Antibacterial Resistance In Wales

A Report from Public Health Wales Antimicrobial Resistance Programme Surveillance Unit: Antibacterial Resistance In Wales 2005-2013 Authors: Maggie Heginbothom and Robin Howe Version: 1 Antibacterial Resistance in Wales 2005-2013 Date: 18/11/2014 Page: 1 of 58 Status: Final Antimicrobial Resistance Programme: Surveillance Unit 1

Table of Contents Table of Contents... 2 Section 1: Introduction... 3 Section 2: Key points of interest... 4 Section 3: Methods... 5 Resistance data...5 Section 4: Monitoring Trends in Resistance... 9 UK 5 Year Antimicrobial Resistance Strategy... 9 Background...9 ARHAI Primary Data Set... 10 Section 5.1: Antimicrobial resistance rates for the most common organisms causing bacteraemia... 11 Background... 11 Escherichia coli... 12 Enterobacter spp., Serratia spp., Proteus spp., and Ps. Aeruginosa... 22 Enterobacter spp... 23 Serratia spp... 24 Proteus spp... 25 Pseudomonas aeruginosa... 26 Staphylococcus aureus... 27 Meticillin Sensitive Staphylococcus aureus... 30 Meticillin Resistant Staphylococcus aureus... 32 Enterococcus spp... 34 Streptococcus pneumoniae... 36 Section 5.2: Antimicrobial resistance rates for urinary coliforms... 38 Community Urinary Coliforms... 42 Out-patient Urinary Coliforms... 43 In-patient Urinary Coliforms... 44 Section 5.3: Antimicrobial resistance rates for Staphylococcus aureus... 45 MSSA... 47 MRSA... 49 Section 5.4: Antimicrobial resistance rates for other pathogens.... 50 Haemophilus influenzae... 52 Streptococcus pneumoniae... 54 Streptococcus pyogenes... 55 Campylobacter species... 56 Neisseria gonorrhoeae... 57 2

Section 1: Introduction Antimicrobial resistance is an increasing problem that can result in difficulty in treating infections, leading to failed therapy and potential complications. Treatment for most infections is started empirically before antimicrobial susceptibilities are known. A particular problem with the spread of antimicrobial resistance is that it becomes more difficult to select empirical therapy that will have reliable activity. The aim of this report from the Welsh Antimicrobial Resistance Programme Surveillance Unit is to provide data that can be used to design empirical therapy guidance, and to track antimicrobial resistance trends in Wales from 2005 to 2013. The report has had to be selective in what is presented, and concentrates on the major acute hospitals and district general hospitals in Wales, and the local community health boards. 3

Section 2: Key points of interest UK 5 Year Antimicrobial Resistance Strategy The Wales resistance trends for drug-bug combinations reported by ARHAI as part of the UK 5 year Antimicrobial Resistance Strategy are comparable to the aggregated rates and trends for the UK (page 10). However, in some cases there is considerable variability in resistance rates between different areas and hospitals. E. coli (the commonest cause of blood stream infections in Wales) Resistance to co-amoxiclav, fluoroquinolones and 3 rd generation cephalosporins remains high, but stable. Resistance to gentamicin and piperacillin-tazobactam appears to be increasing, with particularly high rates emerging in some hospitals. Carbapenem resistance has emerged in Wales Staphylococcus aureus Flucloxacillin resistance rates for Staphylococcus aureus bacteraemias were variable between hospitals and ranged from 3.3% in the University Hospital Llandough to 38.8% in Ysbyty Glan Clwyd (page 28). Tetracycline resistance There has been an increase in usage of tetracyclines across Wales in the last few years. This may be responsible for increasing resistance rate emerging in various organisms. Resistance in MRSA (meticillin resistant S. aureus from blood cultures and wound swabs has increased to 15-20% with rates of >50% in some areas. Resistance in Streptococcus pneumoniae has risen to 8.2% Urinary tract infections Coliforms (the commonest cause of urinary tract infections in Wales) Resistance to most antimicrobials has increased over the last 9 years (page 39): o Trimethoprim (first-line empirical therapy for uncomplicated UTI in the community) resistance has increased to 34.8%. This high rate of resistance reflects an element of selective testing. The true rate of resistance in patients presenting with uncomplicated UTI in the community is likely to be considerably lower, and trimethoprim remains the suggested first-line empirical therapy for these patients. o Co-amoxiclav resistance decreased from 17.2% in 2011 to 10.5% in 2013. o Ciprofloxacin resistance remained unchanged at 10%. o Nitrofurantoin resistance remained stable at approximately 12%. 4

Section 3: Methods Resistance data Data presented Antimicrobial resistance data is provided for the following selected areas and specific pathogens: Top ten bacteraemia pathogens Urinary coliforms (community & hospital) Wound swab isolates (community & hospital) o Staphylococcus aureus including MRSA from wound swabs All specimens (community & hospital) o Streptococcus pneumoniae o Streptococcus pyogenes o Haemophilus influenzae o Campylobacter spp. o Neisseria gonorrhoeae Community data is from samples referred from a general practice and hospital data is from samples submitted from hospital in-patients or out-patients as described. Data sources Antimicrobial susceptibility testing data was extracted from the regional DataStore systems. Data from Nevill Hall Hospital for 2005 & 2006 is not included in this report as it was not available for this period. Community data is presented by DataStore site e.g. data for specimens processed by the laboratories at Prince Philip and West Wales General hospitals will both be reported together as Carmarthen community data (J). The DataStore sites, and the codes and abbreviations for community and hospital data included in this report are shown in Table 1. Data interpretation As with all surveillance schemes, appropriate interpretation of the data, with an appreciation of the potential biases, is key. The main potential biases which should be considered in the data presented herein are: Sampling bias o This occurs if the submission of samples to the microbiology laboratory does not represent all patients presenting with that infection, but is selective in some way. If this is the case, the published resistance rate may be skewed, and not representative of the true rate in patients presenting with uncomplicated infection. This effect is likely to be more of an issue with certain sample types. For example bacteraemia data is felt to be fairly representative, since most patients presenting with sepsis will have a blood culture sent. However if general practitioners only submit urine samples from patients who have failed initial therapy, the published rates of resistance will be falsely high. 5

Selective testing o This occurs if a laboratory only tests susceptibility to a certain agent against selected organisms. For example, a laboratory might only test some agents when an organism is resistant to first-line drugs. This would result in falsely high published rates of resistance. In order to reduce the effect of selective testing on the published rates, data is only included if >80% of a given isolate from a given specimen is tested against the agent. Methodological variability o There are many methods available for antimicrobial susceptibility testing which may give inconsistent results. In order to reduce this effect on the published rates the Welsh Antimicrobial Chemotherapy Group is working to standardize testing across Wales. All but one laboratory use a combination of the BSAC (British Society for Antimicrobial Chemotherapy) standardized disc sensitivity method, and the BD Phoenix automated AST/ID system. Duplicate testing o This occurs if a patient has multiple specimens tested from a single infection episode. Potentially this can skew the resistance data. In order reduce the effect of this; duplicate isolates are removed from analysis by a sub-routine in DataStore. Isolates are deemed to be duplicates if the same organism with the same antibiogram is grown from the same sample type within 14 days (for hospital in-patients) or 91 days (for community patients). All Wales data The All-Wales resistance rates for each antimicrobial comprise an aggregate of data from a number of different laboratories. All-Wales resistance rates are only presented for organisms where no testing bias occurred at individual hospital level see below. Individual Hospital/Laboratory data Individual hospital or laboratory resistance rates are only presented for organisms where 80% of such isolates from the given sample type was tested and where the number of isolates tested exceeds 9. Duplicates Data from duplicate isolates was removed prior to analysis. For community data, organisms from the same patient, with the same identification and susceptibility pattern isolated 91 days from the date of the initial isolate were excluded, and for hospital data the cut-off was 14 days. Antimicrobial Groups Although there has been a move towards standardization of antimicrobials used for AST, some variation between laboratories remains (e.g. differences in choice and number of third generation cephalosporins tested). In such cases data is aggregated and resistance rates are expressed at group level. 6

