EARS-Net (European Antimicrobial Resistance Surveillance Network) Isolates from 2014, Belgium

Transcription

1 EARS-Net (European Antimicrobial Resistance Surveillance Network) Isolates from 214, Belgium

2 Depot Number : D/215/25/61 PHS Report : WIV-ISP Public health & surveillance Healthcare-associated infections & Antimicrobial resistance Rue Juliette Wytsmanstraat 14 1 Brussels nsih@wiv-isp.be / patrick.verroens@wiv-isp.be Patrick Verroens, Karl Mertens, Sylvanus Fonguh, Anne Ingenbleek, Katrien Latour, Boudewijn Catry November 215; Brussels (Belgium) Page 2 /

3 TABLE OF CONTENT TABLE OF CONTENT SUMMARY INTRODUCTION ABBREVIATIONS ANTIMICROBIAL GROUPS Participation Percentage Bias Incorrect AMR measurement Advised breakpoints Data transfer 8 7. RESULTS National Mean Resistance S. aureus S. pneumonia E. coli K. pneumoniae E. faecalis E. faecium ACKNOWLEDGEMENTS Annex Antimicrobial codes Background on resistance mechanisms 48 Page 3 /

4 1. SUMMARY This report covers the Belgian data (samples from 214) for the European Antimicrobial Resistance surveillance network (EARS-net). Antimicrobial susceptibility profiles of 7 bacterial species (S. aureus, S. pneumoniae, E. faecium, E. faecalis, E. coli, K. pneumoniae, P. aeruginosa) retrieved from blood cultures and cerebrospinal fluid for a selection of antimicrobial agents are provided. The national mean percentage methicillin resistant S. aureus among invasive isolates was 13% while rifampicin and linezolid resistant S. aureus remained below 1%. Penicillines and macrolide resistant S. pneumoniae was 1,4% and 18% respectively. Carbapenem resistance in E. coli and K. pneumoniae remained below 1% while the resistance percentage for other antibiotics against these pathogens is still rather high. E. faecalis and E. faecium vancomycin resistancy are below 1% and around 3% respectiveluy. In P. aeruginosa resistance for carbapenems, ceftazidime and piperacilline was around 1%. 2. INTRODUCTION The European Antimicrobial Resistance Surveillance Network (EARS-net) was founded in 1999 by the Dutch National Institute for Public Health and the Environment (RIVM), but was transferred in early 21 to the European Centre for Disease Control & Prevention (ECDC). The surveillance aims to follow up trends of antimicrobial resistance in bacteria isolated from blood and cerebrospinal fluid (CSF) from clinical laboratories in the Europe union and the European Economic Area. EARS-Net performs antimicrobial resistance (AMR) surveillance for seven bacterial pathogens: Bacterial species Staphylococcus (S.) aureus Streptococcus (S.) pneumoniae Escherichia (E.) coli Klebsiella (K.) pneumonia Enterococcus (E.) faecalis Enterococcus (E.) faecium Pseudomonas (P.) aeruginosa EARS-net code STAAUR STRPNE ESCCOL KLEPNE ENCFAE ENCFAI PSEAER EARS-Net data are exclusively based on invasive isolates (blood or cerebrospinal fluid). This restriction prevents inconsistencies that arise from differences in clinical case definitions, different sampling frames or heterogeneous healthcare utilization that would otherwise confound the data analysis if isolates from all anatomical sources were accepted. However, invasive isolates may for biological reasons not be representative for isolates of the same bacterial species from other sites, i.e. urinary tract infections, pneumonia, wound infections, etcetera. For every patient only the first sample of the year is used in the data (per bacteria). If several samples are taken on the same day, then the sample with the least susceptible result (Resistant>Intermediate>Susceptible; S>I>R) is retained. The coordination of the Belgian branch of EARS-Net is done by the Scientific Institute of Public Health (WIV-ISP), through close collaboration with the clinical microbiology- and national reference laboratories. The time and effort provided by the individual laboratories and teams of hospital hygiene is of great value. Despite EARS-Net is not a mandatory surveillance, the participation rate of laboratories and hospital hygiene teams is high. Further information, including the yearly EARS-net reports can be obtained elsewhere: Page 4 /

5 3. ABBREVIATIONS 3GC AMR AST CI CLSI CSF EARS-Net ECDC ENCFAI ENCFAE ESCCOL EUCAST EQA GLIMS I/R KLEPNE KUL LIMS MIC PSEAER S/I/R STAAUR STRPNE WIV-ISP Third generation cephalosporin s Antimicrobial resistance Antimicrobial susceptibility testing Confidence interval Clinical and Laboratory Standards Institute (USA) Cerebrospinal fluid European Antimicrobial Resistance Surveillance Network European Centre for Disease Prevention and Control, Stockholm Enterococcus faecium Enterococcus faecalis Escherichia coli European Committee on Antimicrobial Susceptibility Testing (EU) External quality assessment Laboratory Information Management System of a particular vendor Intermediary / Resistant Klebsiella pneumoniae Katholieke Universiteit Leuven Laboratory information management system Minimum inhibitory concentration P. aeruginosa Sensitive / Intermediary / Resistant S. aureus S. pneumoniae Wetenschappelijk Instituut Volksgezondheid - Institut Scientifique de Santé Publique Page 5 /

6 4. ANTIMICROBIAL GROUPS The data-collection was organised at antibiotic agent level (e.g. Meropenem, Imipenem). In accordance with the EARSnet international reporting, results are sometimes reported at the level of antibiotics group (e.g. Carbapenems). The least susceptible result (R>I>S) was always retained for each group. The table below shows for each group what antibiotics are included in the present report For all groups, the percentage R or I is reported together in the results. PATHOGEN GROUP NAME ANTIBIOTICS IN THE GROUP 1 ENCFAE/ENCFAI Aminopenicillins AMOXICILLIN, AMPICILLIN ENCFAE/ENCFAI High level gentamicin GENTAMICINTAMICIN-HIGH ENCFAE/ENCFAI Glycopeptides VANCOMYCIN, TEICOPLANIN ENCFAE/ENCFAI Linezolid LINEZOLID ESCCOL Aminopenicillins AMOXICILLIN, AMPICILLIN ESCCOL/KLEPNE 3rd gen. cephalosporins CEFOTAXIME, CEFTRIAXONE, CEFTAZIDIME ESCCOL/KLEPNE Aminoglycosides AMIKACIN, GENTAMICIN, TOBRAMYCIN ESCCOL/KLEPNE Fluoroquinolones CIPROFLOXACIN, OFLOXACIN, LEVOFLOXACIN ESCCOL/KLEPNE Carbapenems IMIPENEM, MEROPENEM PSEAER Piperacillin±tazobactam PIPERACILLIN, PIPERACILLIN/TAZOBACTAM PSEAER Ceftazidime CEFTAZIDIME PSEAER Aminoglycosides GENTAMICIN, TOBRAMYCIN PSEAER Amikacin AMIKACIN PSEAER Fluoroquinolones CIPROFLOXACIN, LEVOFLOXACIN PSEAER Carbapenems IMIPENEM, MEROPENEM STAAUR MRSA METHICILLIN, OXACILLIN, CEFOXITIN, FLUCLOXACILLIN, CLOXACILLIN, DICLOXACILLIN STAAUR Fluoroquinolones CIPROFLOXACIN, OFLOXACIN, LEVOFLOXACIN, NORFLOXACIN STAAUR Rifampin RIFAMPIN STAAUR Linezolid LINEZOLID STRPNE Penicillins PENICILLIN G, OXACILLIN STRPNE Macrolides ERYTHROMYCIN, CLARITHROMYCIN, AZITHROMYCIN STRPNE 3rd gen. cephalosporins CEFOTAXIME, CEFTRIAXONE STRPNE Fluoroquinolones CIPROFLOXACIN, OFLOXACIN, LEVOFLOXACIN, NORFLOXACIN STRPNE Moxifloxacin MOXIFLOXACIN 1 ECDC codes are used. See annex for explanation. Page 6 /

7 5. Participation Percentage The participation percentages were calculated by dividing for each pathogen the number of participating hospital laboratories divided by the total number of microbial hospital laboratories of that year. Historical hospital laboratory participation percentages for each pathogen. Since 27, the number of hospital labs for microbiology decreased from 111 in the year 27 to 16 in 214. The high participation percentage for S. Pneumoniae was possible thanks to the data-collection efforts performed by and communicated to the reference lab KULeuven university (see acknowledgements). Table 1 Hospital microbiology laboratory participation percentages to the EARS-Net program Year S. pneumoniae S. aureus Enterococci E. coli K. pneumoniae P. aeruginosa Page 7 /

