Antibacterial Resistance In Wales

A Report from Public Health Wales Antimicrobial Resistance Programme Surveillance Unit: Antibacterial Resistance In Wales 2005-2012 Authors: Maggie Heginbothom Robin Howe & Catherine Thomas Version: 1 Antibacterial Resistance in Wales 2005-2012 Date: 18/11/2013 Page: 1 of 52 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... 6 Resistance data...6 Section 4.1: Antimicrobial resistance rates for the most common organisms causing bacteraemia... 10 Background... 10 Escherichia coli... 12 Klebsiella spp.... 15 Enterobacter spp... 18 Serratia spp.... 19 Proteus spp.... 20 Pseudomonas aeruginosa... 21 Staphylococcus aureus bacteraemias... 22 Meticillin Sensitive Staphylococcus aureus... 24 Meticillin Resistant Staphylococcus aureus... 26 Enterococcus spp... 28 Streptococcus pneumoniae... 30 Section 4.2: Antimicrobial resistance rates for urinary coliforms... 31 Community Urinary Coliforms... 35 Out-patient Urinary Coliforms... 36 In-patient Urinary Coliforms... 37 Section 4.3: Antimicrobial resistance rates for Staphylococcus aureus... 38 MSSA... 41 MRSA... 44 Section 4.4: Antimicrobial resistance rates for other pathogens.... 45 Haemophilus influenzae... 47 Streptococcus pneumoniae... 49 Streptococcus pyogenes... 50 Campylobacter species... 51 Neisseria gonorrhoeae... 52 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 2012. 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 Antimicrobial resistance in Wales has increased over the last 8 years for some of the major pathogens. In some cases there is considerable variability in resistance rates between different areas and hospitals. Blood stream infections E. coli (the commonest cause of blood stream infections in Wales) Resistance to most antimicrobials has increased in the last year (page 13): o Co-amoxiclav resistance increased to 42% o Ciprofloxacin resistance increased to 23% o 3rd generation cephalosporin resistance increased to 15% o Gentamicin resistance increased to 10% Public Health England recently issued the following alert A few E. coli samples (and rather more Klebsiella pneumoniae) with acquired carbapenemases are now being received by the PHE reference lab. UK microbiologists should be aware of these (many of the E. coli have an enzyme called New Delhi Metallo β-lactamase-1 (NDM- 1), which is epidemiologically often linked to India and Pakistan. Carbapenemases including Klebsiella Pneumoniae Carbapenemase (KPC) and Verona Imipenemase (VIM) are also circulating, with KPC dominant in K. pneumoniae, especially in North West England). In Wales, carbapenemase-producing E. coli and Klebsiellae remain extremely rare, with only a handful of isolates identified each year. Staphylococcus aureus Flucloxacillin resistance rates for Staphylococcus aureus bacteraemias were variable between hospitals and ranged from 5.6% in Prince Philip hospital to 38% in Ysbyty Gwynedd (page 22). Pseudomonas aeruginosa (a cause of healthcare-associated infections) Resistance in blood stream isolates to carbapenems remains high but has levelled off at 21% in 2012 (page 21). This is predominantly caused by porinloss and efflux mechanisms, although occasional carbapenemase producers have been identified. Urinary tract infections Coliforms (the commonest cause of urinary tract infections in Wales) Resistance to most antimicrobials has increased over the last 8 years (page 35): o Trimethoprim (first-line empirical therapy for uncomplicated UTI in the community) resistance has increased to 34%. 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. 4

o Co-amoxiclav resistance decreased from 17.2% in 2011 to 12.3% in 2012. This decrease is probably a laboratory artefact due to a change in methodology in some laboratories in 2012 (changing from BSAC systemic criteria for testing urine isolates to the BSAC UTI criteria). o Ciprofloxacin resistance remained unchanged at 10%. o Nitrofurantoin resistance remained stable at approximately 11%. Wound infections Staphylococcus aureus (from wound swabs) Resistance to fusidic acid, gentamicin, mupirocin and tetracycline, in Meticillin-resistant Staphylococcus aureus (MRSA) increased in 2012 (see pages 41 & 42). o As previously reported fusidic acid and tetracycline resistance remain prevalent in North Wales. o Whilst in Swansea, combined gentamicin and mupirocin resistance is notably high; 57% of gentamicin-resistant isolates in Swansea were also resistant to mupirocin. o Colleagues may wish to review the use of these agents with respect to potential therapeutic failure, and/or selection of resistance. Resistance rates for Meticillin-sensitive staphylococcus aureus (MSSA) have remained relatively stable. 5

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. 6

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 10. 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. 7

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, ertapnem. Susceptibility results Throughout data is presented in tables and on graphs as resistance rates with 95% confidence intervals (95% CI). 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 2012. To provide some external context to the data presented, it has been also been compared to surveillance data from other sources: Public Health England (PHE) Website: https://www.gov.uk/government/organisations/public-health-england British Society for Antimicorbial Chemotherapy (BSAC) Website: http://www.bsac.org.uk/ European Centre for Disease Prevention and Control (EARS-Net) Interactive database: http://ecdc.europa.eu/en/activities/surveillance/ears- Net/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). 8

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 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 9

Section 4.1: Antimicrobial resistance rates for the most common organisms causing bacteraemia Background The 2012 top ten bacteraemia report for Wales comprises the commonest organisms isolated from blood cultures in Wales, see Table 2 below. http://howis.wales.nhs.uk/sites3/page.cfm?orgid=379&pid=18707#topt Table 2: Top Ten Bacteraemias Rank Organism Rate per 100,000 bed days 1 Escherichia coli (E. coli) 59 2 Staphylococcus aureus (MSSA) 19 3 Enterococcus species 13 4 Klebsiella species 12 5 Streptococcus pneumoniae 9 6 Coagulase-negative Staphylococcus 7 =7 Staphylococcus aureus (MRSA) 6 =7 Pseudomonas aeruginosa 6 9 Proteus species 5 10 Enterobacter species 4 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. 10

Table 3: Escherichia coli TABLE 3: Escherichia coli from blood cultures Resistance rates including (95% Confidence Intervals) Duplicate Cut Off: 14 days Time period: 1 January - 31 December 2012 Location Code (Number) AMO (95% CI) COA (95% CI) PTZ (95% CI) CXM (95% CI) 3GC (95% CI) CARB (95% CI) FQ (95% CI) 3GC/FQ (95% CI) GEN (95% CI) A (n=65) 61.4 (48.4, 72.9) 33.3 (22.9, 45.6) 3.3 (0.9, 11.2) 13.8 (7.2, 24.9) 11.5 (5.7, 21.8) 0.0 (0.0, 5.9) 13.1 (6.8, 23.8) 8.2 (3.6, 17.8) 4.9 (1.7, 13.5) B (n=126) 63.7 (55.0, 71.6) 36.3 (28.4, 45.0) 9.7 (5.6, 16.2) 16.9 (11.4, 24.5) 0.0 (0.0, 3.0) 15.3 (10.0, 22.7) 10.5 (6.2, 17.1) 7.3 (3.9, 13.2) C (n=109) 63.3 (53.9, 71.8) 44.0 (35.1, 53.4) 6.4 (3.1, 12.7) 22.0 (15.3, 30.7) 17.4 (11.5, 25.6) 1.8 (0.5, 6.4) 21.1 (14.5, 29.7) 12.8 (7.8, 20.4) 12.8 (7.8, 20.4) D (n=176) 66.5 (59.2, 73.0) 48.0 (40.7, 55.4) 11.3 (7.4, 17.0) 18.4 (13.3, 24.8) 13.1 (8.9, 18.9) 0.0 (0.0, 2.1) 16.0 (11.3, 22.2) 9.2 (5.7, 14.4) 8.6 (5.3, 13.7) E (n=140) 66.9 (58.7, 74.2) 47.9 (39.8, 56.1) 7.9 (4.4, 13.5) 22.9 (16.7, 30.5) 20.0 (14.2, 27.4) 0.7 (0.1, 3.9) 22.1 (16.1, 29.7) 17.1 (11.8, 24.2) 8.6 (5.0, 14.4) F (n=267) 60.7 (54.7, 66.3) 36.7 (31.1, 42.6) 6.7 (4.3, 10.4) 17.2 (13.2, 22.2) 13.5 (9.9, 18.1) 0.0 (0.0, 1.4) 22.9 (18.3, 28.3) 9.8 (6.8, 13.9) 7.5 (4.9, 11.3) G (n=40) 56.4 (41.0, 70.7) 20.5 (10.8, 35.5) 5.6 (1.5, 18.1) 6.1 (1.7, 19.6) 5.6 (1.5, 18.1) 0.0 (0.0, 9.9) 10.3 (4.1, 23.6) 5.6 (1.5, 18.1) 7.7 (2.7, 20.3) H (n=170) 72.9 (65.8, 79.1) 12.0 (7.9, 17.9) 38.2 (31.3, 45.7) 18.8 (13.7, 25.4) J (n=140) 35.5 (28.0, 43.8) 6.7 (3.6, 12.3) 10.9 (6.7, 17.3) 0.8 (0.1, 4.2) 20.0 (14.1, 27.5) 6.0 (3.1, 11.4) 6.7 (3.5, 12.2) K (n=109) 50.5 (41.2, 59.7) 26.9 (19.4, 35.9) 7.3 (3.8, 13.8) 10.1 (5.7, 17.2) 11.9 (7.1, 19.3) 0.0 (0.0, 3.4) 19.3 (13.0, 27.7) 10.1 (5.7, 17.2) 11.9 (7.1, 19.3) L (n=123) 69.7 (61.0, 77.1) 54.1 (45.3, 62.7) 7.4 (3.9, 13.4) 21.5 (15.1, 29.6) 19.0 (13.0, 26.9) 0.0 (0.0, 3.0) 29.3 (22.0, 37.8) 16.5 (11.0, 24.2) 16.4 (10.9, 24.0) M (n=111) 61.8 (52.5, 70.4) 38.2 (29.6, 47.5) 3.7 (1.4, 9.1) 12.7 (7.7, 20.2) 11.8 (7.0, 19.2) 0.0 (0.0, 3.4) 17.4 (11.5, 25.6) 8.3 (4.4, 15.0) 3.6 (1.4, 9.0) N (n=83) 64.6 (53.8, 74.1) 48.2 (37.8, 58.8) 10.8 (5.6, 19.9) 14.6 (8.6, 23.9) 15.7 (9.4, 25.0) 0.0 (0.0, 4.4) 24.4 (16.4, 34.7) 14.6 (8.6, 23.9) 11.0 (5.9, 19.6) P (n=69) 76.8 (65.6, 85.2) 58.0 (46.2, 68.9) 14.5 (8.1, 24.7) 31.9 (22.1, 43.6) 27.5 (18.4, 39.0) 1.4 (0.3, 7.8) 42.0 (31.1, 53.8) 24.6 (16.0, 36.0) 15.9 (9.1, 26.3) Q (n=11) 81.8 (52.3, 94.9) 63.6 (35.4, 84.8) 18.2 (5.1, 47.7) 36.4 (15.2, 64.6) 36.4 (15.2, 64.6) 0.0 (0.0, 25.9) 45.5 (21.3, 72.0) 36.4 (15.2, 64.6) 27.3 (9.7, 56.6) R (n=46) 43.5 (30.2, 57.8) 8.7 (3.4, 20.3) 13.0 (6.1, 25.7) 0.0 (0.0, 7.9) 33.3 (21.4, 47.9) 11.1 (4.8, 23.5) 6.7 (2.3, 17.9) S (n=153) 69.9 (62.3, 76.6) 45.1 (37.4, 53.0) 7.2 (4.1, 12.4) 19.0 (13.5, 25.9) 15.0 (10.2, 21.5) 0.0 (0.0, 2.5) 22.4 (16.5, 29.6) 11.2 (7.1, 17.2) 5.9 (3.1, 10.9) T (n=39) 69.2 (53.6, 81.4) 48.7 (33.9, 63.8) 10.3 (4.1, 23.6) 20.5 (10.8, 35.5) 17.9 (9.0, 32.7) 0.0 (0.0, 9.0) 30.8 (18.6, 46.4) 17.9 (9.0, 32.7) 10.3 (4.1, 23.6) All-Wales: Resistance rates 65.2 (63.0, 67.3) 41.9 (39.6, 44.2) 8.3 (7.1, 9.6) 18.4 (16.6, 20.3) 15.3 (13.7, 17.0) 0.3 (0.1, 0.6) 23.3 (21.5, 25.3) 11.8 (10.4, 13.4) 9.9 (8.6, 11.3) All-Wales: Number of isolates 1885 1797 1937 1648 1802 1841 1958 1792 1959 Key: AMO = amoxicillin, COA = co-amoxiclav, PTZ = piperacillin/tazobactam, 3GC = resistance to ceftazidime &/or cefotaxime, cefpodoxime, ceftriaxone, CARB = ertapenem, imipenem &/or meropenem, FQ = ciprofloxacin &/or levofloxacin, 3GC/FQ = resistance to any third generation cephalosporin plus resistance to any fluoroquinolone, GEN = gentamicin Note: The range of resistance is outlined with boxes e.g. the range of resistance to amoxicillin was 56.4% - 81.8%; individual hospital rates statistically higher than the All-Wales rate are highlighted in blue. The resistance rates for E. coli bacteremia in Wrexham Maelor (H) and Llandough hospital (P) were notably higher to some of the agents tested suggesting a higher incidence of multi-resistant strains locally. Carbapenem resistant E. coli were reported; in most instances these isolates were reported as resistant to ertapnem and sensitive to imipenem and meropenem, however, one isolate was reported as resistant to imipenem and sensitive to ertapenem and meropenem. Carbapenem resistance was unconfirmed. 11

2012 Resistance (%) Escherichia coli (n=1977 in 2012) E. coli is the commonest organism grown from blood cultures in Wales and the UK. The All-Wales patterns of resistance for 2005 to 2012 are shown in Figure 1, and the All-Wales and individual hospital resistance rates for 2012 are shown in Table 3. 50.0 45.0 40.0 35.0 30.0 25.0 20.0 15.0 10.0 5.0 0.0 3GC COA CARB CXM FQ GEN PTZ Figure 1: All-Wales resistance rates for E. coli bacteraemia (2005 to 2012). The resistance rates for all of the antimicrobial agents increased between 2011 and 2012: Carbapenem resistance is unconfirmed. The resistance rates for Wales are comparable to the rates published by Public Health England below (Table 4). Table 4: PHE data for E. coli bacteraemia 2005-2012 E. coli 2005 2006 2007 2008 2009 2010 2011 2012 Total reports: 18,593 19,983 22,121 23,969 25,671 27,055 29,851 30,099 Cefotaxime Ceftazidime Ciprofloxacin Gentamicin Imipenem Meropenem % Non-susceptibility 9% 11% 12% 11% 10% 10% 11% 11% Reports with susceptibility data 7,259 9,013 10,464 11,725 12,793 13,494 15,393 16,322 % Non-susceptibility 9% 12% 12% 11% 10% 10% 11% 10% Reports with susceptibility data 9,672 11,304 14,586 15,977 16,512 18,44 20,798 20,200 % Non-susceptibility 19% 23% 23% 21% 20% 19% 19% 19% Reports with susceptibility data 13,948 15,908 18,412 19,531 20,069 21,825 24,796 25,505 % Non-susceptibility 8% 9% 9% 8% 8% 9% 9% 10% Reports with susceptibility data 14,649 16,090 19,180 21,124 22,112 23,637 26,711 27,402 % Non-susceptibility 0% 0% 0% 0% 0% 0% 0% 0% Reports with susceptibility data 4,783 5,481 7,218 7,361 7,222 6,461 5,755 4,937 % Non-susceptibility 0% 0% 0% 0% 0% 0% 0% 0% Reports with susceptibility data 4,690 5,973 9,132 11,730 13,529 15,441 19,296 20,285 12

