European Antimicrobial Resistance Surveillance System (EARSS) in Scotland: 2004

European Antimicrobial Resistance Surveillance System (EARSS) in Scotland: 2004 SECOND ANNUAL REPORT MJ Coyne 1, SJ Dancer 1, G Edwards 2, 3, D Morrison 2. 1 Health Protection Scotland, 2 Scottish MRSA Reference Laboratory, 3 Scottish Meningococcus and Pneumococcus Reference Laboratory. SUMMARY This is the second annual report describing a national surveillance scheme for Scotland. This scheme collects data on invasive Staphylococcus aureus and Streptococcus pneumoniae from all NHS clinical microbiology laboratories. During 2004, 1691 S.aureus isolates were received. Six hundred and ninety (41%) of these were resistant to methicillin; 501 (73%) were of type EMRSA-15, 163 (24%) were EMRSA-16 and 26 (4%) were of other type. Five hundred and thirty eight S.pneumoniae isolates were received during 2004. Eighteen (3.4%) were non-susceptible to penicillin and 69 (13.0%) were non-susceptible to erythromycin. These data provide a baseline for surveillance and a means for the identification of significant trends for the future. INTRODUCTION The European Antimicrobial Resistance Surveillance System (EARSS) is an international network of national surveillance systems which was started in 1998 with funding from the European Commission. 1,2 The scheme aims to collect comparable and reliable antimicrobial resistance data on invasive isolates of Staphylococcus aureus (including methicillin-resistant Staphylococcus aureus (MRSA)), Streptococcus pneumoniae, Escherichia coli and Enterococcus faecium/faecalis. At present, information is routinely collected from more than 750 microbiology laboratories in 28 countries. The programme provides an opportunity for anonymised patient specific data on bacteraemias to become available from all NHS hospitals in Scotland. EARSS has been in operation in Scotland since January 2002 for S.pneumoniae and July 2002 for S.aureus. At present, no data is collected for E.coli and E.faecium/faecalis. METHODS Every diagnostic microbiology laboratory in Scotland sends all first blood or cerebrospinal fluid (CSF) isolates of S.aureus and S.pneumoniae from every patient to the Scottish MRSA and Scottish Meningococcus and Pneumococcus Reference Laboratories respectively. These laboratories confirm the identification and determine a range of antimicrobial susceptibilities for each isolate. The Reference Laboratories forward these data to HPS, who then send them to the UK coordinating centre at HPA Colindale, who forward it, along with data from England, Wales and 1

Northern Ireland, to the European base at the National Institute of Public Health and the Environment (RIVM), in Bilthoven, Holland. Investigations for S.aureus All isolates were tested for the meca gene by Polymerase Chain Reaction (PCR), and for susceptibility to eighteen (MRSA) or six (MSSA) antibiotics including methicillin by Stokes disc diffusion method, or from April 2004, by an automated method. BHI agar containing 5 mg/l of vancomycin was used to screen for reduced susceptibility to glycopeptides. Where meca PCR was inconsistent with methicillin susceptibility by Stokes or automated method, isolates were further tested by determining oxacillin and cefoxitin MIC s (E-test method, Bio-Stat, Manchester, UK) as follows: suspensions of test organism were prepared to 0.5 McFarland standard and used to inoculate Mueller Hinton agar (Oxoid) containing 2% sodium chloride. E-test strips were applied to the agar and plates were incubated at 35 C for 24 hours. Mupirocin high-level resistance was confirmed by PCR amplification of mupa gene. The hospital department from which the specimen originated was recorded, as well as possible association with an intravascular device. Investigations for Streptococcus pneumoniae Isolate identities were confirmed as pneumococci by antigen testing. Co-agglutination testing was used for serogrouping/typing. The E-test method (Bio-Stat, Manchester, UK) was used for antimicrobial susceptibility measurement 3 : suspensions of test organism were prepared to 0.5 McFarland standard and used to inoculate Mueller Hinton agar plates containing 5% lysed horse blood (Oxoid). E-test strips were applied to the agar and plates were incubated at 37 C overnight in a 5% carbon dioxide atmosphere. Susceptibilities to penicillin, erythromycin and ciprofloxacin were determined for each isolate. RESULTS S.aureus Table 1 shows the number of invasive staphylococcal isolates received at the Scottish MRSA Reference Laboratory during the inclusive period January to December 2004. MRSA makes up 41% of all S.aureus bacteraemias. MRSA molecular typing The results from MRSA molecular typing are shown in Figure 1 and Table 2. EMRSA-15 is the predominant type in Scotland, accounting for 72.6% of all isolates reported. The percentage of EMRSA-16 is 23.6%. The other group accounts for 3.8% of all isolates and is composed of nine different types. Antimicrobial susceptibilities for S.aureus Figure 2 and Table 3 detail a selection of MRSA antimicrobial susceptibilities. Six point five percent of Scottish blood isolates were resistant to fucidin, 11.1% to gentamicin, 4.3% to mupirocin, 3.2% to rifampicin, 4.6% to tetracycline and 16.2% to 2