8 6. Bias Measurement bias for antimicrobial susceptibility testing (AST) occurs when the registered results for an isolate are not valid for that isolate. In other words: the measured result does not accurately reflect the true value of that isolate. Since measurement bias has serious consequences for validity, it is important to assess it. In our setting there are 3 possibilities for measurement error: incorrect measurement during the AST not using advised breakpoints during AST incorrect data transfer Above is under the assumption that a proper bacterial species identification is done, since intrinsic susceptibility results largely vary according to the bacterial species. 6.1 Incorrect AMR measurement The quality of measurement can be assessed in several ways: Comparing the result with the result of a gold standard test assessment of the prediction model that is created with the study measurements (a good model is an argument against measurement bias but the opposite cannot be concluded) assessment of the repeatability (bad repeatability implies there is measurement bias but the opposite cannot be concluded) EARS-Net EQA In EARS-Net external quality assessment (EQA) is used. In the EQA a lab is sent several samples that they are asked to identify and provide AMR test results for. If the identification is done correctly, the AST results are compared to the results of the gold standard (which is the result of reference labs). 6.2 Advised breakpoints WIV-ISP and BAPCOC encourage the use of EUCAST breakpoints but not every lab in Belgium uses EUCAST, approximately % of labs use CLSI and about 4% are using EUCAST (estimation year 21). The MIC breakpoints are very close in certain cases, but can be relatively far from each other in other cases. 6.3 Data transfer Methodology Currently only the electronic method is used, meaning a transfer of a xml, csv or xls file. These files are created either using a GLIMS query or a custom made query (e.g. in InfoPartner) that extracts the GLIMS data into a standard format. After the data are transformed into the TESSy format (ECDC standard), results are resent to the labs in order to discover errors in ether hospital GLIMS or the query (validation). After validation the data are introduced into the central database on a secure WIV-ISP server. Discussion Every data extraction, -transfer or manipulation as well as each validation step leaves room for human error. We assume electronic methods according to good practises in combination with the validation step helps reducing this error to a level as minimal as possible. Page 8 /

9 7. RESULTS The results are presented in a national overview (table 2) as well as in graphs of the corresponding bug-drug combination. The absolute numbers can be found in the horizontal axis of every graph. If a lab did not send a certain bug-drug combination (zero cases of AB not tested) then it is not in the graph of that combination. Confidence intervals (CI) are necessary to keep in mind, even though a lab sends all of its data. This can easily be illustrated with a hypothetical example of a lab that has 1 patient with Streptococcus, with results R in penicillin susceptibility. The result is % resistance. Obviously this % has a large margin of error, due to the low sample size. CI were not given in the graph, because the graphs become difficult to read in that case. Despite the electronic support, lack of standardisation of incoming data as well as available reference data are a difficulty and could have influenced the quality further in the information stream. Following for example SNOMED-CT standards can probably help to improve this in future. Page 9 /

10 National Mean Resistance Table 2 Calculated national mean resistance percentages Pathogen Resistance I / R S Total Mean I/R (%) STAAUR Fluoroquinolones Glycopeptides Linezolid <1 Meticillin Rifampin <1 STRPNE 3GC <.1 Fluoroquinolones <.1 Macrolides Moxifloxacin Penicilines ESCCOL 3GC Aminoglycosides Aminopenicillins Carbapenems <.1 Fluoroquinolones KLEPNE 3GC Aminoglycosides Carbapenems <1 Fluoroquinolones ENCFAE Aminopenicillins <1 High-levelgentamicine Linezolid Teicoplanin <1 Vancomycine <1 ENCFAI Aminopenicillins High-levelgentamicine Linezolid Teicoplanin Vancomycine PSEAER Amikacin Aminoglycosides Carbapenems Ceftazidime Fluoroquinolones Piperacillin(+tazo) Page 1 /

11 7.1 S. aureus Figure S. aureus resistance percentage by lab to fluoroquinolones grouping the antibiotics CIPROFLOXACIN, OFLOXACIN, LEVOFLOXACIN, NORFLOXACIN Page 11 /

12 BE11 ( / 44 ) BE12 ( / 1 ) BE31 ( / 16 ) BE61 ( / 9 ) BE12 ( / 28 ) BE171 ( / 19 ) BE241 ( / 41 ) BE371 ( / 16 ) BE441 ( / 26 ) BE45X ( / 53 ) BE48x ( / 18 ) BE57x ( / 7 ) BE61X ( / 9 ) BE631 ( / 48 ) BE74X ( / 73 ) BE751 ( / 42 ) BE771 ( / 59 ) BE1121 ( / 39 ) BE1141 ( / 17 ) BE1251 ( / 5 ) BE1291 ( / 74 ) BE11 ( / 9 ) BE1641 ( / 11 ) BE11 ( / 21 ) BE971 ( 1 / 58 ) EARS-Net susceptibility test results: Linezolid and STAAUR in *A low number of samples (e.g. <1) means percentages should be interpreted with caution due to large Confidence Intervals. For the selection of Antibiotics behind each group see EARS-Net protocol Page 12 /

13 BE441 ( / 26 ) BE751 ( 2 / 44 ) BE31 ( 1 / 16 ) BE771 ( 4 / 59 ) BE12 ( 2 / 28 ) BE1 ( 5 / 69 ) BE61X ( 7 / 75 ) BE1121 ( 5 / 47 ) BE11 ( 1 / 9 ) BE1141 ( 2 / 17 ) BE45X ( 7 / 59 ) BE631 ( 6 / 49 ) BE371 ( 2 / 16 ) BE11 ( 6 / 45 ) BE561 ( 12 / ) BE74X ( 1 / 73 ) BE1641 ( 2 / 12 ) BE241 ( 7 / 41 ) BE61 ( 9 / 45 ) BE1291 ( 17 / 74 ) BE971 ( 14 / 58 ) BE1251 ( 3 / 11 ) BE171 ( 6 / 2 ) BE71 ( 3 / 9 ) EARS-Net susceptibility test results: Meticillin and STAAUR in *A low number of samples (e.g. <1) means percentages should be interpreted with caution due to large Confidence Intervals. For the selection of Antibiotics behind each group see EARS-Net protocol Page 13 /

14 BE11 ( / 45 ) BE31 ( / 1 ) BE61 ( / 45 ) BE71 ( / 2 ) BE12 ( / 28 ) BE171 ( / 19 ) BE241 ( / 2 ) BE61X ( / 8 ) BE74X ( / 73 ) BE751 ( / 42 ) BE771 ( / 59 ) BE1121 ( / 39 ) BE1141 ( / 17 ) BE1251 ( / 5 ) BE11 ( / 9 ) BE1641 ( / 11 ) BE45X ( 1 / 47 ) BE1291 ( 1 / 7 ) EARS-Net susceptibility test results: Rifampin and STAAUR in *A low number of samples (e.g. <1) means percentages should be interpreted with caution due to large Confidence Intervals. For the selection of Antibiotics behind each group see EARS-Net protocol Page 14 /

15 BE11 ( / 15 ) BE21 ( / 28 ) BE31 ( / 7 ) BE41 ( / 12 ) BE61 ( / 17 ) BE71 ( / 6 ) BE81 ( / 22 ) BE91 ( / 5 ) BE11 ( / 6 ) BE111 ( / 28 ) BE12 ( / 9 ) BE141 ( / 5 ) BE161 ( / 13 ) BE171 ( / 1 ) BE181 ( / 7 ) BE191 ( / 12 ) BE211 ( / 14 ) BE221 ( / 27 ) BE231 ( / 16 ) BE241 ( / 23 ) BE261 ( / 13 ) BE291 ( / 6 ) BE31 ( / 11 ) BE311 ( / 1 ) BE321 ( / 17 ) BE331 ( / 4 ) BE351 ( / 1 ) BE431 ( / 34 ) BE441 ( / 2 ) BE45X ( / 3 ) BE461 ( / 13 ) BE48x ( / 18 ) BE491 ( / 1 ) BE511 ( / 1 ) BE541 ( / 15 ) BE561 ( / 1 ) BE57x ( / 1 ) BE1 ( / 19 ) BE631 ( / 17 ) BE691 ( / 8 ) BE1 ( / 27 ) BE711 ( / 12 ) BE721 ( / 1 ) BE731 ( / 1 ) BE751 ( / 25 ) BE771 ( / 25 ) BE811 ( / 4 ) BE831 ( / 5 ) BE841 ( / 13 ) BE1 ( / 11 ) BE911 ( / 23 ) BE921 ( / 29 ) BE931 ( / 2 ) BE951 ( / 9 ) BE981 ( / 5 ) BE1 ( / 6 ) BE111 ( / 16 ) BE121 ( / 15 ) BE131 ( / 5 ) BE141 ( / 15 ) BE151 ( / 9 ) BE161 ( / 1 ) BE171 ( / 8 ) BE181 ( / 49 ) BE191 ( / 6 ) BE111 ( / 7 ) BE1131 ( / 23 ) BE1141 ( / 1 ) BE1151 ( / 11 ) BE1161 ( / 14 ) BE1181 ( / 7 ) BE1251 ( / 6 ) BE1291 ( / 17 ) BE1371 ( / 2 ) BE1391 ( / 5 ) BE1411 ( / 8 ) BE1431 ( / 16 ) BE1461 ( / 8 ) BE1521 ( / 3 ) BE1531 ( / 3 ) BE1541 ( / 11 ) BE1561 ( / 3 ) BE11 ( / 7 ) BE1611 ( / 9 ) BE1641 ( / 7 ) BE1651 ( / 1 ) BE1661 ( / 7 ) BE11 ( / 3 ) BE1711 ( / 8 ) BE1741 ( / 1 ) BE51 ( 1 / 11 ) 7.2 S. pneumonia EARS-Net susceptibility test results: 3GC and STRPNE in *A low number of samples (e.g. <1) means percentages should be interpreted with caution due to large Confidence Intervals. For the selection of Antibiotics behind each group see EARS-Net protocol Figure S. pneumoniae resistance percentage by lab to third generation cephalosporins grouping the antibiotics CEFOTAXIME and CEFTRIAXONE Page 15 /