Generally, most laboratories only test a single agent from antimicrobial groups such as fluoroquinolones and carbapenems where appropriate, but the choice of agent often varies between laboratories. The antimicrobial groups included in this report comprise of the following aggregated susceptibility data: Fluoroquinolones ciprofloxacin &/or levofloxacin, norfloxacin Third generation cephalosporins (3GC) ceftazidime &/or cefotaxime, ceftriaxone, cefpodoxime. Carbapenems imipenem &/or meropenem, ertapenem. Susceptibility results Throughout data is presented in tables and on graphs as resistance rates with 95% confidence intervals. 1 For the purpose of this report susceptibility results recorded as intermediate are included in the category resistant, and in the case of penicillin susceptibility results for S. pneumoniae results recorded as intermediate, low- level or high-level resistance are included in the category resistant. 1. Newcombe, Robert G. "Two-Sided Confidence Intervals for the Single Proportion: Comparison of Seven Methods," Statistics in Medicine, 17, 857-872 (1998). Other surveillance schemes This report focuses on comparisons of data collected for Wales in the calendar years 2005 and 2013. To provide some external context to the data presented, it has been also been compared to surveillance data from other sources see websites: Public Health England (PHE): http://www.hpa.org.uk/topics/infectiousdiseases/infectionsaz/antimicrobialr esistance/ British Society for Antimicorbial Chemotherapy (BSAC): http://www.bsac.org.uk/ European Centre for Disease Prevention and Control (EARS-Net): http://www.ecdc.europa.eu/en/healthtopics/antimicrobial_resistance/database /Pages/database.aspx All of the above surveillance schemes are also susceptible to potential biases, particularly selective coverage and selective reporting. Thus comparisons with the presented data should be treated with caution. NB. Throughout this document all resistance rates quoted from PHE publications relate to England, Wales and Northern Ireland (unless otherwise stated), and data quoted from EARS-Net website database relate to the United Kingdom (UK). 7

Table 1: Codes for hospital and community data Hospital Hospital Code DataStore Site Princess of Wales B Neath Port Talbot Singleton Morriston Nevill Hall Royal Gwent T S E M Swansea Newport Wrexham Maelor H Wrexham Ysbyty Gwynedd K Bangor Ysbyty Glan Clwyd L Rhyl University Hospital of Wales University Hospital Llandough D F Cardiff Prince Charles N Merthyr Royal Glamorgan C Pontypridd Glangwili Prince Philip P J Carmarthen Bronglais A Aberystwyth Withybush G Haverfordwest All-Wales R Z 8

Section 4: Monitoring Trends in Resistance UK 5 Year Antimicrobial Resistance Strategy Background In 2014, a sub-group of ARHAI was established to recommend surveillance outputs to support the UK Five Year Antimicrobial Resistance Strategy. Appendix C Monitoring Trends in Resistance of the Strategy document states: Changes in the level of resistance to antibiotics like the carbapenems, which are often the last option for hard to treat infections, will be monitored. The agreed drug-bug combinations for monitoring resistance are listed in Table 2; the combinations were ratified by the Department of Health (DoH) High-Level Steering Group. Public Health Wales provided the Wales data to ARHAI for this surveillance project. Blood specimens (except N. gonorrhoeae data) 14 day episode de-duplication Non-susceptible (NS) is resistant and intermediate isolate totals combined Where two antimicrobials from the same class are listed an or relationship is applied, the more resistant result takes priority Table 2: ARHAI Drug-Bug Combinations Specimen Organism Data Set Antimicrobial cefotaxime or ceftazidime imipenem or meropenem Primary Escherichia coli ciprofloxacin gentamicin Secondary piperacillin/tazobactam cefotaxime or ceftazidime imipenem or meropenem Primary Klebsiella pneumoniae ciprofloxacin gentamicin Secondary piperacillin/tazobactam Blood Culture cefotaxime or ceftazidime Klebsiella oxytoca Primary imipenem or meropenem ciprofloxacin gentamicin piperacillin/tazobactam Pseudomonas spp. Primary ceftazidime imipenem or meropenem Acinetobacter spp. Secondary colistin Enterococcus spp. Secondary vancomycin Staphylococcus aureus Secondary meticillin Streptococcus pneumoniae Primary penicillin All specimens ceftriaxone Neisseria gonorrhoeae Primary azithromycin 9

ARHAI Primary Data Set Table 3 shows the resistance rates for Wales compared with the UK aggregate rates for the primary data set drug-bug combinations. There are small differences in some of the resistance rates, but generally the trends in resistance are comparable. Table 3: ARHAI Primary Data Set ARHAI Primary data set Escherichia coli 2009 2010 2011 2012 2013 Cefotaxime &/or ceftazidime Wales 14 14 13 16 13 *UK 11 10 11 11 10 Ciprofloxacin Wales 22 22 21 23 20 *UK 20 19 19 19 18 Gentamicin Wales 6 9 9 10 11 *UK 8 9 9 10 10 Imipenem &/or meropenem Wales 0.1 *UK 0.1 0.1 0.1 0.1 Klebsiella pneumoniae 2009 2010 2011 2012 2013 Cefotaxime &/or ceftazidime Wales 14 10 8 9 10 *UK 11 11 10 11 11 Ciprofloxacin Wales 12 10 8 9 10 *UK 10 10 9 10 11 Gentamicin Wales 7 7 4 3 3 *UK 7 7 7 7 8 Imipenem &/or meropenem Wales 0.4 0.7 0.3 0.6 *UK 0.3 0.6 0.8 0.7 0.8 Pseudomonas spp. 2009 2010 2011 2012 2013 Ceftazidime Wales 8 12 8 6 6 *UK 8 8 8 7 7 Imipenem &/or meropenem Wales 10 13 10 11 4 *UK 12 10 11 10 9 Streptococcus pneumoniae 2009 2010 2011 2012 2013 Penicillin Wales 2 2 3 2 5 *UK 2 3 3 3 3 *UK rates include data for England, Scotland, Wales and Northern Ireland provided by ARHAI sub-group. The secondary data set has not been published by ARHAI as yet, and cannot be presented in this report. 10

Section 5.1: Antimicrobial resistance rates for the most common organisms causing bacteraemia Background The 2013 top ten bacteraemia report for Wales comprises the commonest organisms isolated from blood cultures in Wales, see Table 4 below. Internet: http://www.wales.nhs.uk/sites3/page.cfm?orgid=379&pid=13066#z Intranet: http://howis.wales.nhs.uk/sites3/page.cfm?orgid=379&pid=18707#topt Table 4: Top Ten Bacteraemias Rank Organism Rate per 100,000 bed days 1 Escherichia coli (E. coli) 74 2 Staphylococcus aureus (MSSA) 25 3 Enterococcus species 16 4 Klebsiella species 16 5 Streptococcus pneumoniae 9 6 Coagulase-negative Staphylococcus 8 7 Pseudomonas aeruginosa 6 8 Proteus species 6 9 Staphylococcus aureus (MRSA) 5 10 Enterobacter species 5 The datasets include infections originating from community and hospital sources (inpatient and out-patient), and so may be affected by local clonal strains which can result in marked variability in resistance rates between hospitals/regions; results should be interpreted with caution. Since coagulase negative staphylococci are frequently contaminants when isolated from blood cultures, data on susceptibility are not presented here. However, although Serratia species have dropped out of the top 10, resistance data for the genus will be presented as it has appeared in previous reports. The data in this report is not presented in rank order, but rather an order to allow easy comparison of resistances for related bacteria. 11

Escherichia coli (n=2135 in 2013) E. coli is the commonest organism grown from blood cultures in Wales and the UK. The All-Wales patterns of resistance for 2005 to 2013 are shown in Figure 1, and the individual hospital resistance rates for ARHAI primary drug set are shown in Table 5.The data for 2013 shows a statistically significant decrease in resistance to coamoxiclav compared with the 2012 rates. Imipenem and meropenem resistance rates remain below 1% in the UK. 50 45 40 35 Resistance (%) 30 25 20 15 10 5 0 2005 2013 2012 3GC COA CARB CXM FQ GEN PTZ Figure 1: All-Wales resistance rates for E. coli bacteraemia (2005 to 2013). 12

