percentage MDR with 9CIs * Data for 213 are provisional to the end of Q4; the numbers of participating laboratories by year end are indicated above the bars % 4 35 3 25 2 15 1 5 36 39 41 42 4 41 41 41 4% 3% 2% 1% %CBP R 26 27 28 29 21 211 212 213* Total K. pneumoniae tested for CBP CBP R KPN %CBP R Figure 17. Trends for carbapenem (CBP) resistant K. pneumoniae total numbers and percentage resistance to CBP with 9CIs * Data for 213 are provisional to the end of Q4; the numbers of participating laboratories by year end are indicated above the bars Carbapenems include imipenem, meropenem and ertapenem % Page 12 of 18 Figure 18. Distribution of carbapenem resistant K. pneumoniae in EARS-Net countries in 212 Map obtained from ECDC on 6/3/214: http://www.ecdc.europa.eu/en/healthtopics/antimicrobial_resistance/dat abase/pages/map_reports.aspx

Number of cases 4 35 3 25 2 15 1 5 26 27 28 29 21 211 212 213* 14% 12% 1% 8% 6% 4% 2% % % of all cases No. MDRKP phenotype %MDRKP phenotype Figure 19. Trends for K. pneumoniae isolates with the MDRKP phenotype (simultaneously NON SUSCEPTIBLE to ciprofloxacin and gentamicin AND ESBL producers) numbers and percentage with MDRKP phenotype with 9CIs * Data for 213 are provisional to the end of Q4 Page 13 of 18

Invasive S. pneumoniae infections Number invasive S. pneumoniae cases: 311 Number penicillin-non-susceptible S. pneumoniae, or PNSP: % PNSP: 64 (of 38 tested) 2.8% Number S. pneumoniae cases with non-susceptibility to both penicillin and erythromycin ( Pen/Ery-NS): 39 (of 293 tested) % Pen/Ery-NS S. pneumoniae: 13.3% Commentary: The % PNSP in 213 was the 2 nd highest proportion reported since surveillance began in 1999 Ireland had one of the highest proportions of PNSP in Europe in 212 S. pneumoniae data, 213 (Q1 4) 311 isolates (34 from blood and 7 from CSF) CLSI guidelines distinguish between non meningitis [Susceptible (S) 2 mg/l, Intermediate (I) 4 mg/l, Resistant (R) 8 mg/l] and meningitis breakpoints (S.6 mg/l, R.12 mg/l) for iv/parenteral penicillin and recommend that blood isolates should be reported using both sets of breakpoints. EUCAST guidelines distinguish between non meningitis [Susceptible (S).6 mg/l, Intermediate (I).12 2 mg/l, Resistant (R) 4 mg/l] and meningitis breakpoints (S.6 mg/l, R.12 mg/l) for benzylpenicillin EARSS previously recommended using the old CLSI breakpoints (S.6 mg/l, I.12 1. mg/l, R 2 mg/l), corresponding to the new oral breakpoints, for surveillance purposes, to avoid confusion with interpretation of historic data and until a consensus approach could be agreed. The EUCAST non meningitis breakpoints (S.6 mg/l, I.12 2 mg/l, R 4 mg/l) are very similar to these, hence to facilitate a more meaningful analysis of the data, the oral breakpoints are used for the 14 laboratories still following CLSI (accounting for 33% of S. pneumoniae isolates and 33% of all EARS Net isolates reported in Q4 213) and the meningitis breakpoints for the 27 laboratories following EUCAST (accounting for 67% of S. pneumoniae, as well as for 67% of all EARS Net isolates) ***Penicillin and cefotaxime/ceftriaxone MICs should be submitted on all pneumococcal isolates*** 64 (2.8%) of 38 isolates were PNSP (defined as having a penicillin MIC of.12 mg/l) (Note: 3 additional isolates were reported as penicillin susceptible but with no MICs) and 54 (17.9%) of 32 isolates were resistant to erythromycin Penicillin and cefotaxime/ceftriaxone MICs were available for 64 and 62 PNSP isolates, respectively 7 isolates were high level resistant and 57 were intermediately resistant to penicillin. Ten PNSP isolates (3 high level resistant and 7 intermediately resistant) were non susceptible to cefotaxime Erythromycin resistance was reported in 39 PNSP (6 high level resistant and 33 intermediately resistant) isolates and 12 PSSP isolates For 213, 21 (64.6%) of 311 pneumococcal isolates reported were referred to RCSI/Temple St for capsular serotyping (using a combination of multiplex PCR and conventional serological methods) (Note: no serotyping data were available for Q4 213 isolates at the time of this report). Serotype coverage among the target population for each vaccine, <2 years for PCV13 and 65 years for PPV23, was 3% (3 of 1 isolates) and 68% (7 of 13 isolates), respectively. The most common serotypes identified were 7F (n=34), 19A (n=23), 3 (n=13) and 22F (n=12) representing 41% of all isolates typed S. pneumoniae trends in resistance The annual trends indicate that the proportion of PNSP increased from 18.2% in 29 to 2.8% in 213 (to the end of Q4), which is provisionally the 2 nd highest annual proportion since surveillance began (Figure 2) In 212, Ireland had the 4 th highest proportion of PNSP of countries in Europe reporting over 5 isolates (Figure 21) In 213 (to the end of Q4), the proportion of S. pneumoniae with resistance to erythromycin (17.9%) is provisionally the 2 nd highest annual proportion reported to date (Figure 22) Between 25 and 211, co resistance to penicillin and erythromycin amongst S. pneumoniae isolates increased significantly from 3.2% to 13.8%, which was the highest proportion reported to date (Figure 23). In 213, the proportion remains at a high level (13.2%) Page 14 of 18