There is currently no published European resistance data for the UK for 2012 so comparisons between the 2011 data sets have been made. In 2012, the resistance rate for 3GC generated from the Welsh data was 15.3%, comparable to the UK rate of 10 to <25% published by EARSS (see Figure 2). For the fluoroquinolones, the rate of 23.3% from the Welsh data is comparable to UK rate of 10 to <25% published by EARSS (see Figure 3). The UK data for EARS-Net is collected by a different method to the data published by the HPA, which may explain the difference in the UK rates for 3GC and fluoroquinolones from the two sources. Figure 2: Third generation cephalosporin resistance rates for E. coli bacteraemia (Data from EARS-Net) Figure 3: Fluoroquinolone resistant rates for E. coli bacteraemia (Data from EARS-Net) 13

Table 5: Klebsiella spp. TABLE 5: Klebsiella spp. from blood cultures Resistance rates including (95% Confidence Intervals) Duplicate Cut Off: 14 days Time period: 1 January - 31 December 2012 Location Code COA (95% CI) PTZ (95% CI) CXM (95% CI) 3GC (95% CI) CARB (95% CI) FQ (95% CI) 3GC/FQ (95% CI) GEN (95% CI) B (n=20) 22.2 (9.0, 45.2) 5.6 (1.0, 25.8) 5.6 (1.0, 25.8) 0.0 (0.0, 17.6) 5.6 (1.0, 25.8) 0.0 (0.0, 17.6) 0.0 (0.0, 17.6) C (n=19) 26.3 (11.8, 48.8) 21.1 (8.5, 43.3) 31.6 (15.4, 54.0) 21.1 (8.5, 43.3) 5.3 (0.9, 24.6) 21.1 (8.5, 43.3) 15.8 (5.5, 37.6) 10.5 (2.9, 31.4) D (n=41) 17.1 (8.5, 31.3) 7.7 (2.7, 20.3) 10.3 (4.1, 23.6) 4.9 (1.3, 16.1) 0.0 (0.0, 8.8) 7.3 (2.5, 19.4) 2.4 (0.4, 12.6) 2.5 (0.4, 12.9) E (n=34) 17.6 (8.3, 33.5) 0.0 (0.0, 10.2) 20.6 (10.3, 36.8) 5.9 (1.6, 19.1) 0.0 (0.0, 10.2) 2.9 (0.5, 14.9) 0.0 (0.0, 10.2) 5.9 (1.6, 19.1) F (n=72) 11.3 (5.8, 20.7) 6.9 (3.0, 15.2) 13.9 (7.7, 23.7) 5.6 (2.2, 13.4) 0.0 (0.0, 5.1) 6.9 (3.0, 15.2) 4.2 (1.4, 11.5) 1.4 (0.2, 7.5) H (n=26) 7.7 (2.1, 24.1) 3.8 (0.7, 18.9) 3.8 (0.7, 18.9) J (n=38) 18.4 (9.2, 33.4) 10.5 (4.2, 24.1) 2.6 (0.5, 13.5) 0.0 (0.0, 9.2) 2.6 (0.5, 13.5) 2.6 (0.5, 13.5) 2.6 (0.5, 13.5) K (n=30) 13.3 (5.3, 29.7) 3.3 (0.6, 16.7) 16.7 (7.3, 33.6) 13.3 (5.3, 29.7) 0.0 (0.0, 11.4) 10.0 (3.5, 25.6) 10.0 (3.5, 25.6) 13.3 (5.3, 29.7) L (n=30) 23.3 (11.8, 40.9) 16.7 (7.3, 33.6) 20.0 (9.5, 37.3) 16.7 (7.3, 33.6) 6.7 (1.8, 21.3) 13.3 (5.3, 29.7) 6.7 (1.8, 21.3) 0.0 (0.0, 11.4) M (n=15) 20.0 (7.0, 45.2) 6.7 (1.2, 29.8) 6.7 (1.2, 29.8) 6.7 (1.2, 29.8) 0.0 (0.0, 20.4) 0.0 (0.0, 20.4) 0.0 (0.0, 20.4) 0.0 (0.0, 20.4) N (n=21) 19.0 (7.7, 40.0) 9.5 (2.7, 28.9) 15.8 (5.5, 37.6) 0.0 (0.0, 15.5) 0.0 (0.0, 15.5) 0.0 (0.0, 15.5) 0.0 (0.0, 15.5) 0.0 (0.0, 15.5) S (n=30) 13.3 (5.3, 29.7) 6.7 (1.8, 21.3) 3.3 (0.6, 16.7) 3.3 (0.6, 16.7) 0.0 (0.0, 11.4) 3.3 (0.6, 16.7) 0.0 (0.0, 11.4) 3.3 (0.6, 16.7) All-Wales: Resistance rates 17.1 (13.7, 21.1) 8.4 (6.1, 11.5) 15 (11.6, 19.0) 7.2 (5.0, 10.2) 0.8 (0.3, 2.2) 6.7 (4.7, 9.5) 3.6 (2.1, 5.9) 3.1 (1.8, 5.2) All-Wales: Number of isolates 392 416 361 391 395 419 391 418 Key: COA = co-amoxiclav, PTZ = piperacillin/tazobactam, 3GC = resistance to ceftazidime &/or cefotaxime, cefpodoxime, ceftriaxone, CARB = imipenem &/or meropenem, FQ = ciprofloxacin &/or levofloxacin, 3GC/FQ = resistance to any third generation cephalosporin plus resistance to any fluoroquinolone, GEN = gentamicin Note: The resistance rates for Klebsiella spp. bacteremia at hospital level were not statistically different to the All-Wales rates except for gentamicin resistance in Ysbyty Gwynedd (K); however, Royal Glamorgan (C) had notably higher resistance rates to most of the agents tested. The combined resistance rates for third generation cephalosporins and fluoroquinolones (3GC/FQ) were also higher for this hospital suggesting a higher incidence of multi-resistant strains locally. Royal Glamorgan (C) and Ysbyty Glan Clwyd (L) were the only hospital to report nonsusceptibility to a carbapenem; there were two isolates, one that was reported as resistant to ertapenem, imipenem and intermediate to meropenem, and one reported as resistant to imipenem, whilst ertapenem and meropenem were not tested. 14

2006 2005 2012 Resistance (%) Klebsiella spp. (n=421 in 2012) The All-Wales patterns of antimicrobial resistance in Klebsiella spp. are shown in Figure 4 and Table 5; with no significant difference in resistance rates between 2011 and 2012. 34 32 30 28 26 24 22 20 18 16 14 12 10 8 6 4 2 0 3GC COA CARB CXM FQ GEN PTZ Figure 4: All-Wales antimicrobial resistance rates for Klebsiella species; isolated from blood culture (2005 to 2012) There is currently no PHE data for the UK for 2012 so comparisons between the 2011 data sets have been made. The Welsh resistance rates for 2011 are is generally lower than the Klebsiella spp. bacteraemia data published by the PHE (see Table 6 below). Table 6: PHE data for Klebsiella species bacteraemia 2005-2011 Klebsiella spp. 2005 2006 2007 2008 2009 2010 2011 Total reports: 5,150 5,551 6,001 6,099 6,160 6,133 6,595 Piperacillin/ Tazobactam Imipenem/ Meropenem Cefotaxime Ceftazidime Ciprofloxacin Gentamicin % Non-susceptibility 14% 15% 14% 11% 10% 11% 12% Reports with susceptibility data 2,699 3,330 4,046 4,533 4,485 4,635 5,218 % Non-susceptibility 0% 0% 0.3% 0.5% 0.3% 0.4% 0.8% Reports with susceptibility data 2,725 3,320 4,052 4,461 4,422 4,407 4,852 % Non-susceptibility 16% 15% 14% 10% 8% 9% 9% Reports with susceptibility data 2,133 2,739 2,839 2,984 3,132 3,061 3,393 % Non-susceptibility 16% 17% 15% 11% 9% 9% 9% Reports with susceptibility data 2,693 3,245 3,907 4,126 4,009 4,195 4,619 % Non-susceptibility 15% 17% 16% 11% 9% 8% 8% Reports with susceptibility data 3,757 4,408 4,809 4,887 4,743 4,897 5,375 % Non-susceptibility 9% 10% 10% 7% 6% 6% 6% Reports with susceptibility data 3,965 4,464 5,175 5,333 5,198 5,276 5,860 15

There is currently no published European resistance data for the UK for 2012 so comparisons between the 2011 data sets have been made. In 2011, the resistance rate for 3GC generated from the Welsh data was 7.2%, comparable to the UK rate of 5-10% published by EARSS (see Figure 5). For the fluoroquinolones, the rate of 6.7% from the Welsh data is comparable to UK rate of 5-10% published by EARSS (see Figure 6). Figure 5: Third generation cephalosporin resistance rates for K. pneumoniae bacteraemia (Data from EARS-Net) Figure 6: Fluoroquinolone resistance rates for K. pneumoniae bacteraemia (Data from EARS-Net) 16

Table 7: Enterobacter spp., Serratia spp., Proteus spp., and Pseudomonas aeruginosa TABLE 7: 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 2012 Organism AMO (95% CI) COA (95% CI) PTZ (95% CI) CXM (95% CI) 3GC (95% CI) CARB (95% CI) FQ (95% CI) 3GC/FQ (95% CI) GEN (95% CI) Enterobacter spp. 98.5 (94.8, 99.6) 97.7 (93.5, 99.2) 8.6 (5.0, 14.4) 90.5 (84.1, 94.5) 22.9 (16.5, 30.8) 2.3 (0.8, 6.5) 5.1 (2.5, 10.1) 5.5 (2.7, 10.9) 9.4 (5.5, 15.3) All-Wales: Number of isolates 137 132 140 126 131 131 138 128 139 Serratia spp. 99.0 (94.5, 99.8) 95.9 (89.9, 98.4) 14.4 (8.8, 22.8) 98.9 (94.1, 99.8) 35.7 (26.9, 45.6) 4.2 (1.6, 10.2) 32.0 (23.7, 41.7) 32 (23.5, 41.8) 2 (0.6, 7.1) All-Wales: Number of isolates 99 97 97 92 98 96 100 97 99 Proteus spp. 42.3 (34.4, 50.5) 22.5 (16.4, 30.1) 2.7 (1.1, 6.8) 9.6 (5.6, 16.0) 2.1 (0.7, 5.9) 19.0 (13.3, 26.4) 6 (3.2, 11.0) 1.4 (0.4, 5.0) 33.1 (26.1, 41.0) All-Wales: Number of isolates 142 142 147 125 144 137 150 141 151 Pseudomonas aeruginosa 6.6 (3.8, 11.2) 5.2 (2.8, 9.6) 20.9 (15.6, 27.4) 12 (8.0, 17.4) 2.7 (1.2, 6.2) All-Wales: Number of isolates 181 173 182 184 184 Key: AMO = amoxicillin, COA = co-amoxiclav, PTZ = piperacillin/tazobactam, CXM = cefuroxime, 3GC = resistance to ceftazidime &/or cefotaxime, cefpodoxime, ceftriaxone, CARB = ertapenem, imipenem &/or meropenem, FQ = ciproflxacin &/or levofloxacin, 3GC/FQ = resistance to any third generation cephalosporin plus resistance to any fluoroquinolone, GEN = gentamicin. a for Pseudomonas aeruginosa 3GC = ceftazidime only. 17

2005 2012 Resistance (%) Enterobacter spp. (n=143 in 2012) The All-Wales patterns of antimicrobial resistance for Enterobacter spp. are shown in Figure 7 and Table 7. There have been significant decreases in resistance rates between 2005 and 2012 except for gentamicin which has increased in 2012; most of these changes are in line with those reported by the HPA (see Table 8). 65 60 55 50 45 40 35 30 25 20 15 10 5 0 Figure 7: All-Wales antimicrobial resistance rates for Enterobacter species; isolated from blood culture (2005 to 2012) The significant decrease in resistance between 2005 and 2011 reported by the HPA is reflected in the Welsh data. Note: Although the rates of carbapenem resistance in Wales are higher than those reported by the HPA, the Wales figure represents ertapenem resistance, and not imipenem or meropenem resistance. Table 8: HPA data for Enterobacter species bacteraemia 2005-2011 Enterobacter spp. 2005 2006 2007 2008 2009 2010 2011 Total reports: 2,522 2,613 2,675 2,403 2,196 2,037 2,050 Piperacillin/ Tazobactam Imipenem/ Meropenem Cefotaxime Ceftazidime Ciprofloxacin Gentamicin 3GC CARB FQ GEN PTZ % Non-susceptibility 23% 24% 21% 18% 17% 18% 16% Reports with susceptibility data 1,368 1,594 1,884 1,778 1,546 1,484 1,561 % Non-susceptibility 1% 1.2% 1.1% 0.7% 0.4% 1.0% 1.0% Reports with susceptibility data 1,506 1,732 1,984 1,904 1,613 1,524 1,561 % Non-susceptibility 40% 42% 37% 38% 35% 33% 29% Reports with susceptibility data 1,040 1,213 1,271 1,188 1,076 993 1,012 % Non-susceptibility 42% 41% 36% 36% 32% 32% 29% Reports with susceptibility data 1,334 1,519 1,769 1,607 1,368 1,372 1,390 % Non-susceptibility 15% 14% 10% 8% 6% 5% 5% Reports with susceptibility data 1,860 2,092 2,237 1,980 1,684 1,632 1,682 % Non-susceptibility 12% 11% 9% 8% 7% 5% 6% Reports with susceptibility data 1,988 2,108 2,337 2,132 1,834 1,723 1,801 18