Table 5: Escherichia coli Escherichia coli from blood cultures Resistance rates including (95% Confidence Intervals) Duplicate Cut Off: 14 days Time period: 1 January - 31 December 2013 Location Code (Number) COA PTZ GEN PTZ+GEN A (n=54) 37.3 (25.3, 51.0) 6.3 (2.1, 16.8) 8.3 (3.3, 19.6) (, 7.4) B (n=126) 19.8 (13.8, 27.7) 6.4 (3.3, 12.1) 7.9 (4.4, 14.0) 2.4 (0.8, 6.8) C (n=125) 5 (41.4, 58.6) 5.7 (2.8, 11.4) 10.3 (6.1, 16.9) 0.8 (0.1, 4.5) D (n=208) 36.5 (30.3, 43.3) 9.8 (6.4, 14.6) 10.6 (7.1, 15.5) 2.4 (1.0, 5.6) E (n=84) 34.5 (25.2, 45.2) 10.7 (5.7, 19.1) 8.3 (4.1, 16.2) 2.4 (0.7, 8.3) F (n=258) 45.3 (39.3, 51.6) 8.1 (5.3, 12.2) 9.3 (6.3, 13.6) 2.0 (0.9, 4.7) G (n=90) 22.2 (14.9, 31.8) 7.0 (3.2, 14.4) 5.6 (2.4, 12.4) 1.2 (0.2, 6.3) H (n=191) 20.7 (15.6, 27.1) 27.5 (21.6, 34.3) 15.5 (11.0, 21.4) J (n=148) 23.8 (17.5, 31.4) 2.2 (0.7, 6.2) 2.8 (1.1, 7.1) (, 2.7) K (n=126) 38.4 (30.3, 47.2) 14.3 (9.2, 21.5) 2 (13.9, 27.9) 8.8 (5.0, 15.1) L (n=156) 45.8 (38.2, 53.7) 4.5 (2.2, 9.0) 14.7 (1, 21.2) 1.9 (0.7, 5.5) M (n=121) 36.1 (28.1, 45.1) 5.9 (2.9, 11.6) N (n=104) 44.8 (35.6, 54.3) 8.0 (4.1, 15.0) P (n=63) 39.7 (28.5, 52.0) 12.7 (6.6, 23.1) 4.8 (1.6, 13.1) 1.6 (0.3, 8.5) Q (n=12) 18.2 (5.1, 47.7) (, 25.9) (, 25.9) (, 25.9) R (n=53) 32.1 (21.1, 45.5) 8.0 (3.2, 18.8) 5.7 (1.9, 15.4) (, 7.1) S (n=195) 30.9 (24.8, 37.7) 3.6 (1.8, 7.3) 6.7 (3.9, 11.1) 0.5 (0.1, 2.9) T (n=15) 4 (19.8, 64.3) 13.3 (3.7, 37.9) 13.3 (3.7, 37.9) 13.3 (3.7, 37.9) All-Wales: Resistance rates 36.5 (34.3, 38.6) 8.5 (7.4, 9.8) 10.7 (9.5, 12.1) 3.4 (2.7, 4.2) All-Wales: Number of isolates 1925 2025 2101 2018 Location Code (Number) AMO 3GC AMI FQ A (n=54) 18.0 (9.8, 30.8) 2.2 (0.4, 11.3) 27.1 (16.6, 41.0) B (n=126) 61.1 (52.4, 69.2) 13.5 (8.6, 20.5) 17.7 (12.0, 25.4) C (n=125) 66.1 (57.3, 73.9) 2 (13.9, 27.9) 3.4 (1.3, 8.4) 20.6 (14.5, 28.5) D (n=208) 61.0 (54.2, 67.4) 12.0 (8.3, 17.1) 1.5 (0.5, 4.2) 18.8 (14.0, 24.6) E (n=84) 65.5 (54.8, 74.8) 14.3 (8.4, 23.3) 19.0 (12.1, 28.7) F (n=258) 63.2 (57.0, 68.9) 10.9 (7.6, 15.4) 1.2 (0.4, 3.5) 20.7 (16.1, 26.2) G (n=90) 61.8 (51.4, 71.2) 5.6 (2.4, 12.4) 1.2 (0.2, 6.4) 15.6 (9.5, 24.4) H (n=191) 68.9 (62.0, 75.1) 41.6 (34.8, 48.7) J (n=148) 12.2 (7.8, 18.4) 9.9 (6.0, 16.0) K (n=126) 64.3 (55.6, 72.1) 24.8 (18.1, 33.0) 1.6 (0.4, 5.6) 24.0 (17.4, 32.2) L (n=156) 54.2 (46.3, 61.8) 17.3 (12.2, 24.0) (, 2.4) 25.0 (18.9, 32.3) M (n=121) 57.5 (48.6, 66.0) 11.7 (7.1, 18.6) 1.7 (0.5, 6.0) 15.0 (9.7, 22.5) N (n=104) 56.4 (46.7, 65.7) 11.4 (6.7, 18.9) 13.3 (8.1, 21.1) P (n=63) 58.7 (46.4, 7) 12.7 (6.6, 23.1) 4.8 (1.6, 13.1) 20.6 (12.5, 32.2) Q (n=12) 54.5 (28.0, 78.7) (, 25.9) (, 25.9) (, 27.8) R (n=53) 66.7 (52.5, 78.3) 3.8 (1.0, 12.8) (, 7.4) 11.3 (5.3, 22.6) S (n=195) 62.1 (55.1, 68.6) 11.3 (7.6, 16.5) 15.0 (10.7, 20.7) T (n=15) 6 (35.7, 80.2) 6.7 (1.2, 29.8) 13.3 (3.7, 37.9) All-Wales: Resistance rates 62.1 (59.9, 64.2) 13.3 (11.9, 14.9) 1.6 (1.1, 2.3) 20.4 (18.7, 22.2) All-Wales: Number of isolates 2038 1943 1635 2103 Location Code (Number) ERT IMI MER IMI or MER A (n=54) (, 7.9) (, 7.4) (, 7.4) B (n=126) (, 3.0) (, 3.0) C (n=125) (, 3.2) (, 3.2) (, 3.0) (, 3.0) D (n=208) (, 1.8) (, 1.9) (, 1.8) (, 1.8) E (n=84) (, 5.3) (, 4.4) (, 4.4) (, 4.4) F (n=258) 0.4 (0.1, 2.3) (, 1.5) 0.4 (0.1, 2.3) G (n=90) (, 4.3) 1.2 (0.2, 6.3) H (n=191) J (n=148) (, 2.7) (, 2.7) K (n=126) (, 3.3) (, 3.0) L (n=156) (, 2.4) (, 2.4) (, 2.4) M (n=121) 0.9 (0.2, 4.7) (, 3.4) (, 3.1) (, 3.1) N (n=104) (, 4.0) (, 3.6) P (n=63) (, 5.7) (, 5.7) (, 5.7) Q (n=12) (, 29.9) (, 25.9) (, 25.9) (, 25.9) R (n=53) (, 7.4) (, 6.8) (, 6.8) S (n=195) (, 2.4) (, 1.9) (, 1.9) (, 1.9) T (n=15) (, 20.4) (, 20.4) (, 20.4) All-Wales: Resistance rates 0.2 (0.1, 0.7) 0.1 (, 0.4) (, 0.2) 0.1 (, 0.4) All-Wales: Number of isolates 1224 1632 1778 1976 Key: COA = co-amoxiclav, PTZ = piperacillin/tazobactam, GEN = gentamicin, PTZ/GEN = combined resistance to both agents, AMO = amoxicillin, 3GC = resistance to ceftazidime &/or cefotaxime, cefpodoxime, ceftriaxone, AMI = amikacin, FQ = resistance to ciprofloxacin &/or levofloxacin, ERT = ertapenem, IMI = imipenem, MER = meropenem, IMI or MER = resistance to either or both agents Note: The range of resistance is outlined with boxes e.g. the range for co-amoxiclav (COA) was 16.7% to 49.6%; individual hospital resistance rates statistically higher than the All-Wales rate are highlighted in blue. Resistance rates are not recorded when <80% of the isolates were tested (All-Wales rate shown in red). The resistance rates for E. coli bacteraemia in Wrexham Maelor (H) and Ysbyty Gwynedd (K) were notably high to a number of agents suggesting a higher incidence of multi-resistant strains locally. Imipenem and/or meropenem resistant E. coli were reported in UHW and Withybush. 13