16 BE11 ( / 15 ) BE21 ( / 28 ) BE31 ( / 7 ) BE41 ( / 12 ) BE51 ( / 11 ) BE61 ( / 11 ) BE81 ( / 22 ) BE91 ( / 5 ) BE11 ( / 6 ) BE111 ( / 28 ) BE12 ( / 9 ) BE141 ( / 5 ) BE161 ( / 13 ) BE181 ( / 7 ) BE191 ( / 12 ) BE211 ( / 14 ) BE221 ( / 27 ) BE231 ( / 16 ) BE261 ( / 13 ) BE291 ( / 6 ) BE31 ( / 12 ) BE311 ( / 1 ) BE321 ( / 17 ) BE331 ( / 4 ) BE351 ( / 1 ) BE431 ( / 35 ) BE441 ( / 2 ) BE45X ( / 28 ) BE461 ( / 13 ) BE48x ( / 18 ) BE491 ( / 1 ) BE511 ( / 1 ) BE541 ( / 15 ) BE561 ( / 1 ) BE57x ( / 1 ) BE691 ( / 8 ) BE1 ( / 27 ) BE711 ( / 12 ) BE721 ( / 1 ) BE731 ( / 1 ) BE751 ( / 24 ) BE771 ( / 25 ) BE811 ( / 4 ) BE831 ( / 5 ) BE841 ( / 13 ) BE1 ( / 11 ) BE911 ( / 23 ) BE921 ( / 29 ) BE931 ( / 2 ) BE951 ( / 9 ) BE981 ( / 5 ) BE1 ( / 6 ) BE111 ( / 16 ) BE121 ( / 15 ) BE131 ( / 5 ) BE141 ( / 15 ) BE151 ( / 9 ) BE161 ( / 1 ) BE171 ( / 8 ) BE181 ( / 49 ) BE191 ( / 6 ) BE111 ( / 7 ) BE1121 ( / 31 ) BE1141 ( / 1 ) BE1151 ( / 11 ) BE1161 ( / 14 ) BE1181 ( / 7 ) BE1251 ( / 7 ) BE1291 ( / 17 ) BE1371 ( / 2 ) BE1391 ( / 5 ) BE1411 ( / 8 ) BE1431 ( / 16 ) BE1461 ( / 8 ) BE1521 ( / 3 ) BE1531 ( / 3 ) BE1541 ( / 11 ) BE1561 ( / 3 ) BE11 ( / 7 ) BE1611 ( / 9 ) BE1641 ( / 7 ) BE1651 ( / 1 ) BE1661 ( / 7 ) BE11 ( / 3 ) BE1711 ( / 8 ) BE1741 ( / 1 ) BE1131 ( 1 / 23 ) EARS-Net susceptibility test results: Fluoroquinolones and STRPNE in *A low number of samples (e.g. <1) means percentages should be interpreted with caution due to large Confidence Intervals. For the selection of Antibiotics behind each group see EARS-Net protocol Figure S. pneumoniae resistance percentage by lab to fluoroquinolones grouping the antibiotics CIPROFLOXACIN, OFLOXACIN, LEVOFLOXACIN, NORFLOXACIN Page 16 /

17 BE21 ( / 28 ) BE31 ( / 7 ) BE91 ( / 5 ) BE141 ( / 5 ) BE181 ( / 7 ) BE311 ( / 1 ) BE351 ( / 1 ) BE561 ( / 1 ) BE57x ( / 1 ) BE731 ( / 1 ) BE951 ( / 9 ) BE131 ( / 5 ) BE161 ( / 1 ) BE1371 ( / 2 ) BE1391 ( / 5 ) BE1521 ( / 3 ) BE1561 ( / 3 ) BE1651 ( / 1 ) BE11 ( / 3 ) BE1741 ( / 1 ) BE771 ( 1 / 25 ) BE48x ( 1 / 18 ) BE541 ( 1 / 15 ) BE45X ( 2 / 29 ) BE211 ( 1 / 14 ) BE191 ( 1 / 12 ) BE31 ( 1 / 12 ) BE911 ( 2 / 23 ) BE371 ( 1 / 1 ) BE491 ( 1 / 1 ) BE1 ( 2 / 2 ) BE151 ( 1 / 9 ) BE321 ( 2 / 17 ) BE171 ( 1 / 8 ) BE1431 ( 2 / 16 ) BE1461 ( 1 / 8 ) BE1711 ( 1 / 8 ) BE241 ( 3 / 23 ) BE74X ( 2 / 15 ) BE81 ( 3 / 22 ) BE111 ( 4 / 28 ) BE111 ( 1 / 7 ) BE1161 ( 2 / 14 ) BE11 ( 1 / 7 ) BE221 ( 4 / 27 ) BE41 ( 2 / 12 ) BE11 ( 1 / 6 ) BE1 ( 1 / 6 ) BE431 ( 6 / 35 ) BE1131 ( 4 / 23 ) BE1291 ( 3 / 17 ) BE1 ( 2 / 11 ) BE111 ( 3 / 16 ) BE831 ( 1 / 5 ) BE931 ( 4 / 2 ) BE141 ( 3 / 15 ) BE1141 ( 2 / 1 ) BE921 ( 6 / 29 ) BE1 ( 6 / 27 ) BE1611 ( 2 / 9 ) BE181 ( 11 / 49 ) BE261 ( 3 / 13 ) BE841 ( 3 / 13 ) BE61 ( 4 / 17 ) BE631 ( 4 / 17 ) BE231 ( 4 / 16 ) BE331 ( 1 / 4 ) BE691 ( 2 / 8 ) BE711 ( 3 / 12 ) BE811 ( 1 / 4 ) BE1411 ( 2 / 8 ) BE121 ( 4 / 15 ) BE1151 ( 3 / 11 ) BE1541 ( 3 / 11 ) BE1251 ( 2 / 7 ) BE1661 ( 2 / 7 ) BE511 ( 3 / 1 ) BE721 ( 3 / 1 ) BE461 ( 4 / 13 ) BE11 ( 5 / 15 ) BE71 ( 2 / 6 ) BE12 ( 3 / 9 ) BE171 ( 1 / 3 ) BE291 ( 2 / 6 ) BE1531 ( 1 / 3 ) BE51 ( 4 / 11 ) BE981 ( 2 / 5 ) BE1641 ( 3 / 7 ) BE751 ( 11 / 24 ) BE161 ( 6 / 13 ) BE441 ( 1 / 2 ) BE191 ( 3 / 6 ) BE1181 ( 4 / 7 ) EARS-Net susceptibility test results: Macrolides and STRPNE in *A low number of samples (e.g. <1) means percentages should be interpreted with caution due to large Confidence Intervals. For the selection of Antibiotics behind each group see EARS-Net protocol Figure S. pneumoniae resistance percentage by lab to macrolides grouping the antibiotics ERYTHROMYCIN, CLARITHROMYCIN, AZITHROMYCIN Page 17 /

18 BE71 ( / 6 ) BE241 ( / 23 ) BE371 ( / 1 ) BE45X ( / 3 ) BE48x ( / 18 ) BE57x ( / 1 ) BE631 ( / 17 ) BE74X ( / 14 ) BE751 ( / 1 ) BE1251 ( / 7 ) EARS-Net susceptibility test results: Moxifloxacin and STRPNE in *A low number of samples (e.g. <1) means percentages should be interpreted with caution due to large Confidence Intervals. For the selection of Antibiotics behind each group see EARS-Net protocol Page 18 /