2005 2012 Resistance (%) Serratia spp. (n=101 in 2012) The All-Wales patterns of antimicrobial resistance for Serratia spp. are shown in Figure 8 and Table 7. There has been a statistically significant decrease in resistance rates third generation cephalosporins (3GC), fluoroquinolones (FQ) and piperacillin/tazobactam (PTZ) between 2005 and 2012. 75 70 65 60 55 50 45 40 35 30 25 20 15 10 5 0 3GC CARB FQ GEN PTZ Figure 8: All-Wales antimicrobial resistance rates for Serratia species; isolated from blood culture (2005 to 2012) The significant decrease in resistance between 2007 and 2011 reported by the HPA is reflected in the Welsh data. The reported rates of resistance to the third generation cephalosporins (42% in 2011) and fluoroquinolones (43% in 2011) for Wales were significantly higher than rates reported for the relevant single agents by the HPA (see Table 9). This may be due to methodological issues in testing and reporting rather than genuine geographical variability in susceptibility. Table 9: HPA data for Serratia species bacteraemia 2005-2011 Serratia spp. 2005 2006 2007 2008 2009 2010 2011 Total reports: 1,158 1,270 1,208 1,071 992 943 886 Piperacillin/ Tazobactam Imipenem/ Meropenem Cefotaxime Ceftazidime Ciprofloxacin Gentamicin % Non-susceptibility 20% 20% 16% 16% 12% 15% 10% Reports with susceptibility data 604 774 828 764 712 712 707 % Non-susceptibility 0% 1% 0.3% 0.6% 0.1% 0.5% 0.4% Reports with susceptibility data 642 807 888 821 780 780 702 % Non-susceptibility 27% 29% 28% 28% 30% 29% 22% Reports with susceptibility data 426 548 582 537 541 497 459 % Non-susceptibility 18% 16% 14% 22% 20% 21% 16% Reports with susceptibility data 549 681 742 678 647 681 644 % Non-susceptibility 26% 25% 20% 16% 12% 12% 11% Reports with susceptibility data 854 996 1,007 864 800 794 756 % Non-susceptibility 2% 2% 1% 3% 3% 2% 1% Reports with susceptibility data 1,002 1,002 1.046 917 855 838 823 19

Resistance (%) Proteus spp. (n=154 in 2012) The All-Wales patterns of antimicrobial resistance in Proteus spp. are shown in Figure 9 & Table 7, with no statistically significant changes between 2011 and 2012 but with a marked increase in resistance to gentamicin. 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 35 30 25 20 15 10 5 0 Figure 9: All-Wales antimicrobial resistance rates for Proteus species; isolated from blood culture (2005 to 2012) The HPA 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 HPA resistance rates for Proteus mirabilis 2006-2012 are shown for comparison with the Welsh data (see Figure 9 and Table 10). Table 10: HPA data for Proteus mirabilis bacteraemia 2005-2012 Proteus mirabilis 2006 2007 2007 2009 2010 2011 2012 Total reports: 1,671 1,842 2,083 2,133 2,091 2,091 2,238 Amoxicillin Cefuroxime Cefotaxime Ceftazidime Ciprofloxacin Gentamicin Imipenem 3GC AMO COA CARB CXM FQ GEN PTZ % Non-susceptibility 35% 30% 31% 32% 33% 34% 34% Reports with susceptibility 1,289 1,459 1,719 1,660 1,690 1,793 1,909 % Non-susceptibility 5% 2% 2% 1% 2% 2% 1% Reports with susceptibility 1,234 1,369 1,476 1,323 1,311 1,458 1,477 % Non-susceptibility 5% 1% 1% 0% 1% 2% 2% Reports with susceptibility 743 858 983 1,044 1,005 1,0734 1,160 % Non-susceptibility 2% 1% 1% 1% 1% 2% 2% Reports with susceptibility 916 1,190 1,355 1,380 1,383 1,517 1,512 % Non-susceptibility 7% 7% 6% 6% 6% 7% 9% Reports with susceptibility 1,293 1,460 1,648 1,622 1,677 1,775 1,857 % Non-susceptibility 4% 4% 3% 6% 7% 7% 10% Reports with susceptibility 1,296 1,527 1,816 1,779 1,795 1,897 2,000 % Non-susceptibility 1% 2% 4% 6% 8% 9% 5% Reports with susceptibility 389 529 591 524 407 339 247 20

2005 2012 Resistance (%) Pseudomonas aeruginosa (n=188 in 2012) The All-Wales patterns of antimicrobial resistance in Pseudomonas aeruginosa are shown in Figure 10 & Table 7. 35 30 25 20 15 10 5 0 CARB CAZ CIP GEN PTZ Figure 10: All-Wales antimicrobial resistance rates for Pseudomonas aeruginosa; isolated from blood culture (2005 to 2012) There was no statistically significant increase in resistance rates between 2011 and 2012. The HPA rates are shown below for comparison with the Welsh data (see Figure 10 and Table 11). http://www.hpa.org.uk/topics/infectiousdiseases/infectionsaz/bacteraemia/ Table 11: HPA data for Pseudomonas aeruginosa bacteraemia 2005-2011 Pseudomonas aeruginosa 2006 2007 2007 2009 2010 2011 Total reports: 2,866 3,090 3,142 3,248 3,192 3,108 Piperacillin/ Tazobactam % Non-susceptibility 4% 5% 6% 8% 7% 7% Reports with susceptibility data 1,985 2,324 2,489 2,509 2,570 2,542 Imipenem % Non-susceptibility 11% 12% 9% 13% 12% 14% Reports with susceptibility data 965 1,147 1,111 1,172 1,038 924 Meropenem Ceftazidime Ciprofloxacin Gentamicin % Non-susceptibility 10% 9% 10% 11% 9% 9% Reports with susceptibility data 1,087 1,396 1,713 1,785 2,017 2,210 % Non-susceptibility 7% 8% 7% 8% 8% 8% Reports with susceptibility data 2,213 2,514 2,483 2,461 2,530 2,524 % Non-susceptibility 12% 12% 11% 11% 10% 11% Reports with susceptibility data 2,393 2,646 2,656 2,709 2,696 2,701 % Non-susceptibility 5% 5% 4% 4% 5% 6% Reports with susceptibility data 2,415 2,754 2,784 2,778 2,812 2,808 21

Staphylococcus aureus bacteraemias 2012 Table 12: Staphylococcus aureus (MSSA & MRSA) TABLE 12: Staphylococcus aureus from blood cultures (MSSA & MRSA) Resistance rates including (95% Confidence Intervals) Duplicate Cut Off: 14 days Time period: 1 January - 31 December 2012 Location (Number BC) ERY (95% CI) FLU (95% CI) FUS (95% CI) GEN (95% CI) LZD (95% CI) MUP (95% CI) RIF (95% CI) TET (95% CI) VAN (95% CI) A (n=10) 11.1 (2.0, 43.5) 10.0 (1.8, 40.4) B (n=54) 17.6 (9.6, 30.3) 13.0 (6.4, 24.4) 9.8 (4.3, 21.0) 0.0 (0.0, 7.4) 2.0 (0.4, 10.5) 0.0 (0.0, 7.1) 1.9 (0.3, 10.1) C (n=35) 15.6 (6.9, 31.8) 17.1 (8.1, 32.7) 14.7 (6.4, 30.1) 5.9 (1.6, 19.1) 0.0 (0.0, 10.2) 0.0 (0.0, 10.2) 0.0 (0.0, 10.2) 2.9 (0.5, 14.9) 0.0 (0.0, 9.9) D (n=83) 25.9 (17.6, 36.4) 18.1 (11.3, 27.7) 11.8 (6.4, 21.0) 5.1 (2.0, 12.3) 0.0 (0.0, 4.8) 6.6 (2.8, 14.5) E (n=62) 21.3 (12.9, 33.1) 25.8 (16.6, 37.9) 16.4 (9.2, 27.6) 6.6 (2.6, 15.7) 0.0 (0.0, 6.5) 7.3 (2.9, 17.3) 0.0 (0.0, 6.5) 3.4 (0.9, 11.5) F (n=159) 24.1 (18.1, 31.3) 20.1 (14.6, 27.0) 11.9 (7.8, 17.9) 4.4 (2.1, 8.8) 0.0 (0.0, 2.4) 1.9 (0.6, 5.4) 0.0 (0.0, 2.4) 3.8 (1.8, 8.0) 0.0 (0.0, 2.4) G (n=26) 15.4 (6.1, 33.5) 19.2 (8.5, 37.9) 4.0 (0.7, 19.5) 0.0 (0.0, 14.3) 0.0 (0.0, 13.3) 0.0 (0.0, 14.3) 0.0 (0.0, 12.9) 0.0 (0.0, 14.3) H (n=48) 36.6 (23.6, 51.9) 25.0 (14.9, 38.8) 19.6 (10.7, 33.2) 0.0 (0.0, 8.4) J (n=44) 18.2 (9.5, 32.0) 20.5 (11.2, 34.5) 17.9 (9.0, 32.7) 7.7 (2.7, 20.3) 0.0 (0.0, 9.0) 2.6 (0.5, 13.2) K (n=50) 42.0 (29.4, 55.8) 38.0 (25.9, 51.8) 16.0 (8.3, 28.5) 4.0 (1.1, 13.5) 2.0 (0.4, 10.7) 6.0 (2.1, 16.2) 0.0 (0.0, 7.1) L (n=70) 35.7 (25.5, 47.4) 27.1 (18.1, 38.5) 17.1 (10.1, 27.6) 0.0 (0.0, 5.2) 2.9 (0.8, 10.0) 0.0 (0.0, 5.3) 8.6 (4.0, 17.5) 0.0 (0.0, 5.3) M (n=49) 14.6 (7.2, 27.2) 10.2 (4.4, 21.8) 2.2 (0.4, 11.3) 8.3 (3.3, 19.6) 0.0 (0.0, 7.7) 2.2 (0.4, 11.3) N (n=38) 23.7 (13.0, 39.2) 26.3 (15.0, 42.0) 15.8 (7.4, 30.4) 10.5 (4.2, 24.1) 0.0 (0.0, 9.4) 3.1 (0.6, 15.7) 0.0 (0.0, 9.2) 10.8 (4.3, 24.7) 0.0 (0.0, 9.2) P (n=25) 12.0 (4.2, 30.0) 12.0 (4.2, 30.0) 8.0 (2.2, 25.0) 0.0 (0.0, 13.3) 0.0 (0.0, 13.3) 4.0 (0.7, 19.5) 0.0 (0.0, 13.3) 0.0 (0.0, 13.3) 0.0 (0.0, 13.3) R (n=18) 5.6 (1.0, 25.8) 5.6 (1.0, 25.8) 12.5 (3.5, 36.0) 0.0 (0.0, 19.4) 0.0 (0.0, 19.4) 0.0 (0.0, 19.4) S (n=71) 12.7 (6.8, 22.4) 11.3 (5.8, 20.7) 18.3 (11.0, 28.8) 1.4 (0.2, 7.6) 0.0 (0.0, 5.3) 0.0 (0.0, 5.3) 0.0 (0.0, 5.3) 2.8 (0.8, 9.7) T (n=11) 9.1 (1.6, 37.7) 27.3 (9.7, 56.6) 0.0 (0.0, 25.9) 0.0 (0.0, 25.9) 0.0 (0.0, 25.9) All-Wales: Resistance rates 22.7 (20.0, 25.7) 19.9 (17.4, 22.7) 13.2 (11.1, 15.7) 4.1 (2.9, 5.8) 0.0 (0.0, 0.6) 2.9 (1.9, 4.5) 0.3 (0.1, 1.1) 4.6 (3.3, 6.3) 0.0 (0.0, 0.6) All-Wales: Number of isolates 860 860 831 755 673 713 658 724 650 Key: ERY = erythromycin, FLU= flucloxacillin, FUS = fusidic acid, GEN = gentamicin, LZD = linezolid, MUP = mupirocin, RIF = rifampicin, TET = tetracycline, VAN = vancomycin. Table 12 shows the resistance rates for Staphylococcus aureus at hospital level Note: The data includes all Staphylococcus aureus (MSSA and MRSA). The range of resistance for each antibacterial is outlined e.g. the range of resistance to erythromycin was 5.6% - 42.0%; individual hospital rates that are statistically higher than the All-Wales rate are highlighted in blue. The resistance rates for S. aureus bacteraemias in Ysbyty Gwynedd were notably high to flucloxacillin 38.0% (95% CI - 25.9, 51.8), and shows a higher prevalence of MRSA in this locality than in other hospitals in Wales. 22