5 45 4 35 3 25 2 15 1 5 3% 2% 1% %PNSP % 24 25 26 27 28 29 21 211 212 213* Total S.pneumoniae PNSP %I %HLR %PNSP Figure 2. Trends for S. pneumoniae total numbers of S. pneumoniae/penicillin Non Susceptible S. pneumoniae (PNSP) and percentage PNSP [penicillin intermediate (Pen I) and high level resistant (Pen HLR)] with 9CIs * Data for 213 are provisional to the end of Q4 Figure 21. Distribution of penicillin non-susceptible S. pneumoniae (PNSP) in EARS-Net countries in 212 Map obtained from ECDC on 6/3/214: http://www.ecdc.europa.eu/en/healthtopics/antimicrobial_resistance /database/pages/map_reports.aspx 5 5 2% 45 45 18% 4 2% 4 16% 35 3 25 2 15 1% %ENSP 35 3 25 2 15 14% 12% 1% 8% 6% %PEN/ERY R 1 1 4% 5 5 2% % % 24 25 26 27 28 29 21 211 212 213* 24 25 26 27 28 29 21 211 212 213* Total S.pneumoniae ENSP %ENSP Total S.pneumoniae Pen/Ery NS %Pen/Ery NS Figure 22. Trends for S. pneumoniae total numbers of S. pneumoniae/erythromycin Non Susceptible S. pneumoniae (ENSP) and percentage ENSP with 9CIs * Data for 213 are provisional to the end of Q4 Figure 23. Trends for S. pneumoniae total numbers of S. pneumoniae/co resistant to penicillin and erythromycin (Pen/Ery NS) and percentage Pen/Ery NS with 9CIs * Data for 213 are provisional to the end of Q4 Page 15 of 18