19 BE11 ( / 15 ) BE21 ( / 28 ) BE31 ( / 7 ) BE41 ( / 12 ) BE51 ( / 11 ) BE61 ( / 14 ) BE81 ( / 22 ) BE91 ( / 5 ) BE11 ( / 6 ) BE111 ( / 28 ) BE12 ( / 9 ) BE141 ( / 5 ) BE161 ( / 13 ) BE181 ( / 7 ) BE191 ( / 12 ) BE211 ( / 14 ) BE221 ( / 27 ) BE231 ( / 16 ) BE261 ( / 13 ) BE291 ( / 6 ) BE31 ( / 12 ) BE311 ( / 1 ) BE321 ( / 17 ) BE331 ( / 4 ) BE351 ( / 1 ) BE371 ( / 1 ) BE431 ( / 35 ) BE441 ( / 2 ) BE461 ( / 13 ) BE48x ( / 18 ) BE491 ( / 1 ) BE511 ( / 1 ) BE541 ( / 15 ) BE561 ( / 1 ) BE57x ( / 1 ) BE61X ( / 22 ) BE691 ( / 8 ) BE1 ( / 27 ) BE711 ( / 12 ) BE721 ( / 1 ) BE731 ( / 1 ) BE771 ( / 25 ) BE811 ( / 4 ) BE831 ( / 5 ) BE841 ( / 13 ) BE1 ( / 11 ) BE911 ( / 23 ) BE921 ( / 29 ) BE931 ( / 2 ) BE951 ( / 9 ) BE981 ( / 5 ) BE1 ( / 6 ) BE111 ( / 16 ) BE121 ( / 15 ) BE131 ( / 5 ) BE141 ( / 15 ) BE151 ( / 9 ) BE161 ( / 1 ) BE171 ( / 8 ) BE191 ( / 6 ) BE111 ( / 7 ) BE1131 ( / 23 ) BE1141 ( / 1 ) BE1151 ( / 11 ) BE1181 ( / 7 ) BE1251 ( / 6 ) BE1291 ( / 17 ) BE1371 ( / 2 ) BE1391 ( / 5 ) BE1411 ( / 8 ) BE1431 ( / 16 ) BE1461 ( / 8 ) BE1521 ( / 3 ) BE1531 ( / 3 ) BE1541 ( / 11 ) BE1561 ( / 3 ) BE11 ( / 7 ) BE1611 ( / 9 ) BE1641 ( / 7 ) BE1651 ( / 1 ) BE1661 ( / 7 ) BE11 ( / 3 ) BE1711 ( / 8 ) BE1741 ( / 1 ) BE181 ( 1 / 49 ) BE751 ( 1 / 24 ) BE631 ( 1 / 17 ) BE1161 ( 1 / 14 ) BE1 ( 2 / 2 ) BE971 ( 2 / 19 ) BE241 ( 3 / 23 ) BE71 ( 1 / 6 ) BE74X ( 2 / 9 ) BE171 ( 1 / 3 ) EARS-Net susceptibility test results: Penicilines and STRPNE in *A low number of samples (e.g. <1) means percentages should be interpreted with caution due to large Confidence Intervals. For the selection of Antibiotics behind each group see EARS-Net protocol Figure S. pneumoniae resistance percentage by lab to penicillines grouping the antibiotics PENICILLIN G, OXACILLIN Page 19 /

20 BE11 ( / 129 ) BE12 ( / 1 ) BE31 ( / 74 ) BE61 ( / 112 ) BE71 ( / 65 ) BE12 ( / 65 ) BE241 ( / 151 ) BE371 ( / 63 ) BE441 ( / 93 ) BE45X ( / 192 ) BE48x ( / ) BE561 ( / 296 ) BE57x ( / 6 ) BE1 ( / 11 ) BE61X ( / 145 ) BE631 ( / 177 ) BE74X ( / 78 ) BE751 ( / 124 ) BE1121 ( / 128 ) BE1141 ( / 55 ) BE1251 ( / 26 ) BE1291 ( / 13 ) BE11 ( / 28 ) BE1641 ( / 36 ) BE11 ( / 67 ) BE771 ( 1 / 22 ) 7.3 E. coli EARS-Net susceptibility test results: Carbapenems and ESCCOL in *A low number of samples (e.g. <1) means percentages should be interpreted with caution due to large Confidence Intervals. For the selection of Antibiotics behind each group see EARS-Net protocol Figure E. coli resistance percentage by lab to carbapenems grouping the antibiotics IMIPENEM, MEROPENEM Page 2 /

21 BE57x ( / 6 ) BE1251 ( 3 / 26 ) BE371 ( 1 / 63 ) BE11 ( 24 / 129 ) BE61 ( 25 / 113 ) BE1121 ( 29 / 128 ) BE171 ( 16 / 69 ) BE441 ( 22 / 93 ) BE241 ( 36 / 152 ) BE45X ( 47 / 192 ) BE1641 ( 9 / 36 ) BE31 ( 19 / 74 ) BE48x ( 13 / ) BE71 ( 17 / 65 ) BE61X ( 39 / 145 ) BE751 ( 42 / 153 ) BE11 ( 8 / 28 ) BE1 ( 32 / 11 ) BE1141 ( 16 / 55 ) BE771 ( 59 / 22 ) BE971 ( 63 / 21 ) BE631 ( 54 / 179 ) BE74X ( 24 / 78 ) BE11 ( 21 / 67 ) BE12 ( 21 / 65 ) BE1291 ( 48 / 131 ) BE12 ( 5 / 1 ) EARS-Net susceptibility test results: Fluoroquinolones and ESCCOL in *A low number of samples (e.g. <1) means percentages should be interpreted with caution due to large Confidence Intervals. For the selection of Antibiotics behind each group see EARS-Net protocol Figure E. coli resistance percentage by lab to fluoroquinolones grouping the antibiotics CIPROFLOXACIN, OFLOXACIN, LEVOFLOXACIN Page 21 /

22 BE441 ( 44 / 93 ) BE561 ( 144 / 2 ) BE12 ( 5 / 1 ) BE11 ( 14 / 28 ) BE1641 ( 18 / 36 ) BE241 ( 79 / 152 ) BE371 ( 33 / 63 ) BE1251 ( 14 / 26 ) BE48x ( 27 / ) BE1 ( 53 / 97 ) BE751 ( 68 / 124 ) BE11 ( 75 / 129 ) BE11 ( 39 / 67 ) BE771 ( 118 / 22 ) BE631 ( 16 / 177 ) BE61X ( 87 / 145 ) BE45X ( 117 / 192 ) BE31 ( 46 / 74 ) BE1121 ( / 128 ) BE61 ( 71 / 113 ) BE71 ( 41 / 65 ) BE12 ( 41 / 65 ) BE1291 ( 82 / 13 ) BE57x ( 4 / 6 ) BE971 ( 142 / 21 ) BE74X ( 54 / 78 ) BE1141 ( 39 / 55 ) BE171 ( 52 / 69 ) EARS-Net susceptibility test results: Aminopenicillins and ESCCOL in *A low number of samples (e.g. <1) means percentages should be interpreted with caution due to large Confidence Intervals. For the selection of Antibiotics behind each group see EARS-Net protocol Figure E. coli resistance percentage by lab to aminopenicillins grouping the antibiotics AMOXICILLIN, AMPICILLIN Page 22 /

23 BE371 ( / 63 ) BE441 ( / 93 ) BE57x ( / 6 ) BE1 ( / 11 ) BE1251 ( 1 / 26 ) BE751 ( 9 / 158 ) BE45X ( 11 / 192 ) BE61 ( 8 / 116 ) BE1121 ( 9 / 128 ) BE11 ( 2 / 28 ) BE61X ( 11 / 145 ) BE71 ( 5 / 65 ) BE74X ( 6 / 78 ) BE48x ( 4 / ) BE11 ( 7 / 85 ) BE11 ( 11 / 129 ) BE771 ( 18 / 22 ) BE631 ( 16 / 177 ) BE1291 ( 14 / 1 ) BE241 ( 15 / 152 ) BE1141 ( 6 / 56 ) BE1641 ( 4 / 36 ) BE12 ( 1 / 65 ) BE31 ( 12 / 75 ) BE12 ( 4 / 1 ) EARS-Net susceptibility test results: Aminoglycosides and ESCCOL in *A low number of samples (e.g. <1) means percentages should be interpreted with caution due to large Confidence Intervals. For the selection of Antibiotics behind each group see EARS-Net protocol Figure: E. coli resistance percentage by lab to aminoglycosides grouping the antibiotics AMIKACIN, GENTAMICIN, TOBRAMYCIN Page 23 /