ARHAI Primary data Set Interpretation Tables 6-10: The tables show trends in resistance to drug/bug combinations in the ARHAI primary data set at hospital level, across time. The tables use a colour gradation based on the lowest resistance to the highest resistance figures, to highlight local patterns of resistance across time. The first column in the tables show the hospital code and the median number of isolates tested across the time period e.g. in Table 6, hospital code A (43) denotes Bronglais hospital with a median number of 43 isolates tested per year across the five year period. Note: Individual hospital or laboratory resistance rates are only presented for organisms where 80% of such isolates from the given sample type was tested and where the number of isolates tested exceeds 9. It is important to remember when interpreting this data set that hospital level data often represents small numbers of organisms, and single isolate resistance within these numbers can produce misleadingly large changes in resistance. Table 6: Trends in third generation cephalosporin resistance for E. coli by hospital (2009-2013) Key: A= Bronglais B = Princess of Wales C = Royal Glamorgan D = Royal Gwent E = Morriston F = UHW G = Withybush H = Wrexham Maelor J = Glangwili K = Ysbyty Gwynedd L = Ysbyty Glan Clwyd M = Nevill Hall N = Prince Charles P = UHL Q = Velindre R = Prince Philip S = Singleton T = Neath Port Talbot 14

Table 7: Trends in fluoroquinolone resistance for E. coli by hospital (2009-2013) Table 8: Trends in gentamicin resistance for E. coli by hospital (2009-2013) Key: A= Bronglais B = Princess of Wales C = Royal Glamorgan D = Royal Gwent E = Morriston F = UHW G = Withybush H = Wrexham Maelor J = Glangwili K = Ysbyty Gwynedd L = Ysbyty Glan Clwyd M = Nevill Hall N = Prince Charles P = UHL Q = Velindre R = Prince Philip S = Singleton T = Neath Port Talbot 15

Table 9: Trends in piperacillin/tazobactam resistance for E. coli (2009-2013) Table 10: Trends in imipenem/meropenem resistance for E. coli (2009-2013) Key: A= Bronglais B = Princess of Wales C = Royal Glamorgan D = Royal Gwent E = Morriston F = UHW G = Withybush J = Glangwili K = Ysbyty Gwynedd L = Ysbyty Glan Clwyd M = Nevill Hall N = Prince Charles P = UHL Q = Velindre R = Prince Philip S = Singleton T = Neath Port Talbot 16

Klebsiella spp. (n=474 in 2013) The All-Wales patterns of antimicrobial resistance in Klebsiella spp. are shown in Figure 2 and Table 11; with no significant difference in resistance rates between 2012 and 2013. Imipenem and meropenem resistance rates remain below 1% in the UK. Resistance (%) 34 32 30 28 26 24 22 20 18 16 14 12 10 8 6 4 2 0 2006 2005 3GC COA CARB CXM FQ GEN PTZ Figure 2: All-Wales antimicrobial resistance rates for Klebsiella species; isolated from blood culture (2005 to 2013) 2013 17

Table 11: Klebsiella spp. Klebsiella spp. from blood cultures Resistance rates including (95% Confidence Intervals) Duplicate Cut Off: 14 days Time period: 1 January - 31 December 2013 Location Code (Number) COA PTZ GEN PTZ+GEN A (n=11) 54.5 (28.0, 78.7) 18.2 (5.1, 47.7) 9.1 (1.6, 37.7) 9.1 (1.6, 37.7) B (n=29) 20.7 (9.8, 38.4) 10.7 (3.7, 27.2) 17.2 (7.6, 34.5) 10.7 (3.7, 27.2) C (n=22) 9.1 (2.5, 27.8) 4.5 (0.8, 21.8) (, 14.9) (, 14.9) D (n=43) 11.6 (5.1, 24.5) 4.8 (1.3, 15.8) 2.3 (0.4, 12.1) (, 8.4) E (n=34) 14.7 (6.4, 30.1) 11.8 (4.7, 26.6) (, 10.2) (, 10.2) F (n=67) 16.4 (9.4, 27.1) 9.0 (4.2, 18.2) 4.5 (1.5, 12.4) 4.5 (1.5, 12.4) G (n=17) 5.9 (1.0, 27.0) 6.3 (1.1, 28.3) 11.8 (3.3, 34.3) (, 19.4) H (n=32) 21.9 (11.0, 38.8) (, 10.7) (, 10.7) J (n=29) 3.4 (0.6, 17.2) (, 12.1) (, 11.7) (, 12.1) K (n=32) 28.1 (15.6, 45.4) 15.6 (6.9, 31.8) 6.3 (1.7, 20.1) 3.1 (0.6, 15.7) L (n=42) 23.8 (13.5, 38.5) 2.4 (0.4, 12.3) 7.1 (2.5, 19.0) (, 8.4) M (n=23) 26.1 (12.5, 46.5) 5.3 (0.9, 24.6) 4.5 (0.8, 21.8) (, 16.8) N (n=23) 8.7 (2.4, 26.8) (, 15.5) (, 22.8) P (n=13) 7.7 (1.4, 33.3) 7.7 (1.4, 33.3) (, 22.8) (, 22.8) R (n=12) 8.3 (1.5, 35.4) (, 24.3) (, 25.9) (, 25.9) S (n=35) 20.6 (10.3, 36.8) 15.2 (6.7, 30.9) 5.7 (1.6, 18.6) 3.0 (0.5, 15.3) All-Wales: Resistance rates 16.7 (13.5, 20.4) 8.6 (6.4, 11.6) 4.3 (2.8, 6.5) 2 (1.1, 3.8) All-Wales: Number of isolates 438 452 466 449 Location Code (Number) AMO 3GC AMI FQ A (n=11) _ 18.2 (5.1, 47.7) (, 25.9) 9.1 (1.6, 37.7) B (n=29) _ 17.2 (7.6, 34.5) 21.4 (10.2, 39.5) C (n=22) _ 4.5 (0.8, 21.8) (, 14.9) (, 14.9) D (n=43) _ 4.7 (1.3, 15.5) (, 8.2) (, 8.2) E (n=34) _ 8.8 (3.0, 23.0) (, 14.3) (, 10.2) F (n=67) _ 10.4 (5.2, 2) (, 5.4) 9.0 (4.2, 18.2) G (n=17) _ 5.9 (1.0, 27.0) (, 19.4) (, 18.4) H (n=32) _ 12.5 (5.0, 28.1) J (n=29) _ (, 11.7) (, 13.3) (, 11.7) K (n=32) _ 18.8 (8.9, 35.3) (, 10.7) 15.6 (6.9, 31.8) L (n=42) _ 11.9 (5.2, 25.0) (, 8.6) 16.7 (8.3, 30.6) M (n=23) _ (, 14.3) (, 15.5) (, 14.3) N (n=23) _ 4.3 (0.8, 21.0) 8.7 (2.4, 26.8) P (n=13) _ (, 22.8) (, 22.8) (, 22.8) R (n=12) _ (, 24.3) (, 25.9) S (n=35) _ 5.7 (1.6, 18.6) 14.7 (6.4, 30.1) All-Wales: Resistance rates 62.0 (59.9, 64.1) 8.2 (6.0, 11.1) 0.3 (, 1.5) 7.7 (5.6, 10.5) All-Wales: Number of isolates 2048 439 363 467 Location Code (Number) ERT IMI MER IMI or MER A (n=11) 9.1 (1.6, 37.7) (, 25.9) 9.1 (1.6, 37.7) B (n=29) (, 12.1) (, 12.1) C (n=22) (, 14.9) (, 14.9) (, 14.9) (, 14.9) D (n=43) (, 8.4) (, 8.4) (, 8.2) (, 8.2) E (n=34) (, 11.7) (, 10.2) (, 10.2) (, 10.2) F (n=67) (, 5.4) 1.5 (0.3, 8.0) 1.5 (0.3, 8.0) G (n=17) (, 19.4) (, 19.4) H (n=32) J (n=29) (, 13.3) (, 12.1) (, 11.7) K (n=32) (, 11.4) (, 10.7) L (n=42) 2.4 (0.4, 12.3) (, 8.4) (, 8.4) M (n=23) (, 16.8) (, 16.8) (, 14.9) (, 14.9) N (n=23) (, 16.8) (, 17.6) (, 14.9) P (n=13) (, 22.8) (, 22.8) (, 22.8) R (n=12) (, 25.9) (, 25.9) S (n=35) 2.9 (0.5, 14.9) 2.9 (0.5, 14.9) 2.9 (0.5, 14.9) All-Wales: Resistance rates 0.7 (0.2, 2.7) 0.5 (0.1, 1.9) 0.5 (0.1, 1.9) 0.7 (0.2, 2.0) All-Wales: Number of isolates 270 373 388 440 Key: COA= co-amoxiclav, PTZ = piperacillin/tazobactam, GEN = gentamicin, PTZ/GEN = combined resistance to both agents, AMO = amoxicillin, 3GC = resistance to ceftazidime &/or cefotaxime, cefpodoxime, ceftriaxone, AMI = amikacin, FQ = resistance to ciprofloxacin &/or levofloxacin, ERT = ertapenem, IMI = imipenem, MER = meropenem, IMI or MER = resistance to either or both agents Note: The resistance rates for Klebsiella spp. bacteraemia at hospital level were not statistically different to the All-Wales rates except for co-amoxiclav resistance in Bronglais and gentamicin resistance in Princess of Wales (B). Imipenem and/or meropenem resistant Klebsiella spp. were reported in Bronglais (A), UHW (F) and Singleton (S). Resistance rates are not recorded if the organisms are intrinsically resistant to an antibacterial agent e.g. for amoxicillin, or when <80% of the isolates were tested (All-Wales rate shown in red). 18

