EARS-Net data on Antimicrobial Resistance in Ireland, Q

EARS-Net data on antimicrobial resistance in Ireland Quarter 3 2016 6th December 2016

EARS-Net data on Antimicrobial Resistance in Ireland, Q1-3 2016
KEY POINTS, 2016 (General) Escherichia coli The numbers of invasive E. coli infections have increased since 2004 The proportion of ESBL-positive E. coli increased in 2016* Staphylococcus aureus/ MRSA The number and proportion of MRSA bloodstream infections have decreased since 2006; however, in contrast to this, the rate of MSSA BSIs is increasing 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): the proportion of MDRKP among invasive K. pneumoniae infections decreased in 2016* Carbapenem-resistance, particularly as a result of carbapenemase production, among K. pneumoniae decreased in 2016*, but in recent years the trend has been increasing Enterococcus faecium/ VREfm (vancomycin-resistant E. faecium) Ireland has had the highest proportion of VREfm in Europe since 2008 Pseudomonas aeruginosa The proportion of multi-drug resistant P. aeruginosa has increased in 2016* * 2016 data provisional to the end of Q3 only EARS-Net data on Antimicrobial Resistance in Ireland, Q

KEY POINTS, 2016* (1) Escherichia coli The numbers of invasive E. coli infections have increased since 2004 (note: the decrease in 2015 was due to incomplete reporting by 3 laboratories) The proportion of patients with invasive infections caused by E. coli producing extended-spectrum beta-lactamases (ESBLs) increased to 11.1%, the highest proportion to date The proportion of invasive infections caused by multi-drug resistant (MDR) E. coli (displaying resistance to three or more antimicrobial classes) decreased to 14.0% Staphylococcus aureus/ MRSA The proportion of S. aureus bloodstream infections (BSIs) that were meticillin-resistant (MRSA) decreased to14.7%, the lowest proportion to date In contrast to this, the rate of meticillin-susceptible S. aureus (MSSA) BSIs is increasing Klebsiella pneumoniae The proportion of patients with invasive infections caused by multi-drug resistant K. pneumoniae (MDRKP) decreased to 7.4% The proportion of patients with invasive infections caused by carbapenem-resistant K. pneumoniae isolates decreased to 1.2%, but in recent years the overall trend has been increasing *2016 data provisional to the end of Q3 only EARS-Net data on Antimicrobial Resistance in Ireland, Q

KEY POINTS, 2016* (2) Enterococcus faecium/ VREfm (vancomycin-resistant E. faecium) Since 2012, the proportion of E. faecium BSI that are vancomycin-resistant (i.e. VREfm) has been over 40% Ireland has had the highest proportion of VREfm in Europe since 2008 Pseudomonas aeruginosa The proportion of patients with invasive infections caused by multi-drug resistant P. aeruginosa increased to 14.9%, the highest proportion to date *2016 data provisional to the end of Q3 only EARS-Net data on Antimicrobial Resistance in Ireland, Q

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, Q

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 data on Antimicrobial Resistance in Ireland, Q

Data Management Nationally 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 WHONET files* LIMS files*, that can be translated to WHONET via BacLink software Excel template* Isolate Record Forms *all electronic files should be encrypted before being sent to HPSC by EARS-Net data on Antimicrobial Resistance in Ireland, Q

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 and 2016, a number of laboratories suspended their participation due to resource issues: Midland Regional Hospital Portlaoise between Q2 and Q and from Q onwards Midland Regional Hospital Tullamore between Q2 and Q3 2015 Letterkenny General Hospital between Q3 and Q4 2015 In addition, data submission from one laboratory in Q was delayed The overall population coverage by EARS-Net was estimated to be ~97% in 2015 and ~99% for Q Note: estimated population coverage by EARS-Net in other EU/EEA countries varies considerably from <20% to 100% EARS-Net data on Antimicrobial Resistance in Ireland, Q

Data Management EUCAST vs CLSI (situation as of Q1 2016) 34 labs have now adopted EUCAST guidelines = 93% of all isolates 5 labs still using CLSI Data collection (in Q1 2016) WHONET – 22 labs – representing 86% of data LIMS file – 2 labs – 5% of data Excel – 3 labs – 4% of data Paper forms – 11 labs – 5% of data No data – 2 labs EARS-Net data on Antimicrobial Resistance in Ireland, Q