trimethoprim. Most isolates (78.4%) were resistant to erythromycin, and 20% of the remaining 22% susceptible to erythromycin were of type EMRSA-15. MSSA susceptibilities to erythromycin and fucidin are listed in Table 4. The fucidin resistance rate among MSSA is comparable to the MRSA rate: 8.8% MSSA nonsusceptible, compared with 6.4% for MRSA. However, there are significant differences between the erythromycin rates: 7.6% MSSA were resistant to erythromycin, compared with 78.4% for MRSA. Figure 3 and Table 5 detail the proportion of S.aureus / MRSA bacteraemias by hospital speciality. The highest MRSA rates were found in the following departments: HDU/ICU (51.6%), paediatric ICU (50.0%) and Care of the Elderly (49.4%). The lowest MRSA rates (and total S.aureus bacteraemias) were found in paediatrics and obstetrics/gynaecology with rates at 0 and 11.1% respectively. Figure 4 and Table 6 detail the MRSA type by hospital speciality. Table 7 details the association between intravascular device and infection by Division. Definitive details on intravascular device association were provided for 379 isolates. Two hundred and thirty-six (67%) of these were not associated with intravascular device and 143 (38%) were associated with intravascular device. S.pneumoniae Figure 5 and Table 8 show the number of invasive isolates received at the Scottish Pneumococcal and Meningococcal Reference Laboratory during 2004. The majority of specimens (97%) come from blood, though this may not truly reflect the proportion since some patients may have an isolate from both blood and cerebrospinal fluid but first isolates only are reported. Susceptibilities to penicillin, erythromycin and ciprofloxacin from all laboratories are shown in Figure 6 and Table 9. Table 10 shows susceptibility data by Division. Overall the rate for penicillin non-susceptible S.pneumoniae was 3.4%, erythromycin non-susceptible S.pneumoniae 12.3% and ciprofloxacin non-susceptible S.pneumoniae 23.7%. Figure 7 and Table 11 show the serotype distribution for all isolates. DISCUSSION The proportion of methicillin-resistant staphylococci in total numbers of staphylococci from blood has remained consistent between 2003 and 2004: 41% for both years. Scotland s rate is not significantly different to that of the rest of the UK, but still remains amongst the highest in Europe. 2 There may be an association between S.aureus bacteraemia and the presence of an intravascular device and it is important to improve the quality of reporting for this field. The rate of penicillin and erythromycin resistance in invasive pneumococci is relatively low in Scotland, at 3.4% and 13.0% respectively. There has been a small increase since 2003 (from 3.1% 3

penicillin non-susceptible and 12.3 erythromycin non-susceptible) however only time will determine if this remains to be the case. ACKNOWLEDGEMENTS We would like to acknowledge all clinical and scientific microbiologists who have collaborated in this programme and all staff at the Scottish MRSA and Scottish Meningococcus and Pneumococcus Reference Laboratories. Without their help, we could not have introduced this surveillance scheme, nor obtained this data. REFERENCES 1. Bronzwaer SL, Goettsch W, Olsson-Liljequist B, Wale MC, Vatopou AC, Sprenger MJ. European Antimicrobial Resistance Surveillance System (EARSS): objectives and organisation. Euro Surveill 1999; 4: 41-44. 2. www.earss.rivm.nl 3. Kyaw MH, Christie P, Clarke SC, Jones IG, Campbell H. Invasive pneumococcal disease in Scotland 1999-2001: use of record linkage to explore associations between patients and disease in relation to future vaccination policy. Clin Infect Dis 2003; 37: 1283-1291. 4