Invasive P. aeruginosa infections Number Invasive P. aeruginosa cases: 27 Number MDR cases: 262 (of 2,51 tested) % MDR: 9.4% Commentary: Resistance to all 5 key antibiotic classes decreased in 213 The highest number and proportion of isolates with resistance to piperacillintazobactam, ceftazidime and imipenem/meropenem were reported in 212 P. aeruginosa data, 213 (Q1 4) 27 isolates (26 from blood and one from CSF) 31 (15.2%) of 24 isolates were resistant to piperacillin tazobactam; 22 (1.7%) of 26 were resistant to ceftazidime; 25 (12.1%) of 26 were resistant to imipenem or meropenem; 32 (15.) of 27 was resistant to ciprofloxacin; and 24 (11.6%) of 27 were resistant to gentamicin [no additional isolates were resistant to the other aminoglycosides (amikacin or tobramycin)] 19 (1.4%) of 23 isolates from 13 hospitals were MDR including: o 3 with resistance to all 5 key antibiotics classes o 1 with resistance to 4 of the 5 key antibiotics classes o 6 with resistance to 3 of the 5 key antibiotics classes P. aeruginosa trends in resistance In 213 (to the end of Q4), the proportion of isolates with resistance to all 5 key antibiotic classes decreased compared to 212 (Figures 24 and 25) In 212, resistance to piperacillin tazobactam (17.4%), ceftazidime (15.2%) and imipenem/meropenem (19.6%) were the highest annual proportions reported for these to date (Figure 24) The proportion of MDR (13.%) in 212 was the highest annual proportion reported to date (Figure 26) 3 36 39 41 42 4 41 41 41 3% 3 36 39 41 42 4 41 41 41 3 25 25 3% 2 15 1 2% 1% %Resistance 2 15 1 2% 1% %Resistance 5 5 % 26 27 28 29 21 211 212 213* Total PAE %PIP/TZP R %CAZ R %IPM/MEM R 26 27 28 29 21 211 212 213* Total PAE %GEN R %CIP/OFX R % Figure 24. Trends for P. aeruginosa total numbers of P. aeruginosa and percentage resistance to piperacillintazobactam (PIP/TZP), ceftazidime (CAZ) and imipenem/ meropenem (IPM/MEM) with 9CIs * Data for 213 are provisional to the end of Q4; the numbers of participating laboratories by year end are indicated above the bars Figure 25. Trends for P. aeruginosa total numbers of P. aeruginosa and percentage resistance to ciprofloxacin/ ofloxacin (CIP/OFX) and gentamicin (GEN) with 9CIs *Data for 213 are provisional to the end of Q4; the numbers of participating laboratories by year end are indicated above the bars Page 16 of 18

25 2 15 1 5 36 39 41 42 4 41 41 41 26 27 28 29 21 211 212 213* Total P. aeruginosa tested for MDR MDR %MDR Figure 26. Trends for P. aeruginosa total numbers of P. aeruginosa and percentage resistance to piperacillintazobactam (PIP/TZP), ceftazidime (CAZ) and imipenem/ meropenem (IPM/MEM) with 9CIs * Data for 213 are provisional to the end of Q4; the numbers of participating laboratories by year end are indicated above the bars 2% 18% 16% 14% 12% 1% 8% 6% 4% 2% % %MDR Figure 27. Distribution of carbapenem resistant P. aeruginosa in EARS-Net countries in 212 Map obtained from ECDC on 6/3/214: http://www.ecdc.europa.eu/en/healthtopics/antimicrobial_resistance /database/pages/map_reports.aspx Page 17 of 18

Invasive Acinetobacter spp. infections Number Invasive Acinetobacter spp. cases: 91 Commentary: Low levels of resistance in Ireland but interpret with caution as low numbers of cases Acinetobacter spp data, 213 (Q1 4) 91 isolates (low numbers: interpret with caution) from 28 hospitals/institutions in all HSE Areas 49 (53%) of 91 isolates were from the 5 tertiary/teaching hospitals 3 (3%) of 89 were resistant to ciprofloxacin (fluoroquinolones), one (1%) of 89 isolates were resistant to aminoglycosides and 3 (4%) of 86 were resistant to carbapenems No isolates were MDR Page 18 of 18