Table 13: Meticillin Sensitive Staphylococcus aureus TABLE 13: Meticillin Sensitive Staphylococcus aureus from blood cultures Resistance rates including (95% Confidence Intervals) Duplicate Cut Off: 14 days Time period: 1 January - 31 December 2012 Location Code ERY (95% CI) FUS (95% CI) GEN (95% CI) LZD (95% CI) MUP (95% CI) PEN (95% CI) RIF (95% CI) TET (95% CI) VAN (95% CI) B (n=47) 13.0 (6.1, 25.7) 10.9 (4.7, 23.0) 0.0 (0.0, 8.2) 0.0 (0.0, 7.9) 91.3 (79.7, 96.6) 0.0 (0.0, 7.9) 2.1 (0.4, 11.1) C (n=29) 7.7 (2.1, 24.1) 14.3 (5.7, 31.5) 7.1 (2.0, 22.6) 0.0 (0.0, 12.1) 0.0 (0.0, 12.1) 0.0 (0.0, 12.1) 3.6 (0.6, 17.7) 0.0 (0.0, 11.7) D (n=68) 16.7 (9.6, 27.4) 9.7 (4.5, 19.5) 6.2 (2.4, 14.8) 0.0 (0.0, 5.8) 6.5 (2.5, 15.4) 88.9 (78.8, 94.5) E (n=46) 17.4 (9.1, 30.7) 15.2 (7.6, 28.2) 2.2 (0.4, 11.3) 0.0 (0.0, 8.6) 2.4 (0.4, 12.6) 81.4 (67.4, 90.3) 0.0 (0.0, 8.6) 4.4 (1.2, 14.8) F (n=127) 12.7 (8.0, 19.6) 10.2 (6.1, 16.7) 4.7 (2.2, 9.9) 0.0 (0.0, 2.9) 0.8 (0.1, 4.3) 100 (96.3, 100) 0.0 (0.0, 2.9) 4.0 (1.7, 9.0) 0.0 (0.0, 2.9) G (n=21) 14.3 (5.0, 34.6) 4.8 (0.8, 22.7) 0.0 (0.0, 16.8) 0.0 (0.0, 16.1) 81.0 (60.0, 92.3) 0.0 (0.0, 16.8) 0.0 (0.0, 15.5) 0.0 (0.0, 16.8) H (n=36) 24.1 (12.2, 42.1) 11.8 (4.7, 26.6) 0.0 (0.0, 11.4) 0.0 (0.0, 10.2) J (n=35) 8.6 (3.0, 22.4) 16.7 (7.3, 33.6) 3.3 (0.6, 16.7) 0.0 (0.0, 11.4) 3.3 (0.6, 16.7) K (n=31) 12.9 (5.1, 28.9) 16.1 (7.1, 32.6) 6.5 (1.8, 20.7) 77.4 (60.2, 88.6) 3.3 (0.6, 16.7) 3.2 (0.6, 16.2) 0.0 (0.0, 11.0) L (n=51) 17.6 (9.6, 30.3) 11.8 (5.5, 23.4) 0.0 (0.0, 7.0) 4.0 (1.1, 13.5) 0.0 (0.0, 7.1) 2.0 (0.3, 10.3) 0.0 (0.0, 7.1) M (n=44) 9.3 (3.7, 21.6) 2.4 (0.4, 12.3) 6.8 (2.3, 18.2) 0.0 (0.0, 8.4) 2.4 (0.4, 12.3) 83.7 (70.0, 91.9) N (n=28) 7.1 (2.0, 22.6) 14.3 (5.7, 31.5) 10.7 (3.7, 27.2) 0.0 (0.0, 12.5) 88.0 (70.0, 95.8) 0.0 (0.0, 12.1) 11.1 (3.9, 28.1) 0.0 (0.0, 12.1) P (n=22) 4.5 (0.8, 21.8) 9.1 (2.5, 27.8) 0.0 (0.0, 14.9) 0.0 (0.0, 14.9) 4.5 (0.8, 21.8) 100 (84.5, 100) 0.0 (0.0, 14.9) 0.0 (0.0, 14.9) 0.0 (0.0, 14.9) R (n=17) 5.9 (1.0, 27.0) 6.7 (1.2, 29.8) 0.0 (0.0, 20.4) 0.0 (0.0, 20.4) 0.0 (0.0, 20.4) S (n=63) 6.3 (2.5, 15.2) 17.5 (10.0, 28.6) 0.0 (0.0, 5.7) 0.0 (0.0, 6.0) 0.0 (0.0, 6.0) 91.7 (81.9, 96.4) 0.0 (0.0, 6.0) 3.2 (0.9, 10.9) All-Wales: Resistance rates 12.3 (10.1, 15.0) 11.4 (9.2, 14.1) 3.7 (2.5, 5.5) 0.0 (0.0, 0.7) 1.8 (1.0, 3.2) 90.2 (87.4, 92.5) 0.4 (0.1, 1.4) 3.0 (1.9, 4.8) 0.0 (0.0, 0.7) All-Wales: Number of isolates 673 666 595 544 570 533 514 565 514 Key: ERY = erythromycin, FUS = fusidic acid, GEN = gentamicin, LZD = linezolid, MUP = mupirocin, PEN = pencillin, RIF = rifampicin, TET = tetracycline, VAN = vancomycin. 23

2005 2012 Resistance (%) Meticillin Sensitive Staphylococcus aureus (n=689 in 2012) The All-Wales pattern of antimicrobial resistance in MSSA is shown in Figure 11 and Table 13; with no statistically significant changes between 2005 and 2012. 20 18 16 14 12 10 8 6 4 2 0 ERY FUS GEN MUP RIF Figure 11: All-Wales antimicrobial resistance rates for Meticillin Sensitive Staphylococcus aureus (MSSA) isolated from blood culture (2005 to 2012) The All-Wales antimicrobial resistance rates for MSSA are largely comparable to those published by BSAC for the UK except for gentamicin resistance which appears higher in Wales. In 2012, the All-Wales gentamicin resistance rate increased significantly to 3.7%. The rate is skewed by high local rates in some areas including Prince Charles (10.7%) and Royal Glamorgan (7.1%) hospitals. This presumably reflects the varying presence of epidemic strains. In 2012, resistance to penicillin was 90.2%, and resistance to vancomycin remained undetected. 24

Table 14: Meticillin Resistant Staphylococcus aureus TABLE 14: Meticillin Resistant Staphylococcus aureus from blood cultures Resistance rates including (95% Confidence Intervals) Duplicate Cut Off: 14 days Time period: 1 January - 31 December 2012 Location Code ERY (95% CI) FQ (95% CI) FUS (95% CI) GEN (95% CI) LZD (95% CI) MUP (95% CI) RIF (95% CI) TET (95% CI) VAN (95% CI) D (n=15) 66.7 (41.7, 84.8) 73.3 (48.0, 89.1) 21.4 (7.6, 47.6) 0.0 (0.0, 21.5) 0.0 (0.0, 20.4) 7.1 (1.3, 31.5) 13.3 (3.7, 37.9) E (n=16) 33.3 (15.2, 58.3) 92.9 (68.5, 98.7) 20.0 (7.0, 45.2) 20.0 (7.0, 45.2) 0.0 (0.0, 21.5) 21.4 (7.6, 47.6) 0.0 (0.0, 21.5) 0.0 (0.0, 21.5) 0.0 (0.0, 21.5) F (n=32) 68.8 (51.4, 82.0) 87.1 (71.1, 94.9) 18.8 (8.9, 35.3) 3.1 (0.6, 15.7) 0.0 (0.0, 10.7) 6.3 (1.7, 20.1) 0.0 (0.0, 11.4) 3.1 (0.6, 15.7) 0.0 (0.0, 11.4) H (n=12) 66.7 (39.1, 86.2) 41.7 (19.3, 68.0) 0.0 (0.0, 24.3) 0.0 (0.0, 24.3) 0.0 (0.0, 24.3) 0.0 (0.0, 24.3) 41.7 (19.3, 68.0) K (n=19) 89.5 (68.6, 97.1) 15.8 (5.5, 37.6) 0.0 (0.0, 16.8) 0.0 (0.0, 16.8) 10.5 (2.9, 31.4) 0.0 (0.0, 16.8) L (n=19) 84.2 (62.4, 94.5) 94.7 (75.4, 99.1) 31.6 (15.4, 54.0) 0.0 (0.0, 16.8) 0.0 (0.0, 16.8) 0.0 (0.0, 16.8) 26.3 (11.8, 48.8) 0.0 (0.0, 16.8) N (n=10) 70.0 (39.7, 89.2) 80.0 (49.0, 94.3) 20.0 (5.7, 51.0) 10.0 (1.8, 40.4) 0.0 (0.0, 27.8) 10.0 (1.8, 40.4) 0.0 (0.0, 27.8) 10.0 (1.8, 40.4) 0.0 (0.0, 27.8) All-Wales: Resistance rates 64.3 (56.8, 71.1) 87.2 (80.5, 91.9) 20.6 (15.1, 27.4) 5.6 (3.0, 10.3) 0.0 (0.0, 2.9) 7.7 (4.3, 13.2) 0.0 (0.0, 2.6) 10.1 (6.3, 15.7) 0.0 (0.0, 2.7) All-Wales: Number of isolates 168 133 165 160 129 143 144 159 136 Key: ERY = erythromycin, FQ = ciprofloxacin, FUS = fusidic acid, GEN = gentamicin, LZD = linezolid, MUP = mupirocin, RIF = rifampicin, TET = tetracycline, VAN = vancomycin. 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. Note: Locally resistance rates for fusidic acid and tetracycline were notably high in Wrexham Maelor (H), and for gentamicin and mupirocin notably high in Morriston (E); the rates were comparable with those noted in MRSA from wound swabs from the same locations (see Section 4.3). 25

2005 2012 2007 Resistance (%) Meticillin Resistant Staphylococcus aureus (n=171 in 2012) The All-Wales pattern of antimicrobial resistance in MRSA is shown in Figure 12 & Table 14; with a statistically significant decrease in erythromycin resistance between 2005 and 2012, and a statistically significant increase in fusidic acid resistance. 100 90 80 70 60 50 40 30 20 10 0 ERY FUS GEN MUP RIF Figure 12: All-Wales antimicrobial resistance rates for Meticillin Resistant Staphylococcus aureus (MRSA) isolated from blood culture (2005 to 2012) The All-Wales antimicrobial resistance rates for MRSA for 2005 to 2011 are largely comparable to those published by BSAC for the UK. BSAC have not as yet published antimicrobial resistance rates for MRSA for 2012. Resistance to vancomycin and linezolid has remained undetected. 26

Table 15: Enterococcus spp. TABLE 15: Enterococcus spp. from blood cultures Resistance rates including (95% Confidence Intervals) Duplicate Cut Off: 14 days Time period: 1 January - 31 December 2012 Location Code AMO (95% CI) VAN (95% CI) A (n=12) 66.7 (39.1, 86.2) 0.0 (0.0, 24.3) B (n=26) 19.0 (7.7, 40.0) 4.8 (0.8, 22.7) C (n=23) 52.2 (33.0, 70.8) 4.3 (0.8, 21.0) D (n=31) 33.3 (19.2, 51.2) 11.1 (3.9, 28.1) E (n=40) 40.0 (26.3, 55.4) 7.5 (2.6, 19.9) F (n=107) 51.4 (42.0, 60.7) 15.0 (9.4, 22.9) H (n=29) 41.4 (25.5, 59.3) 20.7 (9.8, 38.4) J (n=43) 35.7 (23.0, 50.8) 5.1 (1.4, 16.9) K (n=31) 58.1 (40.8, 73.6) 32.3 (18.6, 49.9) L (=36) 38.9 (24.8, 55.1) 22.2 (11.7, 38.1) M (n=16) 18.8 (6.6, 43.0) 0.0 (0.0, 49.0) N (n=19) 42.1 (23.1, 63.7) 15.8 (5.5, 37.6) S (n=28) 14.8 (5.9, 32.5) 0.0 (0.0, 12.1) All-Wales: Resistance rates 40.3 (35.9, 44.9) 12.3 (9.5, 15.7) All-Wales: Number of isolates 459 440 Key: AMO = amoxicillin, VAN = vancomycin. Note: Locally resistance rates for amoxicillin varied from 14.8% (Singleton - S) to 66.7% (Bronglais - A) and this may simply reflect variation in the proportion of E. faecalis to E. faecium. Vancomycin resistance varied from 0.0% (Bronglais - A, Nevill Hall - M, and Singleton - S) to 32.3% (Ysbyty Gwynedd - K). 27

2005 2012 Resistance (%) Enterococcus spp. (n=470 in 2012) The All-Wales pattern of antimicrobial resistance in Enterococcus spp. is shown in Figure 13 and Table 15; with no statistically significant changes between 2005 and 2012. 50 45 40 35 30 25 20 15 10 5 0 AMO Figure 13: All-Wales antimicrobial resistance rates for Enterococcus spp. isolated from blood culture (2005 to 2012) VAN In 2012, the All-Wales resistance rate for amoxicillin was 40.3% (35.9, 44.9). Susceptibility to amoxicillin is a guide to speciation of the organism, E. faecalis being normally susceptible and E. faecium being normally resistant, and suggests that in 2012, 59.57% of entercoccal bacteraemias were due to E. faecalis. This proportion is significantly higher than the figures for E. faecalis bacteraemias published by the HPA for 2011 (43.3%), however, it should be noted that a large proportion of the enterococci in the HPA data set were not identified to species level and the numbers may be more comparable than they appear on first inspection (see Table 16 below). Table 16: HPA data for Enterococcus spp. bacteraemia 2005-11 Enterococcus spp. 2005 2006 2007 2008 2009 2010 2011 Enterococcus faecalis 3,113 3,461 3,241 2,710 2,662 2,402 2,379 Enterococcus faecium 1,409 1,729 1,737 1,524 1,487 1,550 1,686 Enterococcus, other named species* 289 285 298 257 243 238 275 Enterococcus spp., species not recorded 2,115 2,152 2,202 1,663 1,404 1,207 1,148 Enterococcus spp. in total 6,926 7,627 7,478 6,154 5,796 5,397 5,488 *Other named species: Enterococcus gallinarum, Enterococcus avium, Enterococcus casseliflavus, Enterococcus durans, Enterococcus hirae, Enterococcus raffinosus. 28

Table 17: Streptococcus pneumoniae TABLE 17: Streptococcus pneumoniae from blood cultures Resistance rates including (95% Confidence Intervals) Duplicate Cut Off: 14 days Time period: 1 January - 31 December 2012 Location Code ERY (95% CI) PEN (95% CI) TET (95% CI) B (n=21) 23.8 (10.6, 45.1) 0.0 (0.0, 15.5) 15.0 (5.2, 36.0) C (n=19) 0.0 (0.0, 16.8) D (n=34) 5.9 (1.6, 19.1) 5.9 (1.6, 19.1) 6.7 (1.8, 21.3) F (n=26) 3.8 (0.7, 18.9) 7.7 (2.1, 24.1) 3.8 (0.7, 18.9) G (n=13) 7.7 (1.4, 33.3) 0.0 (0.0, 22.8) 0.0 (0.0, 22.8) H (n=27) 0.0 (0.0, 12.5) J (n=22) 4.5 (0.8, 21.8) 0.0 (0.0, 14.9) 0.0 (0.0, 14.9) K (n=16) 12.5 (3.5, 36.0) 6.3 (1.1, 28.3) 0.0 (0.0, 19.4) L (n=21) 14.3 (5.0, 34.6) 0.0 (0.0, 15.5) 4.8 (0.8, 22.7) M (n=14) 7.1 (1.3, 31.5) 0.0 (0.0, 21.5) 7.7 (1.4, 33.3) P (n=11) 9.1 (1.6, 37.7) 0.0 (0.0, 25.9) 9.1 (1.6, 37.7) S (n=29) 6.9 (1.9, 22.0) 3.4 (0.6, 17.2) All-Wales: Resistance rates 8.4 (5.6, 12.5) 2.0 (0.9, 4.4) 5.2 (3.0, 8.8) All-Wales: Number of isolates 250 295 232 Key: ERY = erythromycin, PEN = penicillin, TET = tetracycline. 29

2005 2012 Resistance (%) Streptococcus pneumoniae (n=295 in 2012) The All-Wales pattern of antimicrobial resistance is shown in Figure 14 & Table 17 (page 25); with no statistically significant changes between 2005 and 2012. 16 14 12 10 8 6 4 2 0 ERY PEN TET Figure 14: All-Wales antimicrobial resistance rates for Streptococcus pneumoniae isolated from blood culture (2005 to 2012) The All-Wales resistance rates for penicillin in 2011 was 2.7% which was lower than the 2011 UK intermediate resistance rate published by BSAC of 6.4%, and lower than the 5 to <10% range published by EARSS for 2011 (See Figure 15). Figure 15: Penicillin resistance rates for S. pneumoniae bacteraemia (Data from EARS-Net) 30