24 BE57x ( / 6 ) BE1251 ( / 26 ) BE561 ( 5 / 311 ) BE1141 ( 2 / 55 ) BE441 ( 4 / 93 ) BE771 ( 1 / 22 ) BE751 ( 9 / 167 ) BE11 ( 1 / 13 ) BE71 ( 5 / 65 ) BE45X ( 16 / 192 ) BE1121 ( 11 / 128 ) BE11 ( 7 / 81 ) BE371 ( 6 / 63 ) BE241 ( 15 / 152 ) BE48x ( 5 / ) BE171 ( 7 / 69 ) BE61 ( 13 / 116 ) BE1291 ( 19 / 144 ) BE971 ( 28 / 21 ) BE631 ( 24 / 179 ) BE61X ( 2 / 145 ) BE11 ( 4 / 28 ) BE74X ( 13 / 79 ) BE1 ( 3 / 17 ) BE12 ( 12 / 65 ) BE31 ( 16 / 74 ) BE1641 ( 8 / 36 ) BE12 ( 4 / 1 ) EARS-Net susceptibility test results: 3GC and ESCCOL in *A low number of samples (e.g. <1) means percentages should be interpreted with caution due to large Confidence Intervals. For the selection of Antibiotics behind each group see EARS-Net protocol Figure : E. coli resistance percentage by lab to third generation cephalosporins grouping the antibiotics CEFOTAXIME, CEFTRIAXONE, CEFTAZIDIME Page 24 /

25 BE12 ( / 2 ) BE71 ( / 5 ) BE241 ( / 12 ) BE57x ( / 1 ) BE631 ( / 21 ) BE1251 ( / 4 ) BE11 ( / 5 ) BE1641 ( / 6 ) BE441 ( 1 / 12 ) BE751 ( 2 / 24 ) BE1 ( 2 / 23 ) BE11 ( 2 / 21 ) BE31 ( 1 / 8 ) BE561 ( 7 / 55 ) BE48x ( 1 / 7 ) BE74X ( 7 / 41 ) BE45X ( 5 / 28 ) BE371 ( 2 / 11 ) BE971 ( 1 / 54 ) BE61X ( 5 / 23 ) BE171 ( 5 / 22 ) BE12 ( 3 / 12 ) BE1291 ( 5 / 2 ) BE11 ( 2 / 7 ) BE771 ( 23 / 69 ) BE1141 ( 2 / 5 ) BE1121 ( 7 / 15 ) Percentage* 7.4 K. pneumoniae EARS-Net susceptibility test results: Fluoroquinolones and KLEPNE in *A low number of samples (e.g. <1) means percentages should be interpreted with caution due to large Confidence Intervals. For the selection of Antibiotics behind each group see EARS-Net protocol Figure : K. pneumonia resistance percentage by lab to fluoroquinolones grouping the antibiotics CIPROFLOXACIN, OFLOXACIN, LEVOFLOXACIN Page 25 /

26 BE11 ( / 21 ) BE12 ( / 2 ) BE31 ( / 8 ) BE71 ( / 5 ) BE12 ( / 12 ) BE241 ( / 12 ) BE371 ( / 11 ) BE441 ( / 12 ) BE45X ( / 28 ) BE48x ( / 7 ) BE57x ( / 1 ) BE1 ( / 23 ) BE61X ( / 23 ) BE631 ( / 21 ) BE74X ( / 41 ) BE751 ( / 17 ) BE771 ( / 69 ) BE1121 ( / 15 ) BE1141 ( / 5 ) BE1251 ( / 4 ) BE1291 ( / 2 ) BE11 ( / 5 ) BE1641 ( / 6 ) BE11 ( / 7 ) BE561 ( 2 / 54 ) EARS-Net susceptibility test results: Carbapenems and KLEPNE in *A low number of samples (e.g. <1) means percentages should be interpreted with caution due to large Confidence Intervals. For the selection of Antibiotics behind each group see EARS-Net protocol Figure : K. pneumoniae resistance percentage by lab to carbapenems grouping the antibiotics IMIPENEM, MEROPENEM Page 26 /

27 BE12 ( / 2 ) BE71 ( / 5 ) BE12 ( / 12 ) BE241 ( / 12 ) BE371 ( / 11 ) BE48x ( / 7 ) BE57x ( / 1 ) BE1 ( / 23 ) BE631 ( / 21 ) BE1141 ( / 5 ) BE1251 ( / 4 ) BE11 ( / 5 ) BE1641 ( / 6 ) BE11 ( / 1 ) BE751 ( 1 / 23 ) BE11 ( 1 / 21 ) BE441 ( 1 / 12 ) BE61X ( 2 / 23 ) BE31 ( 1 / 8 ) BE45X ( 4 / 28 ) BE74X ( 7 / 41 ) BE1291 ( 4 / 21 ) BE1121 ( 3 / 15 ) BE771 ( 14 / 69 ) EARS-Net susceptibility test results: Aminoglycosides and KLEPNE in *A low number of samples (e.g. <1) means percentages should be interpreted with caution due to large Confidence Intervals. For the selection of Antibiotics behind each group see EARS-Net protocol Figure : K. pneumoniae resistance percentage by lab to aminoglycosides grouping the antibiotics AMIKACIN, GENTAMICIN, TOBRAMYCIN Page 27 /

28 BE12 ( / 2 ) BE71 ( / 5 ) BE48x ( / 7 ) BE57x ( / 1 ) BE1 ( / 2 ) BE1251 ( / 4 ) BE11 ( / 5 ) BE1641 ( / 6 ) BE561 ( 2 / 59 ) BE751 ( 1 / 26 ) BE631 ( 1 / 21 ) BE241 ( 1 / 12 ) BE441 ( 1 / 12 ) BE31 ( 1 / 8 ) BE11 ( 3 / 21 ) BE12 ( 2 / 12 ) BE61X ( 4 / 23 ) BE371 ( 2 / 11 ) BE1121 ( 3 / 15 ) BE771 ( 14 / 69 ) BE45X ( 6 / 28 ) BE171 ( 5 / 22 ) BE1291 ( 5 / 22 ) BE971 ( 13 / 54 ) BE74X ( 11 / 41 ) BE11 ( 3 / 9 ) BE1141 ( 2 / 5 ) EARS-Net susceptibility test results: 3GC and KLEPNE in *A low number of samples (e.g. <1) means percentages should be interpreted with caution due to large Confidence Intervals. For the selection of Antibiotics behind each group see EARS-Net protocol Figure : K. pneumoniae resistance percentage by lab to third generation cephalosporins grouping the antibiotics CEFOTAXIME, CEFTRIAXONE, CEFTAZIDIME Page 28 /

29 BE11 ( / 13 ) BE31 ( / 9 ) BE61 ( / 12 ) BE71 ( / 3 ) BE171 ( / 15 ) BE241 ( / 13 ) BE371 ( / 4 ) BE45X ( / 33 ) BE48x ( / 3 ) BE561 ( / 28 ) BE1 ( / 17 ) BE61X ( / 3 ) BE631 ( / 22 ) BE751 ( / 11 ) BE771 ( / 32 ) BE971 ( / 36 ) BE1121 ( / 14 ) BE1141 ( / 9 ) BE1251 ( / 4 ) BE1291 ( / 15 ) BE11 ( / 2 ) BE1641 ( / 5 ) BE11 ( / 11 ) BE74X ( 1 / 12 ) 7.5 E. faecalis EARS-Net susceptibility test results: Aminopenicillins and ENCFAE in *A low number of samples (e.g. <1) means percentages should be interpreted with caution due to large Confidence Intervals. For the selection of Antibiotics behind each group see EARS-Net protocol Figure : E. faecalis resistance percentage by lab to aminopenicillins grouping the antibiotics AMOXICILLIN, AMPICILLIN Page 29 /

30 BE371 ( / 3 ) BE74X ( / 8 ) BE61 ( 1 / 12 ) BE31 ( 1 / 9 ) BE1 ( 2 / 15 ) BE751 ( 2 / 1 ) BE45X ( 8 / 33 ) BE1251 ( 1 / 4 ) BE1291 ( 4 / 14 ) BE771 ( 9 / 31 ) BE71 ( 1 / 3 ) BE1141 ( 3 / 9 ) BE1121 ( 5 / 14 ) BE1641 ( 2 / 5 ) EARS-Net susceptibility test results: High-level genta and ENCFAE in *A low number of samples (e.g. <1) means percentages should be interpreted with caution due to large Confidence Intervals. For the selection of Antibiotics behind each group see EARS-Net protocol Page 3 /

31 BE11 ( / 13 ) BE31 ( / 9 ) BE61 ( / 4 ) BE171 ( / 13 ) BE241 ( / 13 ) BE371 ( / 4 ) BE441 ( / 11 ) BE45X ( / 33 ) BE61X ( / 1 ) BE631 ( / 22 ) BE771 ( / 31 ) BE1121 ( / 12 ) BE1141 ( / 9 ) BE1251 ( / 4 ) BE1291 ( / 8 ) BE1641 ( / 5 ) EARS-Net susceptibility test results: Linezolid and ENCFAE in *A low number of samples (e.g. <1) means percentages should be interpreted with caution due to large Confidence Intervals. For the selection of Antibiotics behind each group see EARS-Net protocol Page 31 /