Table 1. Episodes of S.aureus bacteraemia in Scotland reported through EARSS 2004. Period No. S.aureus No. MSSA No. MRSA %MRSA Jan-Mar 436 248 188 43.1 Apr-Jun 417 260 157 37.6 Jul-Sep 378 212 166 43.9 Oct-Dec 460 281 179 39.0 Total 1691 1001 690 40.8 MSSA: methicillin-susceptible S.aureus; MRSA: methicillin-resistant S.aureus 5

Fife North Glasgow Lanarkshire Tayside Lothian Universities Grampian Argyll & Clyde South Glasgow West Lothian Highland Dumfries & Galloway Figure 1. MRSA isolates by Division, 2004. 180 160 140 120 100 80 60 40 20 0 6 Other E16 E15 No. isolates Orkney Shetlend Western Isles Yorkhill Golden Jubilee Forth Valley Ayrshire & Arran Borders

Table 2. MRSA isolates by Division, 2004. Division Name No. MRSA E15 E16 Other Argyll & Clyde 35 25 10 0 Ayrshire & Arran 6 3 1 2 Borders 6 5 1 0 Dumfries & Galloway 19 16 3 0 Fife 41 34 6 1 Forth Valley 5 4 1 0 Golden Jubilee 3 2 1 0 Grampian 50 23 20 7 Highland 11 9 2 0 Lanarkshire 57 34 22 1 Lothian Universities 141 105 36 0 North Glasgow 158 116 38 4 Orkney 0 0 0 0 Shetland 0 0 0 0 South Glasgow 42 34 8 0 Tayside 95 78 9 8 West Lothian 21 13 5 3 Western Isles 0 0 0 0 Yorkhill 0 0 0 0 Total 690 501 163 26 Percentage - 72.6 23.6 3.8 7

Rifampicin Mupirocin Tetracycline Figure 2. EARSS MRSA susceptibility data, 2004. 800 700 600 500 400 300 200 100 0 8 Non susceptible Susceptible No. isolates Erythromycin Trimethoprim Gentamicin Fucidin

Table 3. EARSS MRSA susceptibility data (690 isolates tested), January- December 2004. Antimicrobial No. Resistant No. Intermediate No. Sensitive % Non susceptible Erythromycin 536 5 149 78.4 Fucidin 12 33 646 6.5 Gentamicin 58 19 614 11.1 Mupirocin 30* - 661 4.3 Rifampicin 21 1 669 3.2 Tetracycline 31 1 659 4.6 Trimethoprim 107 1 583 16.2 *Mupirocin resistant isolates: 9 low level, 21 high level. Table 4. EARSS MSSA susceptibility data (1000 isolates tested), 2004. Antimicrobial No. Resistant No. Intermediate No. Sensitive % Non susceptible Erythromycin 61 15 924 7.6 Fucidin 57 31 912 8.8 MIC breakpoints (mg/l): erythromycin intermediate >0.25<1, erythromycin resistant 1; fucidin intermediate 1-2, fucidin resistant 2; gentamicin intermediate >1 and <2, gentamicin resistant 2; mupirocin low level 8 and 256, mupirocin high level 512; rifampicin intermediate >0.06<0.12, rifampicin resistant 0.1; tetracycline intermediate >1<2, tetracycline resistant 2; trimethoprim intermediate >0.5<1, trimethoprim resistant 1. 9