Section 4.2: Antimicrobial resistance rates for urinary coliforms For the purposes of this report the term coliform refers to organisms that were reported as a coliform by the laboratory, or when identified further, were reported as one of the genera belonging to the family Enterobacteriaceae. The genera included in this section of the report comprise: Citrobacter Edwardsiella Enterobacter Escherichia Hafnia Klebsiella Kluyvera Morganella Pantoea Proteus Providencia Rahnella Salmonella Serratia Yersinia It should be noted that data from routinely-submitted urine specimens is more prone to bias than data from blood culture isolates due to variable sampling by clinicians. Thus resistance rates quoted here are likely to be higher due to increased sampling from patients who are more likely to have resistant organisms (e.g. patients with recurrent infections or infections that have failed to respond to initial therapy). This should be factored into any use of the data presented for the design of empiric treatment guidance. The generation of more specific data reports (e.g. different patient age groups) can be discussed with the Welsh AR Programme. 31

Table 18: Community Urinary Coliforms TABLE 18: Community Urinary Coliforms (including E.coli and Proteus spp. ) Resistance rates including (95% Confidence Intervals) Duplicate Cut Off: 91 days Time period: 1 January - 31 December 2012 Location Code AMO (95% CI) COA (95% CI) IGC (95% CI) TRI (95% CI) AMO/TRI (95% CI) FQ (95% CI) AMO/TRI/FQ(95% CI) NIT (95% CI) CPD (95% CI) A (n=2,752) 53.8 (51.9, 55.7) 8.6 (7.6, 9.7) 6.9 (6.0, 7.9) 33.5 (31.7, 35.3) 24.7 (23.1, 26.4) 8.0 (7.0, 9.0) 5.5 (4.7, 6.4) 10.3 (9.2, 11.5) 2.7 (2.1, 3.3) B (n=451) 65.2 (60.7, 69.4) 11.8 (9.1, 15.1) 13.1 (10.3, 16.5) 30.2 (26.1, 34.5) 27.3 (23.4, 31.6) 12.6 (9.9, 16.0) 10.0 (7.5, 13.1) 9.5 (7.2, 12.6) 8.0 (5.9, 10.9) C (n=4,330) 62.0 (60.5, 63.4) 13.0 (12.0, 14.1) 10.0 (9.1, 11.1) 35.1 (33.7, 36.6) 29.1 (27.8, 30.5) 9.2 (8.4, 10.1) 6.7 (6.0, 7.4) 10.7 (9.8, 11.6) D (n=13,634) 58.6 (57.8, 59.5) 14.4 (13.8, 15.0) 10.4 (9.9, 10.9) 32.8 (32.0, 33.6) 25.7 (24.9, 26.4) 9.6 (9.1, 10.1) 4.9 (4.6, 5.3) 10.0 (9.5, 10.6) 3.3 (3.0, 3.6) F (n=8,739) 60.9 (59.9, 62.0) 11.7 (11.1, 12.4) 10.6 (10.0, 11.3) 36.5 (35.5, 37.6) 30.3 (29.4, 31.3) 11.7 (11.0, 12.4) 8.5 (7.9, 9.1) 12.3 (11.6, 13.0) 1.3 (1.0, 1.5) G (n=3,526) 53.0 (51.4, 54.6) 13.6 (12.5, 14.8) 9.4 (8.5, 10.5) 32.6 (31.1, 34.2) 24.0 (22.6, 25.4) 9.6 (8.7, 10.6) 5.8 (5.1, 6.6) 13.4 (12.3, 14.6) H (n=7,714) 55.8 (54.7, 56.9) 3.8 (3.4, 4.3) 8.7 (8.1, 9.3) 35.4 (34.4, 36.5) 27.7 (26.7, 28.7) 11.6 (10.9, 12.3) 8.1 (7.5, 8.7) 9.7 (9.0, 10.4) J (n=6,873) 57.3 (56.2, 58.5) 13.3 (12.5, 14.1) 4.3 (3.9, 4.8) 31.7 (30.6, 32.8) 24.9 (23.9, 25.9) 6.7 (6.1, 7.3) 4.2 (3.7, 4.7) 10.8 (10.1, 11.6) 2.5 (2.1, 2.9) K (n=8,819) 55.3 (54.3, 56.4) 8.8 (8.2, 9.4) 10.4 (9.8, 11.1) 34.0 (33.0, 35.0) 26.6 (25.7, 27.6) 9.9 (9.3, 10.5) 7.2 (6.7, 7.8) 11.9 (11.2, 12.6) 6.8 (6.2, 7.3) L (n=7,298) 57.7 (56.5, 58.9) 10.7 (10.0, 11.4) 34.9 (33.8, 36.0) 27.8 (26.7, 28.9) 11.9 (11.2, 12.7) 8.7 (8.1, 9.5) 13.0 (12.2, 13.8) 6.4 (5.9, 7.0) M (n=808) 60.4 (57.0, 63.7) 17.9 (15.5, 20.7) 11.8 (9.7, 14.2) 34.9 (31.7, 38.2) 27.4 (24.5, 30.6) 10.9 (8.9, 13.3) 6.9 (5.4, 8.9) 14.5 (12.3, 17.1) 7.4 (5.8, 9.4) N (n=2,888) 60.8 (59.0, 62.6) 10.0 (9.0, 11.2) 7.6 (6.6, 8.7) 32.0 (30.3, 33.7) 25.6 (24.0, 27.2) 6.6 (5.8, 7.6) 4.1 (3.4, 4.9) 9.3 (8.3, 10.4) 2.9 (2.4, 3.6) P (n=3,022) 57.2 (55.4, 59.0) 11.9 (10.8, 13.1) 34.5 (32.8, 36.2) 28.5 (26.9, 30.1) 12.9 (11.8, 14.2) 9.2 (8.2, 10.3) 12.9 (11.8, 14.2) 1.4 (1.1, 1.9) R (137) 59.9 (51.5, 67.7) 9.0 (5.2, 15.0) 30.6 (23.4, 38.8) 23.9 (17.5, 31.8) 6.0 (3.1, 11.3) 3.7 (1.6, 8.4) 7.5 (4.1, 13.2) 5.1 (2.5, 10.2) S (13,832) 58.5 (57.7, 59.3) 13.9 (13.3, 14.5) 8.4 (8.0, 8.9) 34.1 (33.3, 34.9) 27.2 (26.5, 28.0) 9.2 (8.7, 9.7) 6.4 (6.0, 6.8) 10.5 (10.0, 11.0) 4.7 (4.3, 5.1) T (n=124) 65.3 (56.6, 73.1) 21.8 (15.4, 29.8) 8.9 (5.0, 15.2) 39.5 (31.4, 48.3) 33.9 (26.1, 42.6) 8.1 (4.4, 14.2) 6.5 (3.3, 12.2) 12.1 (7.5, 19.0) 2.4 (0.8, 6.9) All-Wales: Resistance rates 57.9 (57.6, 58.3) 12.3 (12.1, 12.5) 9.3 (9.1, 9.5) 34.0 (33.7, 34.3) 27.0 (26.7, 27.3) 9.9 (9.7, 10.1) 6.6 (6.5, 6.8) 11.1 (10.9, 11.3) 4.0 (3.9, 4.1) All-Wales: Number of isolates 84,120 77,682 81,777 84,163 83,442 84,845 83,304 84,171 69,237 Key: AMO = amoxicillin, COA = co-amoxiclav, 1GC = first generation cephalosporin, TRI = trimethoprim, AMO/TRI = co-resiatnce to amoxicillin and trimethoprim FQ = ciprofloxacin &/or levofloaxcin, or norfloxacin, AMO/TRI/FQ = co-resistance to amoxicillin, trimethoprim and a fluroquinolone, NIT = nitrofurantoin, CPD = cefpodixime. Note: The range of resistance is outlined with boxes e.g. the range of resistance to amoxicillin was 53.0% - 65.2%; individual hospital rates statistically higher than the All-Wales rate are highlighted in colour. In 2012, a number of local communities had resistance rates for urinary coliforms that were statistically higher than the All-Wales rate; the most notable were the communities served by Princess of Wales (B), UHW (F), and Ysbyty Glan Clwyd (L). 32

Table 19: Hospital Out-Patient Urinary Coliforms TABLE 19: Out Patient Urinary Coliforms (including E.coli and Proteus spp. ) Resistance rates including (95% Confidence Intervals) Duplicate Cut Off: 91 days Time period: 1 January - 31 December 2012 Location Code AMO (95% CI) COA (95% CI) IGC (95% CI) TRI (95% CI) AMO/TRI (95% CI) FQ (95% CI) AMO/TRI/FQ(95% CI) NIT (95% CI) CPD (95% CI) A (n=93) 54.7 (44.7, 64.4) 7.5 (3.7, 14.7) 7.5 (3.7, 14.7) 23.4 (16.0, 32.9) 18.1 (11.6, 27.1) 7.4 (3.7, 14.6) 4.3 (1.7, 10.4) 10.6 (5.9, 18.5) 3.2 (1.1, 9.1) B (n=410) 58.6 (53.8, 63.3) 8.5 (6.2, 11.6) 7.8 (5.6, 10.8) 27.0 (22.9, 31.5) 22.1 (18.4, 26.4) 8.5 (6.2, 11.6) 6.3 (4.4, 9.1) 10.2 (7.6, 13.5) 4.1 (2.6, 6.5) C (n=182) 53.8 (47.8, 59.8) 10.0 (6.9, 14.2) 25.6 (20.7, 31.2) 21.5 (17.0, 26.9) 5.7 (3.5, 9.2) 4.6 (2.7, 7.9) 9.9 (6.9, 14.1) D (n=762) 55.4 (51.8, 58.9) 14.8 (12.5, 17.5) 11.8 (9.7, 14.3) 24.0 (21.0, 27.3) 17.3 (14.7, 20.2) 10.0 (8.1, 12.3) 2.7 (1.7, 4.1) 10.7 (8.6, 13.1) 2.7 (1.7, 4.2) E (n=359) 62.9 (57.8, 67.7) 17.7 (14.1, 22.0) 12.5 (9.5, 16.4) 32.6 (27.9, 37.6) 25.6 (21.4, 30.4) 14.1 (10.9, 18.1) 6.7 (4.5, 9.8) 10.6 (7.8, 14.2) 7.0 (4.8, 10.1) F (n=841) 67.9 (64.8, 70.9) 17.5 (15.1, 20.2) 16.9 (14.5, 19.6) 41.0 (37.8, 44.2) 35.4 (32.3, 38.6) 18.2 (15.8, 20.9) 14.1 (12.0, 16.6) 15.0 (12.8, 17.5) 2.0 (1.3, 3.3) G (n=223) 50.6 (45.1, 56.1) 10.6 (7.6, 14.5) 33.3 (28.3, 38.7) 21.8 (17.6, 26.7) 11.5 (8.5, 15.6) 8.0 (5.5, 11.6) 11.9 (8.7, 15.9) H (n=560) 53.9 (49.8, 58.0) 2.6 (1.6, 4.4) 7.0 (5.1, 9.4) 26.8 (23.3, 30.6) 20.8 (17.6, 24.3) 8.4 (6.4, 11.0) 5.7 (4.1, 8.0) 8.0 (6.1, 10.6) J (n=321) 63.0 (58.0, 67.8) 14.4 (11.2, 18.4) 6.9 (4.6, 10.2) 24.5 (20.4, 29.2) 21.3 (17.4, 25.7) 7.3 (5.1, 10.5) 3.5 (2.1, 6.0) 10.4 (7.7, 13.9) 4.4 (2.8, 7.1) K n=363) 58.1 (53.3, 62.8) 9.7 (7.2, 12.9) 10.2 (7.5, 13.7) 28.6 (24.5, 33.2) 23.8 (19.9, 28.1) 10.2 (7.6, 13.5) 7.3 (5.1, 10.2) 11.6 (8.9, 15.1) 6.1 (4.1, 8.8) L (n=935) 56.8 (53.6, 59.9) 13.9 (11.8, 16.3) 28.0 (25.3, 31.0) 22.6 (20.1, 25.4) 10.8 (9.0, 12.9) 8.5 (6.9, 10.4) 16.2 (14.0, 18.7) 7.8 (6.3, 9.7) M (n=287) 56.8 (51.0, 62.4) 19.2 (15.0, 24.1) 11.5 (8.3, 15.7) 28.5 (23.6, 34.0) 23.9 (19.3, 29.2) 6.3 (4.0, 9.8) 4.6 (2.7, 7.7) 12.0 (8.7, 16.3) 7.7 (5.2, 11.4) N (n=135) 56.3 (49.7, 62.7) 8.6 (5.5, 13.0) 30.6 (24.9, 37.0) 28.4 (22.9, 34.6) 5.9 (3.5, 9.8) 4.1 (2.1, 7.5) 7.7 (4.8, 11.9) 2.3 (1.0, 5.2) P (n=252) 49.4 (43.4, 55.5) 11.2 (7.9, 15.6) 7.1 (4.6, 11.0) 27.4 (22.3, 33.1) 20.5 (16.0, 25.8) 9.7 (6.6, 13.9) 5.4 (3.2, 8.9) 11.6 (8.2, 16.1) 0.0 (0.0, 1.5) Q (n=43) 49.1 (36.4, 61.9) 18.2 (10.2, 30.3) 36.4 (24.9, 49.6) 25.5 (15.8, 38.3) 10.9 (5.1, 21.8) 9.1 (3.9, 19.6) 18.2 (10.2, 30.3) 1.9 (0.3, 10.1) R (n=139) 54.1 (46.0, 62.0) 12.4 (8.0, 18.8) 3.6 (1.5, 8.1) 25.7 (19.3, 33.4) 16.0 (10.9, 22.8) 3.4 (1.5, 7.8) 2.8 (1.1, 6.9) 13.9 (9.2, 20.5) 2.9 (1.1, 7.1) S (n=160) 62.3 (54.5, 69.4) 15.0 (10.3, 21.3) 6.3 (3.4, 11.1) 33.8 (26.9, 41.4) 30.8 (24.2, 38.4) 6.3 (3.4, 11.1) 5.7 (3.0, 10.4) 5.0 (2.6, 9.6) 3.1 (1.3, 7.1) T (n=142) 58.5 (50.2, 66.2) 16.2 (11.0, 23.1) 6.3 (3.4, 11.6) 24.6 (18.3, 32.3) 21.1 (15.2, 28.6) 9.2 (5.4, 15.0) 4.2 (2.0, 8.9) 9.2 (5.4, 15.0) 2.8 (1.1, 7.0) All-Wales: Resistance rates 58.3 (57.1, 59.5) 13.6 (12.7, 14.4) 10.8 (10.1, 11.6) 29.8 (28.8, 30.9) 24.1 (23.1, 25.1) 10.5 (9.8, 11.2) 7.0 (6.4, 7.6) 11.9 (11.2, 12.7) 4.3 (3.8, 4.9) All-Wales: Number of isolates 6,853 6,155 6,376 6,806 6,794 6,857 6,792 6,807 5,672 Key: AMO = amoxicillin, COA = co-amoxiclav, 1GC = first generation cephalosporin, TRI = trimethoprim, AMO/TRI = co-resiatnce to amoxicillin and trimethoprim FQ = ciprofloxacin &/or levofloaxcin, or norfloxacin, AMO/TRI/FQ = co-resistance to amoxicillin, trimethoprim and a fluroquinolone, NIT = nitrofurantoin, CPD = cefpodixime.. Note: In 2012, the All-Wales resistance rates for out-patients urinary coliforms were comparable to the rates for community urinary coliforms for amoxicillin, co-amoxiclav, first generation cephalosporins, fluoroquinolones and nitrofurantoin (Tables 18 & 19). Trimethoprim resistance rates were statistically higher in community urinary coliforms. The resistance rates for out-patient urinary coliforms for UHW (F) were statistically higher than the All-Wales rate for most of the agents listed, with notably high resistance to amoxicillin, first generation cephalosporins, trimethoprim and fluoroquinolones, and a co-resistance rate of 14.1% to AMO/TRI/FQ. 33