ARHAI Primary data Set Interpretation Tables 12-16: The tables show trends in resistance to drug/bug combinations in the ARHAI primary data set at hospital level, across time. The tables use a colour gradation based on the lowest resistance to the highest resistance figures, to highlight local patterns of resistance across time. Note 1: The data is different to that shown in Table 3 (page 11); Table 3 shows the rates for Klebsiella pneumoniae as per ARHAI instructions, but the following tables show the data for all Klebsiella species to allow comparisons with previous reports. Note 2: Individual hospital or laboratory resistance rates are only presented for organisms where 80% of such isolates from the given sample type was tested and where the number of isolates tested exceeds 9. It is important to remember when interpreting this data set that hospital level data often represents small numbers of organisms, and single isolate resistance within these numbers can produce misleadingly large changes in resistance. Table 12: Trends in third generation cephalosporin resistance for Klebsiella spp. (2009-2013) Key: A= Bronglais B = Princess of Wales C = Royal Glamorgan D = Royal Gwent E = Morriston F = UHW G = Withybush H = Wrexham Maelor J = Glangwili K = Ysbyty Gwynedd L = Ysbyty Glan Clwyd M = Nevill Hall N = Prince Charles P = UHL R = Prince Philip S = Singleton 19

Table 13: Trends in fluoroquinolone resistance for Klebsiella spp. (2009-2013) Table 14: Trends in gentamicin resistance for Klebsiella spp. (2009-2013) Key: A= Bronglais B = Princess of Wales C = Royal Glamorgan D = Royal Gwent E = Morriston F = UHW G = Withybush H = Wrexham Maelor J = Glangwili K = Ysbyty Gwynedd L = Ysbyty Glan Clwyd M = Nevill Hall N = Prince Charles P = UHL R = Prince Philip S = Singleton 20

Table 15: Trends in piperacillin/tazobactam resistance for Klebsiella spp. (2009-2013) Table 16: Trends in imipenem/meropenem resistance for Klebsiella spp. (2009-2013) Key: A= Bronglais B = Princess of Wales C = Royal Glamorgan D = Royal Gwent E = Morriston F = UHW G = Withybush H = Wrexham Maelor J = Glangwili K = Ysbyty Gwynedd L = Ysbyty Glan Clwyd M = Nevill Hall N = Prince Charles P = UHL R = Prince Philip S = Singleton 21

Enterobacter spp., Serratia spp., Proteus spp., and Ps. Aeruginosa Table 17: Enterobacter spp., Serratia spp., Proteus spp., and Ps. aeruginosa Enterobacter spp., Serratia spp., Proteus spp., and Pseudomonas aeruginosa from blood cultures Resistance rates including (95% Confidence Intervals) Duplicate Cut Off: 14 days Time period: 1 January - 31 December 2013 Oragnism COA PTZ GEN PTZ+GEN Enterobacter spp. _ 13.9 (9.2, 20.5) 8.1 (4.7, 13.5) 2.1 (0.7, 5.9) All-Wales: Number of isolates 144 149 144 Serratia spp. _ 9.8 (5.2, 17.6) (, 3.9) (, 4.0) All-Wales: Number of isolates 92 94 92 Proteus spp. 17.6 (12.4, 24.5) 1.3 (0.4, 4.5) 15.3 (10.6, 21.7) 0.6 (0.1, 3.5) All-Wales: Number of isolates 153.0 157 163 157 * Pseudomonas aeruginosa _ 4.9 (2.5, 9.4) 3.0 (1.3, 6.9) 1.3 (0.3, 4.5) All-Wales: Number of isolates 163 169 159 Location Code (Number) AMO 3GC AMI FQ Enterobacter spp. _ 28.0 (21.3, 35.8) (, 3.1) 3.4 (1.5, 7.7) All-Wales: Number of isolates 143 121 147 Serratia spp. _ 29.3 21.0, 39.3) 1.4 (0.2, 7.4) 21.1 (14.1, 30.3) All-Wales: Number of isolates 92 73 95 Proteus spp. _ 3.9 (1.8, 8.3) 2.5 (0.9, 7.1) 10.6 (6.7, 16.4) All-Wales: Number of isolates 153 120 160 * Pseudomonas aeruginosa _ 5.6 (3.0, 10.3) 2.7 (0.9, 7.6) 5.3 (2.8, 9.8) All-Wales: Number of isolates 160 111 169 Location Code (Number) ERT IMI MER IMI or MER Enterobacter spp. 7.1 (3.5, 14.0) 1.6 (0.4, 5.7) 0.8 (0.1, 4.2) 1.4 (0.4, 5.0) All-Wales: Number of isolates 98 124 132 141 Serratia spp. 2.0 (0.4, 10.5) (, 4.9) (, 4.4) (, 4.0) All-Wales: Number of isolates 50 73 84 92 Proteus spp. 1.2 (0.2, 6.7) 6.8 (3.5, 12.8) (, 7.4) 5.2 (2.7, 1) All-Wales: Number of isolates 81 118 135 153 * Pseudomonas aeruginosa _ 3.0 (1.2, 7.4) 1.3 (0.4, 4.7) 2.4 (0.9, 6.0) All-Wales: Number of isolates 134 151 168 Key: COA = co-amoxiclav, PTZ = piperacillin/tazobactam, GEN = gentamicin, PTZ/GEN = combined resistance to both agents, AMO = amoxicillin, 3GC = resistance to ceftazidime &/or cefotaxime, cefpodoxime, ceftriaxone, AMI = amikacin, FQ = resistance to ciprofloxacin &/or levofloxacin, ERT = ertapenem, IMI = imipenem, MER = meropenem, IMI or MER = resistance to either or both agents Note: The numbers shown in red denote that <80% of total isolates were tested against the particular antibacterial agent. Resistance rates are not recorded if the organisms are intrinsically resistant to an antibacterial agent e.g. for amoxicillin. When <80% of all isolates were tested, the All-Wales rate is shown in red. 22

Enterobacter spp. (n=154 in 2013) The All-Wales patterns of antimicrobial resistance for Enterobacter spp. are shown in Figure 3 & Table 17. There has been a significant decrease in fluoroquinolone resistance across time, and in piperacillin/tazobactam resistance between 2010 and 2013. Resistance (%) 65 60 55 50 45 40 35 30 25 20 15 10 5 0 Figure 3: All-Wales antimicrobial resistance rates for Enterobacter species; isolated from blood culture (2005 to 2013) The resistance rates for piperacillin/tazobactam resistance are generally lower in the Wales data than the PHE data e.g. in 2012 the Wales rate was 9% compared with a UK rate of 20%. Although the rates of carbapenem resistance in Wales are higher than those reported by the PHE, the Wales figure includes ertapenem resistance data, and not only imipenem and meropenem data. Table 18: PHE data for Enterobacter species bacteraemia 2005-2012 Enterobacter spp. 2005 2006 2007 2008 2009 2010 2011 2012 Total reports: 2,522 2,613 2,675 2,414 2,208 2,037 2,052 1,917 Piperacillin/ Tazobactam Imipenem/ Meropenem Cefotaxime Ceftazidime Ciprofloxacin Gentamicin 2005 2013 3GC CARB FQ GEN PTZ % NS 23% 24% 21% 18% 17% 18% 16% 20% No. reports 1,368 1,594 1,884 1,774 1,554 1,484 1,582 1,499 % NS 1% 1.2% 1.1% 0.7% 0.4% <1% <1% <1% No. reports 1,506 1,732 1,984 1,909 1,662 1,524 1,561 1,486 % NS 40% 42% 37% 38% 35% 33% 29% 26% No. reports 1,040 1,213 1,271 1,195 1,081 993 1,012 999 % NS 42% 41% 36% 36% 32% 32% 30% 29% No. reports 1,334 1,519 1,769 1,612 1,376 1,370 1,391 1,317 % NS 15% 14% 10% 8% 6% 5% 5% 5% No. reports 1,860 2,092 2,237 1,987 1,693 1,638 1,683 1,6585 % NS 12% 11% 9% 7% 7% 5% 6% 6% No. reports 1,988 2,108 2,337 2,139 1,844 1,723 1,803 1,708 Key: % NS = percentage of non-susceptible isolates 23