Escherichia coli EARS-Net data on Antimicrobial Resistance in Ireland, Q

Escherichia coli invasive infections
Extrapolated: 2796 * 2016 data are provisional to the end of Q3 only (note: data missing from 2 laboratories for Q3); ‡ 2015 missing data from 3 laboratories for 2 quarters each: extrapolated figures in 2015 account for missing data using data for the same time period in the previous year AMP, Ampicillin; 3GC, 3rd-generation cephalosporins; FQ, fluoroquinolones; GEN, gentamicin; AG, aminoglycosides; MDR, multi-drug resistance Key messages: The numbers of invasive E. coli infections have increased since 2004 (note: the decrease in 2015 was due to incomplete reporting by 3 laboratories) ESBL-positive E. coli increased to 11.1% in 2016*, which is the highest proportion (%) to date *2016 data provisional to the end of Q3 only EARS-Net data on Antimicrobial Resistance in Ireland, Q

Trends in E. coli invasive infections showing percentage resistance to fluoroquinolones, aminoglycosides and 3rd-generation cephalosporins * 2016 data are provisional to the end of Q3 only (note: data missing from 2 laboratories for Q3); ‡ 2015 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, 3rd-generation cephalosporins (e.g. cefotaxime, ceftazidime) EARS-Net data on Antimicrobial Resistance in Ireland, Q

Trends in E. coli invasive infections showing percentage 3GC-resistance and ESBL-positivity * 2016 data are provisional to the end of Q3 only (note: data missing from 2 laboratories for Q3); ‡ 2015 missing data from 3 laboratories for 2 quarters each 3GC, 3rd-generation cephalosporins (e.g. cefotaxime, ceftazidime); ESBL, extended-spectrum beta-lactamase EARS-Net data on Antimicrobial Resistance in Ireland, Q

Distribution of 3rd-generation cephalosporin resistant E. coli in EARS-Net countries in 2014 IE rank (2014; 11.6%): 13th of 29 countries Median = 11.3% Trends 12 countries 1 country Map downloaded from ECDC’s TESSy database on 21/10/2015: EARS-Net data on Antimicrobial Resistance in Ireland, Q

Trends in E. coli invasive infections with percentage multi-drug resistance * 2016 data are provisional to the end of Q3 only (note: data missing from 2 laboratories for Q3); ‡ 2015 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, Q

Carbapenase-producing carbapenem-resistant enterobacteriaceae (CRE)
Extrapolated: 2796 *2016 data are provisional to the end of Q3 only (note: data missing from 2 laboratories for Q3); ‡ 2015 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; CPE, carbapenemase-producing enterobacteriaceae Key messages: 4 confirmed carbapenemase-producing E. coli isolates from invasive infections reported to date: three NDM (one each in 2014, 2015 and 2016) and one OXA-48 (in 2015) EARS-Net data on Antimicrobial Resistance in Ireland, Q

Staphylococcus aureus
EARS-Net data on Antimicrobial Resistance in Ireland, Q

Staphylococcus aureus bloodstream infections
Extrapolated: 1117 *2016 data are provisional to the end of Q3 only (note: data missing from 2 laboratories for Q3); ‡ 2015 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 proportion of S. aureus bloodstream infections that was meticillin-resistant (i.e. MRSA) decreased to 14.7% in 2016*, the lowest proportion to date The numbers and proportion of MRSA bloodstream infections have been decreasing since 2006 *2016 data provisional to the end of Q3 only EARS-Net data on Antimicrobial Resistance in Ireland, Q

Trends in S. aureus bloodstream infections showing %MRSA *2016 data are provisional to the end of Q3 only (note: data missing from 2 laboratories for Q3); ‡ 2015 missing data from 3 laboratories for 2 quarters each EARS-Net data on Antimicrobial Resistance in Ireland, Q

Distribution of MRSA in EARS-Net countries in 2014
IE rank: 12/29 (19.4%) Median = 13.1% 2014 trends 2 countries 8 countries Map downloaded from ECDC’s TESSy database on 21/10/2015: EARS-Net data on Antimicrobial Resistance in Ireland, Q

Distribution of MRSA in EARS-Net countries in 2014

Trends in S. aureus bloodstream infections (rates)
†Rate per 1,000 bed days used; *2016 data are provisional to the end of Q3 only (note: data missing from 2 laboratories for Q3); ‡ 2015 missing data from 3 laboratories for 2 quarters each Key message: So far in 2016, the %MRSA and MRSA rate are the lowest, while the MSSA rate is the highest reported to date EARS-Net data on Antimicrobial Resistance in Ireland, Q