Table 20: Hospital In-Patient Urinary Coliforms TABLE 20: In Patient Urinary Coliforms (including E.coli and Proteus spp. ) Resistance rates including (95% Confidence Intervals) Duplicate Cut Off: 14days Time period: 1 January - 31 December 2012 Location Code AMO (95% CI) COA (95% CI) IGC (95% CI) TRI (95% CI) AMO/TRI (95% CI) FQ (95% CI) AMO/TRI/FQ(95% CI) NIT (95% CI) CPD (95% CI) A (n=274) 57.9 (51.9, 63.6) 15.0 (11.2, 19.7) 33.8 (28.5, 39.6) 23.9 (19.2, 29.3) 8.8 (6.0, 12.7) 6.6 (4.2, 10.2) 12.8 (9.4, 17.3) 4.1 (2.3, 7.2) B (n=626) 61.3 (57.5, 65.1) 10.7 (8.5, 13.4) 11.0 (8.8, 13.7) 34.7 (31.0, 38.5) 28.0 (24.6, 31.6) 12.6 (10.2, 15.5) 9.4 (7.4, 12.0) 16.3 (13.6, 19.4) 7.0 (5.3, 9.3) C (n=805) 66.6 (63.3, 69.8) 16.9 (14.5, 19.6) 35.4 (32.2, 38.8) 29.6 (26.5, 32.8) 13.3 (11.1, 15.8) 11.1 (9.1, 13.5) 15.4 (13.1, 18.1) D (n=1,437) 64.7 (62.2, 67.1) 18.1 (16.2, 20.2) 14.6 (12.9, 16.5) 26.6 (24.3, 29.1) 22.2 (20.0, 24.6) 11.5 (10.0, 13.3) 4.4 (3.4, 5.7) 11.0 (9.4, 12.8) 2.4 (1.7, 3.4) E (n=1,085) 67.0 (64.2, 69.7) 22.3 (19.9, 24.9) 15.4 (13.4, 17.7) 37.0 (34.2, 39.9) 31.6 (28.9, 34.4) 14.6 (12.6, 16.8) 9.7 (8.0, 11.6) 16.2 (14.1, 18.5) 8.7 (7.1, 10.5) F (n=1,854) 69.2 (67.1, 71.3) 19.6 (17.9, 21.5) 39.9 (37.7, 42.2) 33.5 (31.4, 35.7) 16.1 (14.5, 17.8) 11.4 (10.0, 12.9) 19.3 (17.5, 21.1) 2.1 (1.6, 3.0) G (n=510) 58.0 (53.7, 62.2) 15.7 (12.8, 19.1) 36.7 (32.6, 40.9) 26.3 (22.6, 30.3) 10.6 (8.2, 13.6) 6.9 (5.0, 9.4) 17.8 (14.8, 21.4) H (n=1,228) 66.2 (63.5, 68.8) 6.3 (5.0, 8.0) 15.9 (14.0, 18.1) 39.9 (37.2, 42.7) 33.4 (30.8, 36.1) 19.0 (16.9, 21.3) 14.5 (12.7, 16.6) 11.9 (10.2, 13.8) J (n=716) 65.6 (62.0, 69.0) 19.0 (16.3, 22.1) 33.1 (29.7, 36.6) 27.0 (23.9, 30.4) 8.8 (7.0, 11.1) 6.2 (4.7, 8.3) 13.3 (11.0, 16.0) 4.3 (3.0, 6.0) K (n=1,075) 64.2 (61.3, 67.0) 13.9 (11.9, 16.1) 37.9 (35.0, 40.8) 32.2 (29.5, 35.1) 12.3 (10.5, 14.4) 9.1 (7.5, 11.0) 17.0 (14.9, 19.4) 9.1 (7.5, 11.0) L (n=1,340) 16.6 (14.7, 18.7) 37.8 (35.2, 40.4) 17.5 (15.6, 19.7) 15.9 (14.0, 18.0) 12.3 (10.7, 14.2) M (n=693) 62.6 (59.0, 66.1) 17.9 (15.2, 20.9) 12.0 (9.8, 14.6) 32.9 (29.5, 36.4) 26.3 (23.2, 29.7) 10.1 (8.1, 12.6) 7.2 (5.5, 9.4) 15.8 (13.2, 18.7) 8.3 (6.5, 10.7) N (n=547) 63.4 (59.2, 67.3) 12.1 (9.6, 15.1) 28.4 (24.8, 32.4) 25.0 (21.5, 28.8) 11.2 (8.8, 14.1) 7.6 (5.6, 10.1) 11.0 (8.6, 13.9) 3.7 (2.4, 5.7) P (n=755) 71.7 (68.3, 74.8) 21.2 (18.4, 24.2) 46.7 (43.1, 50.3) 41.5 (38.0, 45.1) 20.9 (18.2, 24.0) 17.8 (15.2, 20.7) 17.4 (14.8, 20.2) 2.4 (1.5, 3.9) R (n=231) 63.6 (57.3, 69.6) 20.4 (15.7, 26.1) 31.1 (25.5, 37.4) 26.8 (21.4, 32.9) 10.0 (6.8, 14.6) 7.5 (4.7, 11.6) 12.3 (8.6, 17.2) 4.9 (2.8, 8.6) S (n=387) 67.4 (62.6, 71.9) 21.7 (17.9, 26.1) 17.7 (14.2, 21.8) 41.7 (36.8, 46.7) 36.7 (32.1, 41.6) 16.8 (13.4, 20.8) 14.3 (11.2, 18.2) 12.8 (9.8, 16.5) 12.2 (9.3, 15.9) T (n=251) 65.7 (59.7, 71.3) 19.6 (15.2, 25.0) 10.4 (7.2, 14.9) 41.4 (35.4, 47.6) 34.1 (28.5, 40.2) 15.9 (11.9, 21.0) 12.0 (8.6, 16.7) 12.4 (8.9, 17.1) 8.1 (5.3, 12.1) W (n=131) 77.1 (69.2, 83.5) 26.7 (19.9, 34.9) 58.0 (49.5, 66.1) 51.9 (43.4, 60.3) 28.2 (21.2, 36.5) 23.7 (17.2, 31.6) 29.8 (22.6, 38.1) 2.9 (1.0, 8.1) All-Wales: Resistance rates 66.2 (65.4, 67.0) 18.0 (17.4, 18.7) 17.8 (17.0, 18.6) 36.7 (35.9, 37.5) 31.3 (30.5, 32.1) 14.4 (13.9, 15.0) 10.8 (10.3, 11.3 15.4 (14.8, 16.0) 6.2 (5.8, 6.7) All-Wales: Number of isolates 13,155 12,862 8,890 13,977 12,973 14,144 12,968 13,980 11,329 Key: AMO = amoxicillin, COA = co-amoxiclav, 1GC = first generation cephalosporin, TRI = trimethoprim, AMO/TRI = co-resiatnce to amoxicillin and trimethoprim FQ = ciprofloxacin &/or levofloaxcin, or norfloxacin, AMO/TRI/FQ = co-resistance to amoxicillin, trimethoprim and a fluroquinolone, NIT = nitrofurantoin, CPD = cefpodixime.. In 2012, the All-Wales resistance rates for in-patients urinary coliforms were statistically higher for all the agents listed than those for community or out-patients (Tables 18, 19 & 20). In 2012, a number of hospitals had resistance rates for urinary coliforms that were statistically higher than the All-Wales rate; the most notable were Llandough (P) and West Wing CRI (W). Resistance rates for West Wing CRI (W) were high, especially to agents such as trimethoprim (TRI): 58.0% (49.5, 66.1), fluoroquinolones: 28.2% (21.2, 36.5), and with co-resistance to amoxicillin, trimethoprim and fluoroquinolones of 23.7%. West Wing is a long-term elderly care unit; the proportion of patients that are catheterized is higher than the other hospitals included in this report, the proportion of patients receiving long-term medical prophylaxis for recurrent UTI is also higher, and both of these factors may influence resistance. West Wing is included in this report to demonstrate this point. 34

Resistance (%) Community Urinary Coliforms (n=84,947 in 2012) The All-Wales pattern of antimicrobial resistance for community urinary coliforms is shown in Figure 16 & Table 18. There has been a statistically significant increase in the resistance rate for co-amoxiclav year on year between 2005 & 2011 but in 2012 the rate decreased probably due to a laboratory artefact (see Summary page 4). 70 65 60 55 50 45 40 35 30 25 20 15 10 5 0 1GC AMO AMO/TRI AMO/TRI/FQ COA CPD FQ NIT TRI 2005 7.1 51.2 21.1 4.3 9.4 3.7 5.8 11.2 26.8 2006 7.9 52.5 23.0 5.3 10.8 3.9 7.0 11.6 29.0 2007 9.4 53.1 24.1 5.9 12.3 4.4 8.0 11.3 30.5 2008 9.8 56.0 25.0 6.6 12.9 4.7 9.1 11.1 30.7 2009 10.2 57.0 25.2 6.7 14.0 4.7 9.5 10.8 30.9 2010 10.1 57.3 25.6 6.5 14.6 4.8 9.7 10.3 31.5 2011 9.8 58.4 26.3 6.6 17.2 4.3 9.9 10.7 32.5 2012 9.3 57.9 27.0 6.6 12.3 4.0 9.9 11.1 34.0 Figure 16: All-Wales antimicrobial resistance rates for coliforms from community urine samples (2005 to 2012) The high rates of resistance, notably for trimethoprim, may reflect an element of selective testing within the community. The true rate of resistance to trimethoprim 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 most of these patients. 35

Resistance (%) Out-patient Urinary Coliforms (n=6,865 in 2012) The All-Wales pattern of antimicrobial resistance for out-patient urinary coliforms is shown in Figure 17 & Table 19. There has been a general levelling off of resistance rates for urinary coliforms from out-patient samples between 2010-2012. There was a statistically significant decrease in co-amoxiclav resistance rates, due to reasons previously described. 70 65 60 55 50 45 40 35 30 25 20 15 10 5 0 1GC AMO AMO/TRI AMO/TRI/FQ COA CPD FQ NIT TRI 2005 8.9 51.1 20.2 5.7 10.2 5.9 7.6 11.9 26.2 2006 9.4 53.9 21.5 6.6 12.5 6.1 8.7 13.4 27.9 2007 12.2 55.2 24.4 7.6 15.8 7.2 10.4 14.6 30.5 2008 11.8 56.8 23.9 8.2 14.7 6.9 11.4 13.8 29.3 2009 10.9 57.3 23.3 6.1 14.7 5.1 9.2 12.3 28.6 2010 10.6 57.7 23.9 6.6 15.2 5.0 10.2 11.0 29.7 2011 10.6 58.5 24.5 7.1 17.1 4.7 11.0 11.6 30.1 2012 10.8 58.3 24.1 7.0 13.6 4.3 10.5 11.9 29.8 Figure 17: All-Wales antimicrobial resistance rates for coliforms from out-patient urine samples (2005 to 2012) 36

Resistance (%) In-patient Urinary Coliforms (n=14,164 in 2012) The All-Wales pattern of antimicrobial resistance for in-patient urinary coliforms is shown in Figure 18 & Table 20. There was no significant difference in resistance rates for urinary coliforms from in-patient samples between 2011 and 2012, except for co-amoxiclav which decreased due to reasons previously described. 70 65 60 55 50 45 40 35 30 25 20 15 10 5 0 1GC AMO AMO/TRI AMO/TRI/FQ COA CPD FQ NIT TRI 2005 12.7 57.4 24.0 9.1 15.8 8.2 11.8 16.8 29.1 2006 15.1 59.6 27.3 11.4 18.6 10.5 14.0 18.3 32.3 2007 16.9 61.0 29.0 12.5 21.8 11.5 15.6 17.6 33.7 2008 16.4 63.3 29.4 12.4 21.5 10.1 15.5 17.6 34.2 2009 16.3 65.3 29.4 11.8 21.9 9.0 15.2 17.2 33.9 2010 16.2 65.3 29.3 10.7 21.7 7.9 14.5 16.6 34.1 2011 17.9 66.7 30.9 11.3 24.4 6.9 15.5 15.4 35.7 2012 17.8 66.2 31.3 10.8 18.0 6.2 14.4 15.4 36.7 Figure 18: All-Wales antimicrobial resistance rates for coliforms from in-patient urine samples (2005 to 2012) 37

Section 4.3: Antimicrobial resistance rates for Staphylococcus aureus The data in this section is presented to reflect the antimicrobial susceptibility of organisms causing skin and soft tissue infections occurring in the community, and is based on the specimen description wound swab. However, it should be noted that there is a significant sampling bias in this data. Royal Gwent and Nevill Hall are not included in the MSSA or MRSA data sets as they do not use the specimen type description wound swab in their laboratory management systems. 38