Serratia spp. (n=97 in 2013) The All-Wales patterns of antimicrobial resistance for Serratia spp. are shown in Figure 4 and Table 17. There has been a statistically significant decrease in resistance rates third generation cephalosporins (3GC), fluoroquinolones (FQ) and piperacillin/tazobactam (PTZ) between 2005 and 2013. 75 70 65 60 55 Resistance (%) 50 45 40 35 30 25 20 15 2005 5 2013 10 0 3GC CARB FQ GEN PTZ Figure 4: All-Wales antimicrobial resistance rates for Serratia species; isolated from blood culture (2005 to 2013) The significant decrease in resistance between 2008 and 2012 reported by PHE is reflected in the Welsh data. Although the rates of carbapenem resistance in Wales are generally higher than those reported by the PHE, the Wales figure includes ertapenem resistance data, and not only imipenem and meropenem data. Table 19: PHE data for Serratia species bacteraemia 2005-2012 Serratia spp. Total reports: 2005 1,158 2006 1,270 2007 1,208 2008 1,071 2009 992 2010 943 2011 887 2012 827 Piperacillin/ Tazobactam % NS 20% 20% 16% 16% 12% 15% 10% 8% No. reports 604 774 828 764 712 712 707 657 Imipenem/ Meropenem % NS 0% 1% 0.3% 0.6% 0.1% 0.5% 0.4% <1% No. reports 642 807 888 821 780 735 701 675 % NS 27% 29% 28% 28% 30% 29% 21% 19% No. reports 426 548 582 537 541 497 458 454 % NS 18% 16% 14% 22% 20% 21% 16% 14% No. reports 549 681 742 678 647 681 643 620 % NS 26% 25% 20% 16% 12% 12% 11% 9% No. reports 854 996 1,007 864 800 794 756 709 % NS 2% 2% 1% 3% 3% 2% 1% 1% No. reports 1,002 1,002 1.046 917 855 838 824 762 Cefotaxime Ceftazidime Ciprofloxacin Gentamicin Key: % NS = percentage of non-susceptible isolates 24

Proteus spp. (n=166 in 2013) The All-Wales patterns of antimicrobial resistance in Proteus spp. are shown in Figure 5 & Table 17, with a statistically significant decrease in carbapenem and gentamicin resistance between 2012 and 2013 Note: Due to known issues with susceptibility testing of carbapenems with automated systems the reliability of the high carbapenem resistance is uncertain. 55 50 45 40 Resistance (%) 35 30 25 20 15 2005 5 0 3GC 2013 10 AMO COA CARB CXM FQ GEN PTZ Figure 5: All-Wales antimicrobial resistance rates for Proteus species; isolated from blood culture (2005 to 2013) The PHE data for Proteus spp., Morganella morganii & Providencia spp. bacteraemia shows that 89% of bacteraemias from this group were Proteus mirabilis and 4% were Proteus vulgaris. The PHE resistance rates for Proteus mirabilis 2006-2012 are shown for comparison with the Welsh data (see Figure 5 and Table 20). Table 20: PHE data for Proteus mirabilis bacteraemia 2006-2012 Proteus mirabilis Total reports: Amoxicillin Cefuroxime Cefotaxime Ceftazidime Ciprofloxacin Gentamicin Imipenem 2006 2007 2008 2009 2010 2011 2012 1,671 1,842 2,083 2,133 2,091 2,091 2,238 % NS 35% 30% 31% 32% 33% 34% 34% No. reports 1,289 1,459 1,719 1,660 1,690 1,793 1,909 % NS 5% 2% 2% 1% 2% 2% 1% No. reports 1,234 1,369 1,476 1,323 1,311 1,458 1,477 % NS 5% 1% 1% 0% 1% 2% 2% No. reports 743 858 983 1,044 1,005 1,0734 1,160 % NS 2% 1% 1% 1% 1% 2% 2% No. reports 916 1,190 1,355 1,380 1,383 1,517 1,512 % NS 7% 7% 6% 6% 6% 7% 9% No. reports 1,293 1,460 1,648 1,622 1,677 1,775 1,857 % NS 4% 4% 3% 6% 7% 7% 10% No. reports 1,296 1,527 1,816 1,779 1,795 1,897 2,000 % NS 1% 2% 4% 6% 8% 9% 5% No. reports 389 529 591 524 407 339 247 Key: % NS = percentage of non-susceptible isolates 25

Pseudomonas aeruginosa (n=173 in 2013) The All-Wales patterns of antimicrobial resistance in Pseudomonas aeruginosa are shown in Figure 6 & Table 17. The data is different to that shown in Table 3 (page 11); Table 3 shows the rates for Pseudomonas spp as per ARHAI instructions, but the following tables show the data for Ps. aeruginosa to allow comparisons with previous reports. 35 30 Resistance (%) 25 20 15 10 2013 0 2005 5 CARB CAZ CIP GEN PTZ Figure 6: All-Wales antimicrobial resistance rates for Pseudomonas aeruginosa; isolated from blood culture (2005 to 2013) There was a statistically significant decrease in ciprofloxacin resistance between 2011 and 2013. The PHE rates are shown below for comparison with the Welsh data (see Figure 6 and Table 21). http://www.hpa.org.uk/topics/infectiousdiseases/infectionsaz/bacteraemia/ Table 21: PHE data for Pseudomonas aeruginosa bacteraemia 2005-2012 Pseudomonas aeruginosa Total reports: 2006 2,866 2007 3,090 2008 3,987 2009 3,927 2010 3,833 2011 3,694 2012 3,743 Piperacillin/ Tazobactam % NS 4% 5% 6% 8% 7% 7% 9% No. reports 1,985 2,324 2,490 2,509 2,570 2,544 2,654 Imipenem % NS 11% 12% 9% 13% 12% 14% 13% No. reports 965 1,147 1,110 1,172 1,038 926 926 % NS 10% 9% 10% 11% 9% 9% 9% No. reports 1,087 1,396 1,713 1,785 2,017 2,210 2,3 % NS 7% 8% 7% 8% 8% 8% 6% No. reports 2,213 2,514 2,484 2,461 2,530 2,526 2,595 % NS 12% 12% 11% 11% 10% 11% 9% No. reports 2,393 2,646 2,657 2,709 2,696 2,703 2,728 % NS 5% 5% 4% 4% 5% 6% 4% No. reports 2,415 2,754 2,785 2,778 2,812 2,810 2,864 Meropenem Ceftazidime Ciprofloxacin Gentamicin Key: % NS = percentage of non-susceptible isolates 26

Staphylococcus aureus The All-Wales resistance rates for Staphylococcus aureus at hospital level are shown in Table 22, the data includes all Staphylococcus aureus both MSSA and MRSA. In 2013, flucloxacillin resistance rates for S. aureus bacteraemias in Ysbyty Glan Clwyd and Ysbyty Gwynedd were notably high; 38.8% and 32.7% respectively. Flucloxacillin resistance reflects the proportion of S. aureus bacteraemias that were MRSA; the proportions of MRSA bacteraemias were notably higher in these localities than other acute hospitals in Wales. Surveillance data was obtained from the Welsh Healthcare Associated Programme (WHAIP). Figure 7 shows the numbers of Staphylococcus aureus bacteraemias from 2005 to 2013. Across time both the number of Staphylococcus aureus (SAUR) and Meticillin Resistant Staphylococcus aureus (MRSA) bacteraemias has decreased, whilst the numbers of Meticillin Sensitive Staphylococcus aureus (MSSA) bacteraemias increased significantly between 2011 and 2013. 1200 1039 1000 Number of bacteraemias 923 800 759 632 600 407 400 200 0 164 2005 2006 2007 2008 2009 2010 2011 2012 2013 MRSA 407 341 363 344 286 229 203 180 164 MSSA 632 682 658 638 681 664 661 701 759 SAUR 1039 1023 1021 982 967 893 864 881 923 Figure 7: All-Wales Staphylococcus aureus bacteraemia numbers (2005 to 2013) 27