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

Klebsiella pneumoniae

Klebsiella pneumoniae invasive infections
Extrapolated: *2016 data are provisional to the end of Q3 only (note: data missing from 2 laboratories for Q3); ‡ 2015 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): the proportion of MDRKP among invasive K. pneumoniae infections decreased to 7.4% in 2016* Carbapenem-resistance among K. pneumoniae, particularly as a result of carbapenemase production (see later slide), has been increasing *2016 data provisional to the end of Q3 only EARS-Net data on Antimicrobial Resistance in Ireland, Q

Trends in K. pneumoniae invasive infections showing percentage resistance to fluoroquinolones, aminoglycosides and 3rd-generation cephalosporins *2016 data are provisional to the end of Q3 only (note: data missing from 2 laboratories for Q3); ‡ 2015 missing data from 3 laboratories for 2 quarters each 3GC, 3rd-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, Q

Trends in K. pneumoniae invasive infections with percentage 3GC-resistance and ESBL-positivity *2016 data are provisional to the end of Q3 only (note: data missing from 2 laboratories for Q3); ‡ 2015 missing data from 3 laboratories for 2 quarters each EARS-Net data on Antimicrobial Resistance in Ireland, Q

Distribution of 3rd-generation cephalosporin resistant K. pneumoniae in EARS-Net countries in 2014 IE rank: 21/29 (13.0%) Median = 30.7% 2014 trends 11 countries 5 countries Map downloaded from ECDC’s TESSy database on 21/10/2015: EARS-Net data on Antimicrobial Resistance in Ireland, Q

Carbapenemase-producing K. pneumoniae
Extrapolated: 403 *2016 data are provisional to the end of Q3 only (note: data missing from 2 laboratories for Q3); ‡ 2015 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; CPE, carbapenemase-producing enterobacteriaceae Key messages: In 2016*, the number and proportion of carbapenem-resistant K. pneumoniae have decreased but the overall trend in recent years has been increasing In 2016*, there were 3 confirmed carbapenemase-producing K. pneumoniae from invasive infections compared to 7 in 2015 and just 2 each in 2014 and 2013 Of 18 confirmed carbapenemases to date, 13 were OXA-48 and 5 are KPC EARS-Net data on Antimicrobial Resistance in Ireland, Q

Trends in carbapenemase-producing K. pneumoniae
*2016 data are provisional to the end of Q3 only (note: data missing from 2 laboratories for Q3); ‡ 2015 missing data from 3 laboratories for 2 quarters each; CBP, carbapenem EARS-Net data on Antimicrobial Resistance in Ireland, Q

Distribution of carbapenem-resistant K. pneumoniae in EARS-Net countries in 2014 IE rank: 23/28 (0.6%) Median = 1.3% 2014 trends 7 countries 1 country Map downloaded from ECDC’s TESSy database on 21/10/2015: EARS-Net data on Antimicrobial Resistance in Ireland, Q

Trends in K. pneumoniae invasive infections with percentage multi-drug resistance (MDRKP) *2016 data are provisional to the end of Q3 only (note: data missing from 2 laboratories for Q3); ‡ 2015 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, Q

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

Enterococcus faecium EARS-Net data on Antimicrobial Resistance in Ireland, Q

Enterococcus faecium bloodstream infections
Extrapolated: 425 *2016 data are provisional to the end of Q3 only (note: data missing from 2 laboratories for Q3); ‡ 2015 missing data from 3 laboratories for 2 quarters each: extrapolated figure in 2015 account for missing data using data for the same time period in the previous year Key messages: Since 2012, the proportion of VREfm bloodstream infections has been over 40% Ireland has the highest proportion of VREfm in Europe EARS-Net data on Antimicrobial Resistance in Ireland, Q

Trends in E. faecium bloodstream infections showing %VRE
*2016 data are provisional to the end of Q3 only (note: data missing from 2 laboratories for Q3); ‡ 2015 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, Q

Distribution of vancomycin-resistant E. faecium (VREfm) in EARS-Net countries in 2014 IE rank: 1/29 (45.1%) Median = 4.5% 2014 trends 8 countries 3 countries Map downloaded from ECDC’s TESSy database on 21/10/2015: EARS-Net data on Antimicrobial Resistance in Ireland, Q