Tables 21 & 22: Meticillin Sensitive Staphylococcus aureus (MSSA) from community and in-patient wound swab TABLE 21: Meticillin Sensitive Staphylococcus aureus from community wound swabs Resistance rates including (95% Confidence Intervals) Duplicate Cut Off: 91 days Time period: 1 January - 31 December 2012 Location Code ERY (95% CI) FUS (95% CI) GEN (95% CI) PEN (95% CI) TET (95% CI) A (n=587) 10.6 (8.3, 13.3) 92.2 (89.7, 94.1) 5.5 (3.9, 7.6) B (n=52) 5.8 (2.0, 15.6) 11.5 (5.4, 23.0) 86.5 (74.7, 93.3) 0.0 (0.0, 6.9) C (n=734) 79.5 (76.4, 82.3) 2.5 (1.6, 3.9) F (n=1,427) 15.1 (13.3, 17.0) 13.3 (11.6, 15.1) (0.3, 1.1) 4.5 (3.5, 5.7) G (n=543) 15.1 (12.3, 18.4) 86.0 (82.8, 88.7) 4.6 (3.2, 6.7) H (n=1,230) 16.1 (14.2, 18.3) 16.1 (14.1, 18.2) J (n=1,175) 12.6 (10.8, 14.6) 10.6 84.3 (82.1, 86.3) 4.0 (3.0, 5.3) K (n=1,003) 12.6 (10.7, 14.8) 15.8 (13.6, 18.1) 0.3 (0.1, 0.9) 78.9 (76.2, 81.3) 5.4 (4.1, 7.0) L (n=878) 14.5 (12.3, 17.0) 15.5 (13.3, 18.1) 0.5 (0.2, 1.2) 7.0 (5.5, 8.8) P (n=44) 18.2 (9.5, 32.0) 11.4 (5.0, 24.0) 0.0 (0.0, 8.0) 4.5 (1.3, 15.1) R (n=29) 10.3 (3.6, 26.4) 89.7 (73.6, 96.4) 10.3 (3.6, 26.4) S (n=3,141) 11.9 (10.8, 13.1) 17.6 (16.3, 19.0) 0.3 (0.2, 0.6) 80.2 (78.8, 81.6) 4.2 (3.6, 5.0) T (n=24) 4.2 (0.7, 20.2) 12.5 (4.3, 31.0) 0.0 (0.0, 13.8) 70.8 (50.8, 85.1) 4.2 (0.7, 20.2) All-Wales: Resistance rates 13.3 (12.7, 14.0) 15.50067 (14.8, 16.3) 0.5 (0.3, 0.6) 82.1 (81.2, 83.0) 4.7 (4.3, 5.2) All-Wales: Number of isolates 10,137 8,948 6,968 7,324 9,666 TABLE 22: Meticillin Sensitive Staphylococcus aureus from In-Patient wound swabs Resistance rates including (95% Confidence Intervals) Duplicate Cut Off: 14 days Time period: 1 January - 31 December 2012 Location Code ERY (95% CI) FUS (95% CI) GEN (95% CI) PEN (95% CI) TET (95% CI) A (n=67) 16.7 (9.6, 27.4) 90.8 (81.3, 95.7) 4.5 (1.6, 12.5) B (n=150) 10.0 (6.2, 15.8) 8.7 (5.2, 14.4) 84.7 (78.0, 89.6) 2.0 (0.7, 5.7) C (n=200) 75.8 (69.3, 81.2) 2.5 (1.1, 5.7) E (n=501) 9.2 (7.0, 12.1) 13.4 (10.7, 16.7) 1.4 (0.7, 2.9) 83.6 (80.1, 86.6) 4.4 (2.9, 6.6) F (n=537) 13.0 (10.4, 16.1) 9.9 (7.7, 12.7) 0.6 (0.2, 1.6) 4.5 (3.0, 6.6) G (n=132) 8.3 (4.7, 14.3) 90.9 (84.8, 94.7) 3.8 (1.6, 8.6) H (n=229) 13.2 (9.4, 18.2) 12.2 (8.6, 17.1) J (n=141) 17.9 (12.4, 25.0) 89.3 (83.1, 93.4) 5.7 (2.9, 10.9) K (n=166) 12.7 (8.4, 18.6) 12.7 (8.4, 18.6) 0.0 (0.0, 2.3) 80.7 (74.1, 86.0) 6.0 (3.3, 10.7) L (n=239) 16.3 (12.2, 21.5) 23.0 (18.1, 28.8) 0.0 (0.0, 1.6) 7.6 (4.8, 11.6) P (n=134) 15.7 (10.5, 22.8) 20.9 (14.9, 28.5) 5.2 (2.6, 10.4) 6.0 (3.1, 11.4) Q (n=30) 16.7 (7.3, 33.6) 13.3 (5.3, 29.7) 0.0 (0.0, 11.4) 0.0 (0.0, 11.4) R (n=26) 23.1 (11.0, 42.1) 88.5 (71.0, 96.0) 15.4 (6.1, 33.5) S (n=115) 14.9 (9.5, 22.6) 14.9 (9.5, 22.6) 0.9 (0.2, 4.8) 86.0 (78.4, 91.2) 6.1 (3.0, 12.1) T (n=48) 14.6 (7.2, 27.2) 12.5 (5.9, 24.7) 0.0 (0.0, 7.4) 89.6 (77.8, 95.5) 4.2 (1.2, 14.0) All-Wales: Resistance rates 13.0 (11.8, 14.4) 13.8 (12.5, 15.2) 1.0 (0.7, 1.6) 84.50704 (82.6, 86.2) 4.8 (4.0, 5.7) All-Wales: Number of isolates 2,553 2,363 1,946 1,562 2,511 Key: ERY = erythromycin, FUS = fusidic acid, GEN = gentamicin, PEN = penicillin, TET = tetracycline 39

Table 23: Meticillin Sensitive Staphylococcus aureus (MSSA) from out-patient wound swabs TABLE 23: Meticillin Sensitive Staphylococcus aureus from Out-Patient wound swabs Resistance rates including (95% Confidence Intervals) Duplicate Cut Off: 14 days Time period: 1 January - 31 December 2012 Location Code ERY (95% CI) FUS (95% CI) GEN (95% CI) PEN (95% CI) TET (95% CI) A (n=15) 6.7 (1.2, 29.8) 33.3 (12.1, 64.6) 93.3 (70.2, 98.8) 0.0 (0.0, 20.4) B (n=103) 20.4 (13.7, 29.2) 13.7 (8.4, 21.7) 81.6 (73.0, 87.9) 5.8 (2.7, 12.1) C (n=98) 84.7 (76.3, 90.5) 3.1 (1.0, 8.6) E (n=541) 9.8 (7.6, 12.6) 12.6 (10.0, 15.6) 1.1 (0.5, 2.4) 83.5 (80.2, 86.4) 5.0 (3.5, 7.2) F (n=188) 13.3 (9.2, 18.9) 14.4 (10.1, 20.1) 1.6 (0.5, 4.6) 4.3 (2.2, 8.2) G (n=45) 11.1 (4.8, 23.5) 91.1 (79.3, 96.5) 11.1 (4.8, 23.5) H (n=154) 17.5 (12.3, 24.3) 28.6 (22.0, 36.2) J (n=67) 13.4 (7.2, 23.6) 7.4 (2.1, 23.4) 92.5 (83.7, 96.8) 3.0 (0.8, 10.2) K (n=109) 11.9 (7.1, 19.3) 21.1 (14.5, 29.7) 0.0 (0.0, 3.4) 84.4 (76.4, 90.0) 9.2 (5.1, 16.1) L (n=163) 15.3 (10.6, 21.7) 25.2 (19.1, 32.3) 0.0 (0.0, 2.3) 7.5 (4.3, 12.6) P (n=20) 15.0 (5.2, 36.0) 15.0 (5.2, 36.0) 0.0 (0.0, 16.1) 5.0 (0.9, 23.6) Q (n=29) 17.2 (7.6, 34.5) 6.9 (1.9, 22.0) 0.0 (0.0, 11.7) 0.0 (0.0, 11.7) R (n=43) 14.3 (6.7, 27.8) 20.8 (9.2, 40.5) 90.5 (77.9, 96.2) 14.3 (6.7, 27.8) S (n=125) 16.8 (11.3, 24.3) 23.2 (16.7, 31.3) 1.6 (0.4, 5.6) 81.6 (73.9, 87.4) 7.2 (3.8, 13.1) T (n=28) 10.7 (3.7, 27.2) 17.9 (7.9, 35.6) 0.0 (0.0, 12.5) 96.4 (82.3, 99.4) 3.6 (0.6, 17.7) All-Wales: Resistance rates 13.5 (11.9, 15.2) 17.7 (15.8, 19.6) 0.8 (0.5, 1.5) 84.9789 (82.8, 86.9) 6.0 (4.9, 7.2) All-Wales: Number of isolates 1,655 1,563 1,297 1,185 1,594 Key: ERY = erythromycin, FUS = fusidic acid, GEN = gentamicin, PEN = penicillin, TET = tetracycline Note: The range of resistance is outlined with boxes e.g. the range of resistance to erythromycin was 6.7% - 17.5%; individual hospital rates statistically higher than the All-Wales rate are highlighted in colour. 40

2005 2012 Resistance (%) MSSA ( n=15,374 in 2012) Community MSSA (n=10,877 in 2012) The All-Wales pattern of antimicrobial resistance for MSSA from community wound swabs are shown in Figure 19 and Table 21 with no statistically significant difference in the resistance rates for any of the agents listed between 2005 and 2012, but a notable increase in trend for erythromycin and fusidic acid resistance. 100 90 80 70 60 50 40 30 20 10 0 ERY FUS GEN PEN Figure 19: All-Wales antimicrobial resistance rates for MSSA from community Wound swabs (2005 to 2012) In 2012, the All-Wales resistance rates for community, out-patients and in-patients MSSA were comparable for most of the antimicrobials listed: erythromycin (ERY), gentamicin (GEN), mupirocin (MUP), penicillin (PEN) and tetracycline (TET) see Tables 21, 22 and 23. At different times in the eight year period 2005 to 2012, there were increases in resistance to different agents in different geographical areas, but there was no set pattern of increasing or high resistance in any particular community or hospital, and this probably reflects the varying presence of epidemic strains. Resistance to fusidic acid (FUS) and tetracycline (TET) was higher for outpatient MSSA compared to in-patient and community rates. Vancomycin resistance remained undetected in MSSA between 2005 & 2012. 41

Tables 24 & 25: Meticillin Resistant Staphylococcus aureus (MRSA) from community and in-patient wound swabs TABLE 24: Meticillin Resistant Staphylococcus aureus from community wound swabs Resistance rates including (95% Confidence Intervals) Duplicate Cut Off: 91 days Time period: 1 January - 31 December 2012 Location Code ERY (95% CI) FQ (95% CI) FUS (95% CI) GEN (95% CI) LZD (95% CI) MUP (95% CI) RIF (95% CI) TET (95% CI) VAN (95% CI) A (n=53) 64.2 (50.7, 75.7) 11.5 (5.4, 23.0) 13.2 (6.5, 24.8) C (n=95) 48.6 (37.2, 60.0) 2.1 (0.6, 7.4) 13.8 (8.3, 22.2) F (n=228) 63.2 (56.7, 69.2) 84.7 (78.9, 89.2) 11.5 (8.0, 16.3) 4.8 (2.7, 8.4) 0.5 (0.1, 3.0) 2.6 (1.1, 6.0) 3.7 (1.8, 7.4) 11.5 (7.9, 16.3) 0.0 (0.0, 2.0) G (n=47) 68.1 (53.8, 79.6) 2.6 (0.5, 13.5) 4.9 (1.3, 16.1) 2.1 (0.4, 11.1) H (n=179) 63.1 (55.9, 69.9) 45.8 (38.7, 53.1) 1.7 (0.6, 4.8) 0.0 (0.0, 2.1) 1.7 (0.6, 4.8) 0.0 (0.0, 2.1) 41.3 (34.4, 48.7) J (n=106) 63.7 (54.1, 72.4) 89.0 (80.9, 93.9) 5.5 (2.4, 12.2) 12.0 (6.8, 20.2) 0.0 (0.0, 4.1) 10.9 (6.2, 18.5) 2.3 (0.6, 8.0) 0.0 (0.0, 3.6) K (n=199) 65.3 (58.5, 71.6) 18.1 (13.4, 24.0) 1.5 (0.5, 4.3) 17.6 (12.9, 23.5) 0.0 (0.0, 1.9) L (n=253) 68.4 (62.4, 73.8) 36.4 (30.7, 42.5) 0.8 (0.2, 2.8) 34.0 (28.4, 40.0) P (n=16) 66.7 (41.7, 84.8) 12.5 (3.5, 36.0) 18.8 (6.6, 43.0) 18.8 (6.6, 43.0) S (n=323) 59.1 (53.7, 64.4) 85.8 (81.5, 89.2) 18.3 (14.4, 22.8) 9.8 (6.8, 14.0) 0.0 (0.0, 1.2) 13.6 (10.2, 17.8) 0.3 (0.1, 1.8) 6.8 (4.6, 10.1) 0.0 (0.0, 1.3) All-Wales: Resistance rates 62.9 (60.4, 65.3) 87.2 (84.8, 89.2) 22.2 (20.1, 24.4) 4.6 (3.6, 5.8) 0.2 (0.1, 0.8) 6.6 (5.3, 8.2) 1.0 (0.6, 1.8) 17.9 (16.1, 19.9) 0.0 (0.0, 0.4) All-Wales: Number of isolates 1,485 898 1,445 1,378 904 1,136 1,111 1,508 971 Key: ERY = erythromycin, FQ = fluoroquinolone, FUS = fusidic acid, GEN = gentamicin, LZD = linezolid, MUP = mupirocin, RIF = rifampicin, TET = tetracycline TABLE 25: Meticillin Resistant Staphylococcus aureus from In-patient wound swabs Resistance rates including (95% Confidence Intervals) Duplicate Cut Off: 14 days Time period: 1 January - 31 December 2012 Location Code ERY (95% CI) FQ (95% CI) FUS (95% CI) GEN (95% CI) LZD (95% CI) MUP (95% CI) RIF (95% CI) TET (95% CI) VAN (95% CI) A (n=12) 66.7 (39.1, 86.2) 100 (72.2, 100) 0.0 (0.0, 27.8) 0.0 (0.0, 27.8) 0.0 (0.0, 27.8) 0.0 (0.0, 24.3) 0.0 (0.0, 24.3) B (n=32) 64.5 (46.9, 78.9) 93.1 (78.0, 98.1) 9.7 (3.3, 24.9) 0.0 (0.0, 11.7) 3.4 (0.6, 17.2) 0.0 (0.0, 11.7) 3.2 (0.6, 16.2) C (n=44) 72.4 (54.3, 85.3) 4.5 (1.3, 15.1) 16.3 (8.1, 30.0) E (n=78) 64.5 (53.3, 74.3) 94.7 (87.1, 97.9) 7.9 (3.7, 16.2) 19.7 (12.3, 30.0) 0.0 (0.0, 4.9) 28.0 (19.1, 39.0) 0.0 (0.0, 4.9) 1.3 (0.2, 7.1) 0.0 (0.0, 5.0) F (n=134) 73.9 (65.9, 80.6) 6.7 (3.6, 12.3) 5.3 (2.6, 10.5) 15.7 (10.5, 22.8) G (n=18) 66.7 (43.7, 83.7) 12.5 (3.5, 36.0) 11.8 (3.3, 34.3) H (n=94) 71.3 (61.4, 79.4) 37.2 (28.1, 47.3) 1.1 (0.2, 5.8) 0.0 (0.0, 3.9) 0.0 (0.0, 3.9) 1.1 (0.2, 5.8) 31.9 (23.4, 41.9) J (n=25) 79.2 (59.5, 90.8) 100 (84.5, 100) 4.8 (0.8, 22.7) 14.3 (5.0, 34.6) 0.0 (0.0, 15.5) 8.3 (2.3, 25.8) 0.0 (0.0, 15.5) 0.0 (0.0, 13.8) K (n=78) 66.7 (55.6, 76.1) 19.2 (12.0, 29.3) 1.3 (0.2, 6.9) 21.8 (14.1, 32.2) 0.0 (0.0, 4.7) L (n=111) 74.8 (66.0, 81.9) 30.6 (22.8, 39.7) 1.8 (0.5, 6.3) 30.6 (22.8, 39.7) P (n=37) 86.1 (71.3, 93.9) 8.3 (2.9, 21.8) 2.8 (0.5, 14.2) 22.2 (11.7, 38.1) S (n=18) 72.2 (49.1, 87.5) 100 (82.4, 100) 0.0 (0.0, 17.6) 27.8 (12.5, 50.9) 0.0 (0.0, 17.6) 38.9 (20.3, 61.4) 0.0 (0.0, 17.6) 0.0 (0.0, 17.6) 0.0 (0.0, 17.6) T (n=11) 50.0 (23.7, 76.3) 100 (72.2, 100) 30.0 (10.8, 60.3) 0.0 (0.0, 27.8) 0.0 (0.0, 27.8) 0.0 (0.0, 25.9) 0.0 (0.0, 27.8) 18.2 (5.1, 47.7) 0.0 (0.0, 27.8) All-Wales: Resistance rates 71.5 (68.1, 74.7) 92.1 (89.1, 94.3) 16.6 (14.0, 19.5) 5.9 (4.3, 7.9) 0.0 (0.0, 0.9) 8.4 (6.4, 11.1) 0.6 (0.2, 1.6) 17.2 (14.6, 20.1) 0.0 (0.0, 0.8) All-Wales: Number of isolates 709 429 699 665 441 545 541 723 458 Key: ERY = erythromycin, FQ = fluoroquinolone, FUS = fusidic acid, GEN = gentamicin, LZD = linezolid, MUP = mupirocin, RIF = rifampicin, TET = tetracycline 42