32 BE11 ( / 13 ) BE31 ( / 9 ) BE61 ( / 12 ) BE241 ( / 13 ) BE45X ( / 33 ) BE561 ( / 28 ) BE1 ( / 17 ) BE771 ( / 31 ) BE1121 ( / 13 ) BE1141 ( / 9 ) BE1251 ( / 4 ) BE1291 ( / 15 ) BE11 ( / 2 ) BE1641 ( / 5 ) BE631 ( 1 / 22 ) EARS-Net susceptibility test results: Teico and ENCFAE in *A low number of samples (e.g. <1) means percentages should be interpreted with caution due to large Confidence Intervals. For the selection of Antibiotics behind each group see EARS-Net protocol Page 32 /

33 BE11 ( / 13 ) BE31 ( / 9 ) BE61 ( / 12 ) BE71 ( / 3 ) BE171 ( / 15 ) BE241 ( / 13 ) BE371 ( / 4 ) BE441 ( / 11 ) BE45X ( / 33 ) BE48x ( / 3 ) BE561 ( / 28 ) BE1 ( / 17 ) BE61X ( / 29 ) BE74X ( / 12 ) BE751 ( / 11 ) BE771 ( / 31 ) BE971 ( / 36 ) BE1121 ( / 14 ) BE1141 ( / 9 ) BE1251 ( / 4 ) BE1291 ( / 15 ) BE11 ( / 2 ) BE1641 ( / 5 ) BE11 ( / 11 ) BE631 ( 1 / 22 ) EARS-Net susceptibility test results: Vanco and ENCFAE in *A low number of samples (e.g. <1) means percentages should be interpreted with caution due to large Confidence Intervals. For the selection of Antibiotics behind each group see EARS-Net protocol Page 33 /

34 BE241 ( / 1 ) BE61X ( 6 / 11 ) BE11 ( 2 / 3 ) BE31 ( 4 / 5 ) BE74X ( 8 / 1 ) BE751 ( 4 / 5 ) BE631 ( 9 / 11 ) BE11 ( 5 / 6 ) BE971 ( 35 / 42 ) BE1121 ( 5 / 6 ) BE61 ( 15 / 17 ) BE45X ( 16 / 18 ) BE1291 ( 8 / 9 ) BE1 ( 22 / 24 ) BE12 ( 1 / 1 ) BE171 ( 5 / 5 ) BE371 ( 2 / 2 ) BE48x ( 2 / 2 ) BE771 ( 3 / 3 ) BE1141 ( 4 / 4 ) BE1251 ( 2 / 2 ) BE11 ( 2 / 2 ) BE1641 ( 2 / 2 ) 7.6 E. faecium EARS-Net susceptibility test results: Aminopenicillins and ENCFAI in *A low number of samples (e.g. <1) means percentages should be interpreted with caution due to large Confidence Intervals. For the selection of Antibiotics behind each group see EARS-Net protocol Figure : E. faecium resistance percentage by lab to aminopenicillins grouping the antibiotics AMOXICILLIN, AMPICILLIN Page 34 /

35 BE371 ( / 2 ) BE771 ( / 4 ) BE1251 ( / 2 ) BE1291 ( / 9 ) BE1641 ( / 1 ) BE74X ( 1 / 9 ) BE1121 ( 1 / 6 ) BE31 ( 1 / 5 ) BE751 ( 1 / 5 ) BE1 ( 5 / 19 ) BE61 ( 7 / 17 ) BE45X ( 11 / 19 ) BE1141 ( 4 / 4 ) EARS-Net susceptibility test results: High-level genta and ENCFAI in *A low number of samples (e.g. <1) means percentages should be interpreted with caution due to large Confidence Intervals. For the selection of Antibiotics behind each group see EARS-Net protocol Page 35 /

36 BE11 ( / 6 ) BE12 ( / 1 ) BE31 ( / 5 ) BE61 ( / 9 ) BE171 ( / 4 ) BE241 ( / 1 ) BE371 ( / 2 ) BE441 ( / 2 ) BE45X ( / 18 ) BE1 ( / 5 ) BE61X ( / 1 ) BE631 ( / 11 ) BE74X ( / 1 ) BE751 ( / 1 ) BE771 ( / 4 ) BE1121 ( / 6 ) BE1141 ( / 4 ) BE1251 ( / 2 ) BE1291 ( / 5 ) BE1641 ( / 1 ) EARS-Net susceptibility test results: Linezolid and ENCFAI in *A low number of samples (e.g. <1) means percentages should be interpreted with caution due to large Confidence Intervals. For the selection of Antibiotics behind each group see EARS-Net protocol Page 36 /

37 BE11 ( / 6 ) BE12 ( / 1 ) BE61 ( / 17 ) BE241 ( / 1 ) BE45X ( / 19 ) BE631 ( / 11 ) BE771 ( / 4 ) BE1121 ( / 6 ) BE1141 ( / 4 ) BE1251 ( / 2 ) BE1291 ( / 9 ) BE11 ( / 2 ) BE1641 ( / 1 ) BE1 ( 1 / 23 ) BE31 ( 1 / 5 ) EARS-Net susceptibility test results: Teico and ENCFAI in *A low number of samples (e.g. <1) means percentages should be interpreted with caution due to large Confidence Intervals. For the selection of Antibiotics behind each group see EARS-Net protocol Page 37 /

38 BE11 ( / 6 ) BE12 ( / 1 ) BE61 ( / 17 ) BE171 ( / 5 ) BE241 ( / 1 ) BE371 ( / 2 ) BE441 ( / 2 ) BE45X ( / 19 ) BE48x ( / 2 ) BE61X ( / 11 ) BE631 ( / 11 ) BE751 ( / 5 ) BE771 ( / 4 ) BE1121 ( / 6 ) BE1141 ( / 4 ) BE1251 ( / 2 ) BE1291 ( / 9 ) BE11 ( / 2 ) BE1641 ( / 2 ) BE11 ( / 3 ) BE1 ( 1 / 24 ) BE971 ( 3 / 42 ) BE74X ( 1 / 1 ) BE31 ( 1 / 5 ) EARS-Net susceptibility test results: Vanco and ENCFAI in *A low number of samples (e.g. <1) means percentages should be interpreted with caution due to large Confidence Intervals. For the selection of Antibiotics behind each group see EARS-Net protocol Page 38 /

39 BE11 ( / 1 ) BE12 ( / 1 ) BE31 ( / 7 ) BE61 ( / 26 ) BE71 ( / 2 ) BE12 ( / 9 ) BE241 ( / 14 ) BE371 ( / 4 ) BE441 ( / 9 ) BE57x ( / 1 ) BE631 ( / 13 ) BE751 ( / 16 ) BE771 ( / 22 ) BE1141 ( / 5 ) BE1251 ( / 4 ) BE1641 ( / 2 ) BE1291 ( 1 / 22 ) BE74X ( 2 / 42 ) BE45X ( 3 / 16 ) BE48x ( 1 / 5 ) BE1 ( 4 / 2 ) BE971 ( 4 / 2 ) BE1121 ( 5 / 14 ) BE11 ( 1 / 2 ) P. aeruginosa EARS-Net susceptibility test results: Amikacin and PSEAER in *A low number of samples (e.g. <1) means percentages should be interpreted with caution due to large Confidence Intervals. For the selection of Antibiotics behind each group see EARS-Net protocol Page 39 /

40 BE12 ( / 1 ) BE61 ( / 26 ) BE71 ( / 2 ) BE12 ( / 9 ) BE371 ( / 4 ) BE631 ( / 13 ) BE751 ( / 15 ) BE771 ( / 22 ) BE1141 ( / 5 ) BE1251 ( / 4 ) BE11 ( / 8 ) BE1641 ( / 2 ) BE61X ( 1 / 22 ) BE241 ( 1 / 13 ) BE1291 ( 3 / 28 ) BE11 ( 1 / 8 ) BE31 ( 1 / 8 ) BE45X ( 2 / 16 ) BE74X ( 7 / 42 ) BE1121 ( 5 / 14 ) BE11 ( 1 / 2 ) EARS-Net susceptibility test results: Aminoglycosides and PSEAER in *A low number of samples (e.g. <1) means percentages should be interpreted with caution due to large Confidence Intervals. For the selection of Antibiotics behind each group see EARS-Net protocol Figure : P. aeruginosa resistance percentage by lab to aminoglycosides grouping the antibiotics GENTAMICIN, TOBRAMYCIN Page 4 /

41 BE12 ( / 1 ) BE31 ( / 7 ) BE71 ( / 2 ) BE12 ( / 9 ) BE241 ( / 14 ) BE371 ( / 4 ) BE441 ( / 9 ) BE57x ( / 1 ) BE631 ( / 13 ) BE771 ( / 22 ) BE1141 ( / 5 ) BE1251 ( / 4 ) BE11 ( / 8 ) BE1641 ( / 2 ) BE11 ( / 2 ) BE561 ( 1 / 27 ) BE61 ( 1 / 26 ) BE751 ( 1 / 16 ) BE61X ( 2 / 22 ) BE11 ( 1 / 1 ) BE1291 ( 3 / 23 ) BE74X ( 6 / 42 ) BE48x ( 1 / 5 ) BE971 ( 4 / 2 ) BE1121 ( 3 / 14 ) BE1 ( 6 / 2 ) BE45X ( 6 / 16 ) EARS-Net susceptibility test results: Carbapenems and PSEAER in *A low number of samples (e.g. <1) means percentages should be interpreted with caution due to large Confidence Intervals. For the selection of Antibiotics behind each group see EARS-Net protocol Figure : P. aeruginosa resistance percentage by lab to carbapenems grouping the antibiotics IMIPENEM, MEROPENEM Page 41 /