Table 22: Staphylococcus aureus (MSSA & MRSA) Staphylococcus aureus from blood cultures (MSSA & MRSA) Resistance rates including (95% Confidence Intervals) Duplicate Cut Off: 14 days Time period: 1 January - 31 December 2013 Location Code CLI A (n=13) (5.1, 47.7) 18.2 B (n=51) (0.3, 10.3) 2.0 C (n=56) (2.2, 17.5) 6.5 D (n=85) (8.4, 23.3) 14.3 E (n=65) F (n=162) 16.4 (11.2, 23.4) G (n=46) (3.4, 20.3) 8.7 H (n=56) 17.9 (1, 29.8) J (n=50) 28.0 (17.5, 41.7) K (n=49) (0.7, 18.3) 3.7 L (n=49) M (n=35) (4.8, 27.3) 12.1 N (n=40) P (n=30) (3.7, 27.2) 10.7 R (n=21) (7.7, 4) 19.0 S (n=71) 12.8 (10.6, 15.5) All-Wales: Resistance rates 710 All-Wales: Number of isolates Location Code FUS A (n=13) B (n=51) 29.4 (18.7, 43.0) C (n=56) 23.6 (14.4, 36.3) D (n=85) 27.2 (18.7, 37.7) E (n=65) 27.7 (18.3, 39.6) F (n=162) 27.0 (20.7, 34.4) G (n=46) (6.6, 27.3) 14.0 H (n=56) J (n=50) 28.6 (17.2, 43.6) K (n=49) 21.2 (10.7, 37.8) L (n=49) 44.9 (31.9, 58.7) M (n=35) (6.7, 30.9) 15.2 N (n=40) (8.3, 33.5) 17.6 P (n=30) (7.6, 34.5) 17.2 R (n=21) 26.3 (11.8, 48.8) S (n=71) 32.9 (23.0, 44.5) 25.8 (23.0, 28.9) All-Wales: Resistance rates 824 All-Wales: Number of isolates Location Code MUP A (n=13) B (n=51) (, 7.0) C (n=56) (, 6.9) D (n=85) (2.0, 12.2) 5.0 E (n=65) (0.3, 8.5) 1.6 F (n=162) (0.1, 3.5) 0.6 G (n=46) (, 7.7) H (n=56) J (n=50) K (n=49) L (n=49) (0.4, 10.7) 2.0 M (n=35) (0.6, 15.7) 3.1 N (n=40) P (n=30) (1.9, 22.0) 6.9 R (n=21) S (n=71) (, 5.7) (0.9, 2.9) 1.7 All-Wales: Resistance rates 725 All-Wales: Number of isolates ERY 18.2 7.8 12.5 6.0 10.8 15.6 14.3 7.7 12.5 (5.1, 47.7) (3.1, 18.5) (6.2, 23.6) (2.6, 13.2) (5.3, 20.6) (10.8, 22.0) (6.7, 27.8) (3.0, 18.2) (5.9, 24.7) 11.8 12.8 17.2 4.8 8.6 11.5 838 GEN (4.7, 26.6) (5.6, 26.7) (7.6, 34.5) (0.8, 22.7) (4.0, 17.5) (9.5, 13.8) 3.7 6.1 1.5 6.9 2.4 (1.0, 12.5) (2.6, 13.5) (0.3, 8.2) (3.9, 12.0) (0.4, 12.6) 6.1 6.1 8.8 10.8 6.9 2.8 5.5 786 RIF (, 8.4) (2.1, 16.5) (2.1, 16.5) (3.0, 23.0) (4.3, 24.7) (1.9, 22.0) (, 16.8) (0.8, 9.7) (4.1, 7.3) (, 7.0) (, 6.8) 1.3 FLU 23.1 11.8 12.5 21.2 12.3 16.0 10.9 25.0 26.0 32.7 38.8 5.7 1 3.3 14.3 14.1 17.7 701 LZD (8.2, 50.3) (5.5, 23.4) (6.2, 23.6) (13.8, 31.0) (6.4, 22.5) (11.2, 22.5) (4.7, 23.0) (15.5, 37.7) (15.9, 39.6) (21.2, 46.6) (26.4, 52.8) (1.6, 18.6) (4.0, 23.1) (0.6, 16.7) (5.0, 34.6) (7.8, 24.0) (15.3, 20.4) 1.6 2.5 (, 7.4) (, 6.9) (, 4.5) (0.3, 8.5) (1.0, 6.3) 2.4 (, 6.4) (0.4, 12.3) 3.4 3.1 1.2 753 TET (, 10.7) (, 10.7) (0.6, 17.2) (, 16.8) (0.8, 10.5) (0.6, 2.3) (, 5.7) (0.3, 4.5) (, 8.2) 3.6 6.3 3.2 7.5 4.3 (, 7.4) (1.0, 12.3) (2.7, 14.0) (0.9, 10.9) (4.4, 12.7) (1.2, 14.5) 2.1 (, 8.4) (0.4, 11.1) (, 7.3) 6.1 12.2 8.2 (1.7, 19.6) (5.7, 24.2) (3.2, 19.2) 0.4 724 (, 9.6) (, 11.7) (, 16.8) (, 5.7) (0.1, 1.2) 2.6 6.9 (0.5, 13.5) (1.9, 22.0) 2.8 5.9 797 (0.8, 9.7) (4.5, 7.8) Key:CLI = clindamycin, ERY = erythromycin, FUS = fusidic acid, GEN = gentamicin, LZD = linezolid, MUP = mupirocin, PEN = pencillin, RIF = rifampicin, TET = tetracycline. 28

ARHAI Primary data Set Interpretation Table 23: The table show trends in resistance to a drug/bug combination in the ARHAI primary data set at hospital level, across time. The tables use a colour gradation based on the lowest resistance to the highest resistance figures, to highlight local patterns of resistance across time. Table 23: Trends in meticillin resistance for Staphylococcus aureus (2009-2013) Key: A= Bronglais B = Princess of Wales C = Royal Glamorgan D = Royal Gwent E = Morriston F = UHW G = Withybush H = Wrexham Maelor J = Glangwili K = Ysbyty Gwynedd L = Ysbyty Glan Clwyd M = Nevill Hall N = Prince Charles P = UHL R = Prince Philip S = Singleton 29

Meticillin Sensitive Staphylococcus aureus (n=734 in 2013) The All-Wales pattern of antimicrobial resistance in MSSA is shown in Figure 8 and Table 24; with no statistically significant changes between 2005 and 2013. 20 18 16 Resistance (%) 14 12 10 8 6 ERY FUS GEN MUP 2013 0 2005 2005 2 2013 4 RIF TET Figure 8: All-Wales antimicrobial resistance rates for Meticillin Sensitive Staphylococcus aureus (MSSA) isolated from blood culture (2005 to 2013) The All-Wales antimicrobial resistance rates for MSSA are largely comparable to those published by BSAC for the UK except for clindamycin resistance which appears higher in Wales. In 2013, the All-Wales clindamycin resistance rate was 6.7% compared with the UK rate of 1.1%. The All-Wales rate is skewed by high local rates in some areas including Glangwili (16.2%), Bronglais (11.1%) and Nevill Hall hospitals (9.7%). This presumably reflects the varying presence of epidemic strains. In 2013, the All-Wales resistance rate for penicillin was 84.6%, and resistance to linezolid and vancomycin remained undetected. 30