Table 26: Meticillin Resistant Staphylococcus aureus (MRSA) from out-patient wound swabs TABLE 26: Meticillin Resistant Staphylococcus aureus from Out-patient wound swabs Resistance rates including (95% Confidence Intervals) Duplicate Cut Off: 91 days Time period: 1 January - 31 December 2012 Location Code ERY (95% CI) FQ (95% CI) FUS (95% CI) GEN (95% CI) LZD (95% CI) MUP (95% CI) RIF (95% CI) TET (95% CI) VAN (95% CI) E (n=30) 69.0 (50.8, 82.7) 96.6 (82.8, 99.4) 13.8 (5.5, 30.6) 27.6 (14.7, 45.7) 0.0 (0.0, 11.7) 24.1 (12.2, 42.1) 0.0 (0.0, 11.7) 3.4 (0.6, 17.2) 0.0 (0.0, 12.1) F (n=29) 69.0 (50.8, 82.7) 82.6 (62.9, 93.0) 13.8 (5.5, 30.6) 3.4 (0.6, 17.2) 0.0 (0.0, 13.8) 4.2 (0.7, 20.2) 0.0 (0.0, 13.8) 24.1 (12.2, 42.1) 0.0 (0.0, 13.8) K (n=22) 68.2 (47.3, 83.6) 27.3 (13.2, 48.2) 0.0 (0.0, 14.9) 27.3 (13.2, 48.2) 0.0 (0.0, 14.9) L (n=28) 67.9 (49.3, 82.1) 53.6 (35.8, 70.5) 3.6 (0.6, 17.7) 35.7 (20.7, 54.2) All-Wales: Resistance rates 66.0 (58.3, 73.0) 86.9 (78.8, 92.2) 25.3 (19.0, 32.8) 7.6 (4.3, 13.2) 0.0 (0.0, 4.0) 10.2 (5.9, 16.9) 0.9 (0.2, 4.8) 19.6 (14.2, 26.5) 0.0 (0.0, 3.2) All-Wales: Number of isolates 156 99 150 144 92 118 115 158 175 Key: ERY = erythromycin, FQ = fluoroquinolone, FUS = fusidic acid, GEN = gentamicin, LZD = linezolid, MUP = mupirocin, RIF = rifampicin, TET = tetracycline There were no confirmed cases of vancomycin intermediate/resistant MRSA (VISA) between 2005 and 2012. 43

Resistance (%) MRSA (n=2,748 in 2012) Community MRSA (n=1,516 in 2012) The All-Wales pattern of antimicrobial resistance for MRSA from community wound swabs is shown in Figure 20 and Table 24, with no statistically significant changes in the resistance rates for any of the agents listed between 2011 and 2012, but with an increasing trend in resistance for fusidic acid, gentamicin, mupirocin and tetracycline. 100 90 80 70 60 50 40 30 20 10 0 ERY FQ FUS GEN LZD MUP RIF TET Figure 20: All-Wales antimicrobial resistance rates for MRSA from community Wound swabs (2005 to 2012) Locally, there was wide variability in resistance rates within Wales; with notably high rates in some areas e.g. fusidic acid and tetracycline resistance in communities served by the laboratories in Wrexham Maelor (H), and Ysbyty Glan Clwyd (L), see Table 24. Gentamicin and mupirocin resistance was higher in the communities served by Singleton (S). Gentamicin resistance alone was higher in communities served by, West Wales General (J), and Llandough (P). Hospital In-Patient and Out-Patient MRSA (n=890 in 2012) The trends in antimicrobial resistance for both hospital in-patient and out-patient MRSA are similar to those seen in the community, with no statistically significant changes in the resistance rates for any of the agents listed between 2011 and 2012, but increasing trend in resistance for fusidic acid, gentamicin, mupirocin and tetracycline. Some of the same local patterns of resistance seen in the community were also reflected in hospital patients from the same geographical area, with notably high fusidic acid and tetracycline rates in patients from Wrexham Maelor (H) and Ysbyty Glan Clwyd (L), and high gentamicin and mupirocin rates in patients from Morriston (E), and Singleton (S) hospitals: See Tables 25 and 26. 44

Section 4.4: Antimicrobial resistance rates for other pathogens. The data in this section of the report comprises other pathogens which may commonly cause important infections other than bacteraemia. The data is for all specimens from all locations (community, in-patient and out-patient). Haemophilus influenzae Streptococcus pneumoniae Streptococcus pyogenes Campylobacter species Neisseria gonorrhoeae 45

Table 27: Haemophilus influenzae - all specimens and all locations TABLE 27: Haemophilus influenzae, all specimens all locations Resistance rates including (95% Confidence Intervals) Duplicate Cut Off: 14 days in-patients and 91 days community and out-patients Time period: 1 January - 31 December 2012 Location Code AMO (95% CI) COA (95% CI) TET (95% CI) A (n=211) 27.0 (21.5, 33.4) 10.9 (7.4, 15.8) 0.9 (0.3, 3.4) B (n=180) 28.5 (22.4, 35.5) 11.7 (7.8, 17.3) 1.7 (0.6, 4.9) C (n=631) 24.2 (21.0, 27.7) 12.3 (10.0, 15.1) 0.8 (0.3, 1.9) D (n=1384) 20.5 (18.7, 22.5) 6.0 (5.0, 7.2) 1.0 (0.7, 1.6) E (n=81) 31.3 (22.2, 42.1) 15.8 (9.3, 25.6) 0.0 (0.0, 4.5) F (n=843) 20.0 (17.5, 22.9) 7.8 (6.2, 9.8) 1.1 (0.6, 2.0) G (n=110) 33.3 (24.5, 43.6) 4.5 (1.8, 11.0) 2.2 (0.6, 7.8) H (n=673) 25.3 (22.0, 28.9) 0.5 (0.2, 1.5) 1.4 (0.7, 2.6) J (n=529) 32.5 (28.7, 36.6) 16.1 (13.2, 19.5) 1.5 (0.8, 3.0) K (n=685) 22.9 (19.9, 26.2) 9.2 (7.3, 11.6) L (n=541) 40.5 (36.4, 44.7) 11.5 (9.0, 14.4) 0.4 (0.1, 1.5) M (n=207) 25.6 (20.1, 32.0) 7.7 (4.8, 12.2) 0.5 (0.1, 2.7) N (n=440) 15.3 (12.2, 18.9) 7.3 (5.2, 10.1) 1.1 (0.5, 2.6) P (n=197) 23.4 (18.0, 29.7) 9.7 (6.3, 14.6) 3.0 (1.4, 6.5) Q (n=21) 14.3 (5.0, 34.6) 0.0 (0.0, 15.5) 0.0 (0.0, 15.5) R (n=57) 33.3 (22.5, 46.3) 17.5 (9.8, 29.4) 0.0 (0.0, 6.3) S (n=750) 28.3 (25.2, 31.6) 13.5 (11.2, 16.1) 1.1 (0.6, 2.1) T (n=29) 24.1 (12.2, 42.1) 11.1 (3.9, 28.1) 0.0 (0.0, 11.7) All-Wales: Resistance rates 24.9 (23.9, 25.8) 9.0 (8.3, 9.6) 1.1 (0.9, 1.4) All-Wales: Number of isolates 7,835 7,703 7,094 Key: AMO = amoxicillin, COA = co-amoxiclav, TET = tetracycline Note: The range of resistance is outlined with boxes e.g. the range of resistance to amoxicillin was 14.3% - 40.5%; individual hospital rates statistically higher than the All-Wales rate are highlighted in colour. 46

2005 2012 Resistance (%) Haemophilus influenzae (n=7,934 in 2012) The All-Wales pattern of antimicrobial resistance for Haemophilus influenzae from all specimens/locations is shown in Figure 21 & Table 27; with an increase in the trend of resistance to co-amoxiclav. 28 26 24 22 20 18 16 14 12 10 8 6 4 2 0 AMO COA TET Figure 21: All-Wales antimicrobial resistance rates for H. influenzae; all specimens and all locations (2005 to 2012) Locally, there was variability in co-amoxiclav resistance rates within Wales with higher rates of resistance being seen in the hospitals and the communities served by laboratories at Glangwili (J), and Prince Philip (R). 47

Table 28: Streptococcus pneumoniae - all specimens and all locations TABLE 28: Streptococcus pneumoniae, all specimens all locations Resistance rates including (95% Confidence Intervals) Duplicate Cut Off: 14 days in-patients and 91 days community and out-patients Time period: 1 January - 31 December 2012 Location Code ERY (95% CI) PEN (95% CI) TET (95% CI) A (n=101) 2.0 (0.5, 6.9) 0.0 (0.0, 3.7) 2.0 (0.5, 6.9) B (n=68) 13.4 (7.2, 23.6) 0.0 (0.0, 5.3) 9.1 (4.2, 18.4) C (n=179) 33.3 (12.1, 64.6) 5.6 (3.1, 10.0) 13.2 (9.0, 19.1) D (n=528) 10.6 (8.2, 13.5) 3.4 (2.2, 5.3) 8.7 (6.6, 11.5) E (n=45) 11.6 (5.1, 24.5) 2.3 (0.4, 11.8) 5.7 (1.6, 18.6) F (n=329) 9.3 (6.6, 12.9) 5.2 (3.3, 8.2) 3.1 (1.7, 5.6) G (n=48) 7.7 (2.7, 20.3) 2.5 (0.4, 12.9) 0.0 (0.0, 9.0) H (n=306) 15.8 (11.8, 20.9) 7.4 (4.9, 11.0) 14.8 (10.7, 20.1) J (n=202) 8.4 (5.3, 13.1) 4.5 (2.4, 8.2) 4.0 (2.0, 7.6) K (n=270) 10.7 (7.6, 15.0) 3.7 (2.0, 6.7) 4.8 (2.8, 8.1) L (n=216) 9.3 (6.1, 14.0) 1.9 (0.7, 4.7) 4.2 (2.2, 7.7) M (n=90) 14.4 (8.6, 23.2) 5.6 (2.4, 12.4) 13.5 (7.9, 22.1) N (n=103) 18.8 (12.4, 27.5) 5.8 (2.7, 12.1) 15.5 (9.6, 24.0) P (n=45) 18.6 (9.7, 32.6) 2.2 (0.4, 11.6) 13.6 (6.4, 26.7) R (n=24) 37.5 (21.2, 57.3) 8.3 (2.3, 25.8) 16.7 (6.7, 35.9) S (n=340) 9.4 (6.7, 13.1) 5.0 (3.2, 7.9) 3.8 (2.0, 7.0) T (n=19) 15.8 (5.5, 37.6) 5.3 (0.9, 24.6) 12.5 (3.5, 36.0) All-Wales: Resistance rates 11.2 (10.0, 12.4) 4.3 (3.6, 5.1) 7.4 (6.5, 8.5) All-Wales: Number of isolates 2,638 2,895 2,680 Key: ERY = erythromycin, PEN = penicillin, TET = tetracycline 48

2005 2012 Resistance (%) Streptococcus pneumoniae (n=2,919 in 2012) The All-Wales pattern of antimicrobial resistance for Streptococcus pneumoniae from all specimens and all locations is shown in Figure 22 & Table 28; with a small but statistically significant increase in the resistance rates to all three agents between 2010 and 2012. 14 12 10 8 6 4 2 0 ERY PEN TET Figure 22: All-Wales antimicrobial resistance rates for S. pneumoniae; All specimens and all locations (2005 to 2012) The rates for all three agents are higher than the rates for S. pneumoniae isolates from blood culture: See Figure 14.There was some variation in the penicillin resistance across Wales with higher rates being seen across ABMU Health Board in 2011 (Hospitals E & T). Locally, there was variability in erythromycin and tetracycline resistance rates within Wales with higher rates of resistance seen in the hospital and the communities served by Wrexham Maelor (H) and Prince Philip (R). 49

2005 2012 Resistance (%) Streptococcus pyogenes (n=3,473 in 2012) The All-Wales pattern of antimicrobial resistance for Streptococcus pyogenes from all specimens/locations is shown in Figure 23; with a statistically significant increase in resistance to erythromycin and tetracycline between 2011 and 2012. 16 14 12 10 8 6 4 2 0 ERY PEN TET Figure 23: All-Wales antimicrobial resistance rates for S. pyogenes; all specimens and all locations (2005 to 2012) There were no validated cases of penicillin resistant S. pyogenes in Wales from 2005 to 2012. 50

2005 2012 Resistance (%) Campylobacter species (n=3,067 in 2012) The All-Wales pattern of antimicrobial resistance for Campylobacter spp. from all locations is shown in Figure 24; with a statistically significant change in the rate for ciprofloxacin between 2011 and 2012. 44 42 40 38 36 34 32 30 28 26 24 22 20 18 16 14 12 10 8 6 4 2 0 CIP ERY Figure 24: All-Wales antimicrobial resistance rates for Campylobacter spp.; all specimens and all locations (2005 to 2012) 51