42 BE11 ( / 1 ) BE12 ( / 1 ) BE31 ( / 7 ) BE71 ( / 2 ) BE12 ( / 9 ) BE241 ( / 14 ) BE371 ( / 4 ) BE57x ( / 1 ) BE751 ( / 16 ) BE771 ( / 22 ) BE1121 ( / 14 ) BE1251 ( / 4 ) BE1291 ( / 22 ) BE1641 ( / 2 ) BE11 ( / 2 ) BE61 ( 1 / 26 ) BE61X ( 2 / 22 ) BE971 ( 2 / 2 ) BE441 ( 1 / 9 ) BE45X ( 2 / 16 ) BE11 ( 1 / 8 ) BE631 ( 2 / 13 ) BE74X ( 8 / 42 ) BE48x ( 1 / 5 ) BE1141 ( 1 / 5 ) BE1 ( 7 / 2 ) EARS-Net susceptibility test results: Ceftazidime and PSEAER in *A low number of samples (e.g. <1) means percentages should be interpreted with caution due to large Confidence Intervals. For the selection of Antibiotics behind each group see EARS-Net protocol Page 42 /

43 BE12 ( / 1 ) BE31 ( / 7 ) BE71 ( / 2 ) BE12 ( / 9 ) BE371 ( / 4 ) BE48x ( / 5 ) BE57x ( / 1 ) BE1141 ( / 5 ) BE1291 ( / 24 ) BE61 ( 1 / 26 ) BE771 ( 1 / 22 ) BE751 ( 1 / 18 ) BE45X ( 1 / 16 ) BE11 ( 1 / 1 ) BE61X ( 3 / 22 ) BE241 ( 2 / 14 ) BE631 ( 2 / 13 ) BE74X ( 8 / 41 ) BE441 ( 2 / 9 ) BE171 ( 3 / 13 ) BE1 ( 5 / 2 ) BE1251 ( 1 / 4 ) BE11 ( 2 / 8 ) BE1121 ( 4 / 14 ) BE1641 ( 1 / 2 ) BE11 ( 1 / 2 ) EARS-Net susceptibility test results: Fluoroquinolones and PSEAER in *A low number of samples (e.g. <1) means percentages should be interpreted with caution due to large Confidence Intervals. For the selection of Antibiotics behind each group see EARS-Net protocol Figure : E. coli resistance percentage by lab to fluoroquinolones grouping the antibiotics CIPROFLOXACIN, LEVOFLOXACIN Page 43 /

44 BE12 ( / 1 ) BE31 ( / 7 ) BE71 ( / 2 ) BE371 ( / 4 ) BE57x ( / 1 ) BE61X ( / 22 ) BE751 ( / 16 ) BE771 ( / 22 ) BE1121 ( / 14 ) BE1141 ( / 4 ) BE1251 ( / 4 ) BE11 ( / 8 ) BE1641 ( / 2 ) BE11 ( / 2 ) BE1291 ( 1 / 21 ) BE45X ( 1 / 16 ) BE241 ( 1 / 14 ) BE61 ( 2 / 26 ) BE11 ( 1 / 1 ) BE12 ( 1 / 9 ) BE441 ( 1 / 9 ) BE631 ( 2 / 13 ) BE74X ( 8 / 42 ) BE48x ( 2 / 5 ) BE1 ( 8 / 2 ) EARS-Net susceptibility test results: Piperacillin and PSEAER in *A low number of samples (e.g. <1) means percentages should be interpreted with caution due to large Confidence Intervals. For the selection of Antibiotics behind each group see EARS-Net protocol Figure : P. aeruginosa resistance percentage by lab to piperacillin (+tazobactam) grouping the antibiotics PIPERACILLIN, PIPERACILLIN/TAZOBACTAM Page 44 /

45 8. ACKNOWLEDGEMENTS We wish to thank all labs, including the national reference laboratoria, who have sent us their data and look forward to receiving your feedback on how to improve data collection and analyses to best fit your needs. In particular we wish to thank the reference lab for S. pneumoniae of University of Leuven (KULeuven -Prof. J. Verhaegen) which collected and provided the complete data collection for this germ. [Type text] Page 45 /

46 9.1 Antimicrobial codes Table 3 Explanation of official ECDC Antimicrobial codes 9. Annex Code Name Code Name Code Name ACM Acetylmidecamycin DIT Cefditoren OXA Oxacillin AMB Amphotericin B DKB Dibekacin OXO Oxolinic acid AMC Amoxicillin/Clavulanic acid DOX Doxycycline OXY Oxytetracycline AMK Amikacin ECO Econazole PAN Panipenem AMP Ampicillin ENR Enrofloxacin PAR Paromomycin AMR Amprolium ENX Enoxacin PAS P-Aminosalicylic acid AMX Amoxicillin EPE Eperozolid PEF Pefloxacin APL Apalcillin EPP Epiroprim PEN Penicillin G APR Apramycin ERY Erythromycin PIM Pentisomicin APX Aspoxicillin ETH Ethambutol PIP Piperacillin ARB Arbekacin ETI Ethionamide PIR Piromidic acid ASP Acetylspiramycin ETO Etopabat PIS Piperacillin/Sulbactam AST Astromicin ETP Ertapenem PKA Propikacin ATM Aztreonam FAR Faropenem PNO Penicillin/Novobiocin AVI Avilamycin FEP Cefepime PNV Penicillin V AVO Avoparcin FLA Flavomycin POL Polymixin B AXS Amoxicillin/Sulbactam FLC Flucloxacillin PPA Pipemidic acid AZL Azlocillin FLE Fleroxacin PRC Piridicillin AZM Azithromycin FLM Flumequine PRI Pristinamycin BAC Bacitracin FLO Flomoxef PRL Pirlimycin BAM Bacampicillin FLR Florfenicol PRM Primycin BCZ Bicozamycin FLU Fluconazole PRP Propicillin BDP Brodimoprim FMD Fosmidomycin PRX Premafloxacin BIA Biapenem FOS Fosfomycin PTH Prothionamide BUT Butoconazole FOX Cefoxitin PTZ Pentizidone CAC Cefacetrile FRM Framycetin PZA Pyrazinamide CAP Capreomycin FRZ Furazolidone QDA Quinupristin/Dalfopristin CAR Carumonam FUS Fusidic acid RAC Ractopamine CAT Cefetamet GAT Gatifloxacin RIB Rifabutin CAZ Ceftazidime GEH Gentamicin-High RID Cefaloridin CCL Cefetecol (Cefcatacol) GEM Gemifloxacin RIF Rifampin CCP Cefcapene GEN Gentamicin ROK Rokitamycin CCV Ceftazidime/Clavulanic acid GRI Griseofulvin ROS Rosoxacin CDR Cefdinir GRX Grepafloxacin RXT Roxithromicin CDZ Cefodizime HAB Habekacin SAL Salinomycin CEC Cefaclor HAP Cephapirin SAM Ampicillin/Sulbactam CED Cephradine HET Hetacillin SAR Sarafloxacin CEM Cefteram HYG Hygromycin SBC Sulbenicillin CEP Cephalothin INH Isoniazid SDI Sulfadiazine CFB Cefbuperazone IPM Imipenem SDM Sulfadimidine CFM Cefixime ISE Isepamicin SIS Sisomicin CFP Cefoperazone ISO Isoconazole SMX Sulfamethoxazole CFR Cefadroxil ITR Itraconazole SNA Sulfasuccinamide CFS Cefsulodin JOS Josamycin SOX Sulfisoxazole CFZ Cefpimizole KAH Kanamycin-High SPI Spiramycin CHE Cefotiam hexetil KAN Kanamycin SPT Spectinomycin CHL Chloramphenicol KET Ketoconazole SPX Sparfloxacin Kitasamycin (Leucomycin) SRX Sarmoxicillin CIC Ciclacillin KIT CID Cefonicid LAS Lasalocid SSS Sulfonamides CIN Cinoxacin LEX Cephalexin STH Streptomycin-High CIP Ciprofloxacin LIN Lincomycin STR Streptomycin CLA Clavulanic acid LNZ Linezolid SUC Sulconazole CLI Clindamycin LOM Lomefloxacin SUD Sulfadimethoxine CLO Cloxacillin LOR Loracarbef SUL Sulbactam CLR Clarithromycin LSP Linco-spectin SUM Sulfamethazine CLX Clinafloxacin LVX Levofloxacin SUP Sulfachlorpyridazine CMX Cefmenoxime MAN Cefamandole SUT Sulfathiazole CMZ Cefmetazole MCR Micromomicin SXT Trime- [Type text] Page 46 /