Table 24: Meticillin Sensitive Staphylococcus aureus Meticillin Sensitive Staphylococcus aureus from blood cultures Resistance rates including (95% Confidence Intervals) Duplicate Cut Off: 14 days Time period: 1 January - 31 December 2013 Location Code CLI A (n=10) (2.0, 43.5) 11.1 B (n=45) (, 7.9) C (n=48) (1.3, 15.1) 4.5 D (n=67) (0.8, 10.4) 3.0 E (n=57) (3.9, 22.5) 9.8 F (n=136) (4.6, 14.7) 8.3 G (n=41) (2.5, 19.4) 7.3 H (n=42) (2.5, 19.0) 7.1 J (n=37) (7.7, 31.1) 16.2 K (n=33) L (n=30) M (n=33) (3.3, 24.9) 9.7 N (n=36) P (n=29) (2.1, 23.4) 7.4 R (n=18) (1.0, 25.8) 5.6 S (n=61) (4.9, 9.0) 6.7 All-Wales: Resistance rates 599 All-Wales: Number of isolates Location Code GEN A (n=10) B (n=45) C (n=48) (1.2, 14.2) 4.3 D (n=67) (2.5, 15.0) 6.3 E (n=57) (0.3, 9.3) 1.8 F (n=136) (0.8, 6.4) 2.3 G (n=41) (, 9.4) H (n=42) J (n=37) (, 11.4) K (n=33) (0.5, 15.3) 3.0 L (n=30) (, 11.4) M (n=33) (3.2, 24.2) 9.4 N (n=36) (3.1, 23.6) 9.1 P (n=29) (0.6, 17.7) 3.6 R (n=18) (, 19.4) S (n=61) (, 5.9) (1.9, 4.7) 3 All-Wales: Resistance rates 631 All-Wales: Number of isolates Location Code PEN A (n=10) 88.9 (56.5, 98.0) B (n=45) 77.8 (63.7, 87.5) C (n=48) 91.3 (79.7, 96.6) D (n=67) 86.7 (75.8, 93.1) E (n=57) 83.9 (72.2, 91.3) F (n=136) G (n=41) 75.6 (60.7, 86.2) H (n=42) J (n=37) K (n=33) 81.8 (65.6, 91.4) L (n=30) M (n=33) 81.3 (64.7, 91.1) N (n=36) 8 (64.1, 9) P (n=29) 10 (86.2, 100) R (n=18) S (n=61) 88.3 (77.8, 94.2) 87.6 (84.7, 9) All-Wales: Resistance rates 597 All-Wales: Number of isolates ERY 2 8.9 14.3 7.6 12.3 18.7 14.6 10.5 16.2 9.1 16.7 12.5 13.9 17.9 5.6 9.8 13.2 725 LZD (5.7, 51.0) (3.5, 20.7) (7.1, 26.7) (3.3, 16.5) (6.1, 23.2) (13.0, 26.1) (6.9, 28.4) (4.2, 24.1) (7.7, 31.1) (3.1, 23.6) (7.3, 33.6) (5.0, 28.1) (6.1, 28.7) (7.9, 35.6) (1.0, 25.8) (4.6, 19.8) (11.0, 15.9) (, 7.9) (, 7.9) (, 5.7) (, 6.5) (, 2.8) (, 8.4) (, 11.4) 0 603 RIF (, 11.4) (, 11.7) (, 12.1) (, 19.4) (, 6.5) (, 0.6) (, 7.9) (, 7.7) FUS 2 14.6 7.9 17.5 16.5 7.5 12.5 6.7 21.2 1 9.7 1 17.9 12.5 23.0 14.6 701 MUP (10.9, 33.8) (7.2, 27.2) (3.4, 17.3) (9.8, 29.4) (11.2, 23.8) (2.6, 19.9) (5.5, 26.1) (1.8, 21.3) (10.7, 37.8) (3.5, 25.6) (3.3, 24.9) (3.5, 25.6) (7.9, 35.6) (3.5, 36.0) (14.2, 34.9) (12.1, 17.4) 1.6 0.8 (, 7.9) (, 7.9) (0.3, 8.6) (, 6.5) (0.1, 4.1) (, 8.6) 3.3 3.3 (0.6, 16.7) (0.6, 16.7) 7.1 (2.0, 22.6) 1.4 592 TET (, 6.6) (0.7, 2.6) (, 6.5) (, 2.8) (, 9.0) 4.2 6.5 1.8 4.5 (, 8.4) (1.2, 14.0) (2.5, 15.4) (0.3, 9.4) (2.1, 9.5) (, 8.6) 3.2 (, 11.4) (0.6, 16.2) (, 11.4) 9.1 3.3 (3.1, 23.6) (0.6, 16.7) 0.2 605 (, 10.7) (, 12.1) (, 19.4) (, 6.5) (, 0.9) 2.9 3.6 (0.5, 14.9) (0.6, 17.7) 3.3 3.7 649 (0.9, 11.2) (2.5, 5.4) Key:CLI = clindamycin, ERY = erythromycin, FUS = fusidic acid, GEN = gentamicin, LZD = linezolid, MUP = mupirocin, PEN = pencillin, RIF = rifampicin, TET = tetracycline. 31

Meticillin Resistant Staphylococcus aureus (n=158 in 2013) The All-Wales pattern of antimicrobial resistance in MRSA is shown in Figure 9 & Table 25; with a statistically increase in tetracycline resistance between 2005 and 2013. 100 90 80 Resistance (%) 70 60 50 40 30 ERY 2007 0 2013 10 2005 20 FUS GEN MUP RIF TET Figure 9: All-Wales antimicrobial resistance rates for Meticillin Resistant Staphylococcus aureus (MRSA) isolated from blood culture (2005 to 2013) The All-Wales antimicrobial resistance rates for MRSA for 2005 to 2012 are largely comparable to those published by BSAC for the UK. BSAC have not as yet published antimicrobial resistance rates for MRSA for 2013, however the clindamycin resistance rates for Wales in 2013 were notably high at 45.9% compared with the BSAC rate of 13.1% in 2012. Resistance to vancomycin and linezolid has remained undetected. 32

Table 25: Meticillin Resistant Staphylococcus aureus Meticillin Resistant Staphylococcus aureus from blood cultures Resistance rates including (95% Confidence Intervals) Duplicate Cut Off: 14 days Time period: 1 January - 31 December 2013 Location Code CLI D (n=18) 55.6 (33.7, 75.4) F (n=27) 65.0 (43.3, 81.9) H (n=14) 5 (26.8, 73.2) J (n=13) 61.5 (35.5, 82.3) K (n=16) L (n=19) S (n=10) 45.9 (37.0, 55.2) All-Wales: Resistance rates 111 All-Wales: Number of isolates Location Code FUS D (n=18) (1.0, 25.8) 5.6 F (n=27) 30.8 (16.5, 5) H (n=14) (7.6, 47.6) 21.4 J (n=13) (, 24.3) K (n=16) (3.5, 36.0) 12.5 L (n=19) (5.5, 37.6) 15.8 S (n=10) (5.7, 51.0) 2 15.5 (10.6, 22.0) All-Wales: Resistance rates 155 All-Wales: Number of isolates Location Code MUP D (n=18) (5.8, 39.2) 16.7 F (n=27) (, 12.9) H (n=14) (, 22.8) J (n=13) K (n=16) L (n=19) (, 16.8) S (n=10) (, 29.9) (1.2, 7.5) 3.0 All-Wales: Resistance rates 133 All-Wales: Number of isolates ERY 55.6 73.1 5 61.5 87.5 89.5 7 70.1 157 GEN 3.8 8.3 2 3.3 150 RIF (33.7, 75.4) (53.9, 86.3) (26.8, 73.2) (35.5, 82.3) (64.0, 96.5) (68.6, 97.1) (39.7, 89.2) (62.5, 76.7) 7.7 1.4 139 (2.1, 24.1) (, 22.8) (, 24.3) (, 19.4) (, 16.8) (, 29.9) (0.4, 5.1) (, 17.6) (0.7, 18.9) (, 21.5) (1.5, 35.4) (, 19.4) (, 16.8) (5.7, 51.0) (1.4, 7.6) FQ 94.4 80.8 (74.2, 99.0) (62.1, 91.5) 83.3 (55.2, 95.3) 100 100 90.2 123 LZD (83.2, 100) (70.1, 100) (83.7, 94.3) 0 113 TET 5.9 23.1 28.6 18.8 15.8 15.5 148 (, 17.6) (, 12.9) (, 21.5) (, 29.9) (, 3.3) (1.0, 27.0) (11.0, 42.1) (11.7, 54.6) (6.6, 43.0) (5.5, 37.6) (, 27.8) (10.6, 22.2) Key:CLI = clindamycin, ERY = erythromycin, FUS = fusidic acid, GEN = gentamicin, LZD = linezolid, MUP = mupirocin, PEN = pencillin, RIF = rifampicin, TET = tetracycline. The number of MRSA bacteraemias has reduced markedly over the past few years and so the number of individual hospitals with 10 isolates or more has reduced, and so the table is small. When <80% of all isolates were tested, the All-Wales rate is shown in red. 33