Pseudomonas aeruginosa

P. aeruginosa invasive infections
Extrapolated: 209 *2016 data are provisional to the end of Q3 only (note: data missing from 2 laboratories for Q3); ‡ 2015 missing data from 3 laboratories for 2 quarters each: extrapolated figure in 2015 account for missing data using data for the same time period in the previous year Key message: In 2016*, Resistance piperacillin/tazobactam, ceftazidime, fluoroquinolones and aminoglycosides is increasing MDR P. aeruginosa is increasing MDR, Multi-drug resistant (defined as resistance to three or more of the 5 required antibiotics/antibiotic classes: piperacillin-tazobactam; ceftazidime; carbapenems; fluoroquinolones; aminoglycosides) EARS-Net data on Antimicrobial Resistance in Ireland, Q

Trends in P. aeruginosa invasive infections showing percentage resistance to mandatory antibiotics/antibiotic classes (according to EARS-Net protocol) *2016 data are provisional to the end of Q3 only (note: data missing from 2 laboratories for Q3); ‡ 2015 missing data from 3 laboratories for 2 quarters each PIP, piperacillin; TZP, piperacillin/tazobactam; CAZ, ceftazidime; IPM, imipenem; MEM, meropenem (IPM and MEM are carbapenems); CIP, ciprofloxacin; OFX, ofloxacin (CIP and OFX are fluoroquinolones); GEN, gentamicin; TOB, tobramycin and AMK, amikacin (GEN, TOB and AMK are aminoglycosides) EARS-Net data on Antimicrobial Resistance in Ireland, Q

Trends in P. aeruginosa invasive infections with percentage multi-drug resistance (MDR) *2016 data are provisional to the end of Q3 only (note: data missing from 2 laboratories for Q3); ‡ 2015 missing data from 3 laboratories for 2 quarters each MDR, multi-drug resistance defined as resistance to three or more of the 5 required antibiotics/antibiotic classes (piperacillin-tazobactam; ceftazidime; carbapenems; fluoroquinolones; aminoglycosides) EARS-Net data on Antimicrobial Resistance in Ireland, Q

Streptococcus pneumoniae

Streptococcus pneumoniae invasive infections
Extrapolated: 313 *2016 data are provisional to the end of Q3 only (note: data missing from 2 laboratories for Q3); ‡ 2015 missing data from 3 laboratories for 2 quarters each: extrapolated figure in 2015 account for missing data using data for the same time period in the previous year 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 Key messages: The proportions of invasive infections due to PNSP have stabilised at 17-18% since 2014 The numbers that are HLR have decreased since 2011; however, this is partly due to differences in the interpretive criteria as a result of the switchover from CLSI to EUCAST EARS-Net data on Antimicrobial Resistance in Ireland, Q

Trends in S. pneumoniae bloodstream infections showing %PNSP
PCV7 introduced Sept ‘08 PCV13 introduced Dec ‘10 *2016 data are provisional to the end of Q3 only (note: data missing from 2 laboratories for Q3); ‡ 2015 missing data from 3 laboratories for 2 quarters each PNSP, penicillin-non-susceptible S. pneumoniae; I, intermediate; HLR, high-level resistant EARS-Net data on Antimicrobial Resistance in Ireland, Q

Distribution of penicillin-non-susceptible S
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) Map downloaded from ECDC’s TESSy database on 21/10/2015:

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

Pneumococcal serotypes, Q1-3 2016
95% (242/256) pneumococcal isolates were serotyped From patients aged ≥65 years the target population for the PPV23 vaccine), 73% of isolates (96 of 131) were serotypes that are included in the PPV23 vaccine From patients aged <2 years (the target population for the PCV13 vaccine), three (of 12 isolates) were serotypes covered by the vaccine and nine were non-vaccine serotypes The most common serotypes identified were 12F† (n=27), 3*† and 8† (n=25 each), 19A*† (n=24), 33F† (n=18), 22F† (n=14), 9N† (n=13) and 15A (n=10) representing 64% of all isolates typed *PCV13 serotypes; † PPV23 serotypes Serotyping data courtesy of the Irish Pneumococcal Reference Laboratory EARS-Net data on Antimicrobial Resistance in Ireland, Q

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, Q

Additional slides EARS-Net data on Antimicrobial Resistance in Ireland, Q

Summary of resistance trends (selected drug/bug combinations)
*2016 data are provisional to the end of Q3 only EARS-Net data on Antimicrobial Resistance in Ireland, Q

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, Q

Pneumococcal serotypes, 2015
90% (273/304) pneumococcal isolates were serotyped 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 EARS-Net data on Antimicrobial Resistance in Ireland, Q

EARS-Net data on Antimicrobial Resistance in Ireland, Q

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EARS-Net data on Antimicrobial Resistance in Ireland, Q

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