47 Code Name Code Name Code Name thoprim/sulfamethoxazole CND Ceforanide MCZ Miconazole SZO Sulfamazone Mecillinam (Amdinocillin) TAZ Tazobactam CNX Cefminox MEC COL Colistin MEL Meleumycin TBQ Tilbroquinol CPD Cefpodoxime MEM Meropenem TCC Ticarcillin/Clavulanic acid CPI Cefetamet pivoxil MES Mesulfamide TCY Tetracycline CPM Cefpiramide MET Methicillin TDC Tiodonium chloride CPO Cefpirome MEZ Mezlocillin TEC Teicoplanin CPR Cefprozil MFX Moxifloxacin TEM Temocillin CPX Cefpodoxime proxetil MID Midecamycin TET Tetroxoprim CRB Carbenicillin MIL Miloxacin TFX Tosufloxacin CRD Cefroxadine MNO Minocycline THA Thiacetazone CRO Ceftriaxone MON Monensin sodium THI Thiamphenicol CSL Cefoperazone/Sulbactam MOX Moxalactam (Latamoxef) TIA Tiamulin Mezlocillin/Sulbactam TIC Ticarcillin CSU Cefsumide MSU CTB Ceftibuten MTP Metioprim TIL Tilmicosin CTC Cefotaxime/Clavulanic acid MTR Metronidazole TIN Tinidazole CTE Chlortetracycline MUP Mupirocin TIO Ceftiofur CTF Cefotiam MXT Metioxate TLP Talmetoprim CTO Cetocycline NAF Nafcillin TLT Telithromycin CTR Clotrimazole NAL Nalidixic acid TMP Trimethoprim CTS Cefotaxime/Sulbactam NAR Narasin TMX Temafloxacin CTT Cefotetan NEO Neomycin TOB Tobramycin CTX Cefotaxime NET Netilmicin TRL Troleandomycin CTZ Cefatrizine NIC Nicarbazin TRO Trospectomycin CXA Cefuroxime axetil NIF Nifuroquine TVA Trovafloxacin CXM Cefuroxime sodium NIT Nitrofurantoin TXC Tioxacin CYC Cycloserine NIZ Nitrofurazone TYL Tylosin CZD Cefazedone NOR Norfloxacin TZP Piperacillin/Tazobactam CZL Cefetrizole NOV Novobiocin VAN Vancomycin CZO Cefazolin NTR Nitroxoline VIO Viomycin CZX Ceftizoxime NVA Norvancomycin VIR Virginiamycine DAP Daptomycin NYS Nystatin ZON Cefuzonam DEM Demeclocycline OFX Ofloxacin DFX Danofloxacin OLE Oleandomycin DIC Dicloxacillin OPT Optochin DIF Difloxacin ORN Ornidazole DIR Dirithromycin ORS Ormemetropim/Sulfameth oxine [Type text] Page 47 /

48 9.2 Background on resistance mechanisms S. aureus Relevance in AMR surveillance The oxacillin-resistant form (MRSA) has been the most important documented cause of antimicrobial-resistant healthcare-associated infections worldwide. MRSA infections are added to the number of infections caused by methicillin-susceptible S. aureus. A high incidence of MRSA therefore adds to the overall burden of infections caused by S. aureus in hospitals Resistance mechanisms Oxacillin-resistance Staphylococcus aureus acquires resistance to meticillin and all other beta-lactam antimicrobials through expression of an exogenous meca gene that codes for a penicillin-binding protein (PBP2a) with low affinity for beta-lactams. The level of meticillin resistance, as defined by the MIC depends on the amount of PBP2 production, which is influenced by various other genetic factors. Resistance levels of meca-positive strains can thus range from phenotypically susceptible to highly resistant. Rifampicin resistance For rifampicin, the mechanism of resistance is mutation in the rpob-gene, leading to production of RNA polymerase with low affinity for rifampicin and other rifamycins. Fluoroquinolone resistance Resistance to fluoroquinolones is mediated by the mutations in ParC or ParE (subunits of topoisomerase IV) and/or GyrA (subunit of DNA gyrase/topoisomerase IV). Additionally, resistance may be conferred by efflux S. pneumoniae Relevance in AMR surveillance S. pneumoniae is the most common cause of pneumonia worldwide. Morbidity and mortality are high, annually approximately 3 million people are estimated to die of pneumococcal infections. Interestingly, serotypes most frequently involved in pneumococcal disease or colonisation in infants are also most frequently associated with AMR. However, serotype replacement due to increased use of the pneumococcal conjugate vaccine (PCV) might change this over time Resistance mechanisms Penicillin resistance Alterations in PBPs result in reduced affinity to penicillins. The mutations can cause different degrees of resistance, from low-level clinical resistance conventionally termed intermediate to full clinical resistance. Intermediately resistant strains are less susceptible than susceptible strains but they are often successfully treated with high doses of benzyl-penicillin or aminopenicillins as long as meningitis is absent. MLS Macrolide, lincosamide and streptogramin (MLS) antimicrobials are chemically distinct, but all bind to a ribosomal subunit inhibiting the initiation of mrna binding and thus act as protein synthesis inhibitors. There are two predominant resistance mechanisms against MLS antimicrobials in S. pneumoniae: The acquisition of an erythromycin ribosomal methylation gene (erm) The acquisition of a macrolide efflux system gene (mef(e)) Fluoroquinolone (levofloxacin and moxifloxacin) Resistance to fluoroquinolones is mediated by the mutations in ParC and/or GyrA. Additionally, resistance may be conferred by efflux. [Type text] Page 48 /

49 9.2.3 E. coli Relevance in AMR surveillance E. coli is the most frequent cause of bacteraemia and urinary tract infections (both community- and hospitalacquired) Resistance mechanisms Bèta-lactams Resistance to beta-lactams is mostly due to production of plasmid coded beta-lactamases. Surveillance has therefore focused on aminopenicillins and third-gen cephalosporins. The first ESBLs in E. coli were variants of the TEM or SHV enzymes. During the past decade, however, these enzymes have largely been replaced by the CTX-M-type ESBLs, which are now the most common ESBLs in E. coli. An important new threat that will require close surveillance is the emergence of carbapenem resistance in E. coli, providing resistance to most or all available beta-lactam agents. Carbapenem resistance is mediated by metallo-betalactamases (such as the VIM, IMP or NDM enzyme) or serine-carbapenemases (such as the KPC enzymes). Fluoroquinolones Resistance to fluoroquinolones arises through stepwise mutations in the coding regions of the gyrase subunits (gyra and gyrb) and DNA topoisomerase IV (parc). Accumulation of mutations in several of these genes increases the MIC in a stepwise manner. Low-level resistance to fluoroquinolones may also arise from lower outer membrane permeability (changes in porins) or higher efflux (upregulation of efflux pumps). Aminoglycosides Resistance to aminoglycosides can be due to methylation of the large ribosomal subunit, or by production of enzymes that acetylate, adenylate or phosphorylate aminoglycoside molecules thereby neutralizing it. Among E. coli isolates resistant to third-generation cephalosporins, many labs test for the presence of an ESBL-enzyme but this data is not included in the 211 dataset. Combination (third-generation cephalosporins, fluoroquinolones, aminoglycosides) This leaves only a few therapeutic options, mostly carbapenems, colistin, tigecyclin, temocillin K. pneumoniae Relevance in AMR surveillance Klebsiella pneumoniae is associated with opportunistic infections in individuals with impaired immune systems, such as diabetic, alcoholic and hospitalised patients with indwelling devices. The most common sites of infection are the urinary tract and the respiratory tract. Klebsiella pneumoniae is the second most frequent cause of Gram-negative bloodstream infections after Escherichia coli Resistance mechanisms Resistance traits for K. pneumoniae are similar to the ones described in E. coli. An exception are the aminopenicillins since K. pneumoniae is intrinsically resistant to aminopenicillins due to a chromosomally encoded SHV beta-lactamase. Carbapenems have been widely used in many countries as an answer to the increasing rate of ESBL-producing Enterobacteriaceae. As a consequence there has been an emergence of resistance to carbapenems, especially in K. pneumoniae. The blaoxa-48 gene codes for an oxacillinase (OXA-48) that causes resistance to penicillin and reduces susceptibility to carbapenems, but not to expanded-spectrum cephalosporins. The level of resistance is often low and such strains are thus frequently missed in laboratories using automated AST systems. A combination of OXA-48-like enzymes with ESBLs such as CTX-M15 can occur in Klebsiella spp. and can result in a highly drug-resistant phenotype. [Type text] Page 49 /