Figure 3. Episodes of S.aureus bacteraemia in Scotland reported through EARSS 2004, by speciality. 400 350 300 250 200 150 100 50 0 MRSA MSSA No. isolates Obs/Gyn Paediatric ICU ID Paediatrics Oncology Orthopaedic Care of Elderly Other Unknown A&E HDU/ICU Surgery Renal Not stated Medicine 10

Table 5. Episodes of S.aureus bacteraemia in Scotland reported through EARSS 2004, by speciality. Department S.aureus MRSA % MRSA A&E 95 26 27.4 Care of Elderly 79 39 49.4 HDU/ICU 126 65 51.6 ID 33 9 27.3 Medicine 369 141 38.2 Obs/Gynae 9 1 11.1 Oncology 52 24 46.2 Orthopaedic 52 21 40.4 Other 82 38 46.3 Paediatric ICU 14 7 50.0 Paediatrics 34 0 0.0 Renal 235 94 40.0 Surgery 169 81 47.9 Unknown 93 37 39.8 Not stated 249 107 43.0 Total 1691 690 40.8 11

Medicine Not stated Renal Surgery HDU/ICU Unknown Care of Elderly Other A&E Oncology Figure 4. MRSA type by speciality. 160 140 120 100 80 60 40 20 0 12 Other E16 E15 No. isolates Paediatrics Obs/Gynae Paediatric ICU Infectious diseases Orthopaedic

Table 6. MRSA type by speciality. HOSPITAL DEPARTMENT E15 E16 Other Paediatrics 0 0 0 Obs/Gynae 1 0 0 Paediatric ICU 6 1 0 Infectious diseases 7 2 0 Orthopaedic 13 8 0 Oncology 18 6 0 A&E 21 4 1 Other 27 6 5 Unknown 30 6 1 Care of Elderly 37 2 0 HDU/ICU 31 32 2 Surgery 55 22 4 Renal 72 20 2 Not stated 80 23 4 Medicine 103 31 7 13

Table 7. Intravascular device association by Division. Division No Yes Unknown Not stated Total Argyll & Clyde 11 7 45 25 88 Ayrshire & Arran 1 0 1 10 12 Borders 5 1 12 5 23 Dumfries & Galloway 1 4 35 14 54 Fife 6 6 39 34 85 Forth Valley 4 1 12 15 32 Golden Jubilee 0 0 5 1 6 Grampian 51 9 61 55 176 Highland 5 4 20 16 45 Lanarkshire 6 4 34 72 116 Lothian Universities 5 17 117 180 319 North Glasgow 9 5 221 130 365 South Glasgow 63 6 10 30 109 Tayside 59 72 18 37 186 West Lothian 3 5 5 41 54 Yorkhill 7 2 3 9 21 Total 236 143 638 674 1691 14

Figure 5. Invasive EARSS S.pneumoniae isolates, 2004. No. isolates 200 180 160 140 120 100 80 60 40 20 0 Jan-Mar Apr-Jun Jul-Sep Oct-Dec CSF Blood Culture CSF = cerebrospinal fluid Table 8. Invasive EARSS S.pneumoniae isolates, 2004. Period No. S.pneumoniae No. Blood Culture No. CSF Jan-Mar 189 184 5 Apr-Jun 145 141 4 Jul-Sep 91 90 1 Oct-Dec 113 109 4 Total 538 524 14 15

Figure 6. EARSS susceptibility data S.pneumoniae, January to December 2004. 600 500 No. isolates 400 300 200 Non susceptible Susceptible 100 0 Penicllin Erythromycin Ciprofloxacin Table 9. EARSS susceptibility data S.pneumoniae (532 isolates tested)*, January to December 2004. Antimicrobial No. In Group % Resistance Penicillin low level 18 3.4 Penicillin high level 0 0 Erythromycin intermediate 1 0.2 Erythromycin resistant 68 12.8 Ciprofloxacin intermediate 132 23.3 Ciprofloxacin resistant 2 0.4 * not all isolates were tested against all antibiotics MIC breakpoints (mg/l): ciprofloxacin intermediate >1 and <4; ciprofloxacin resistant 4; erythromycin intermediate >0.25 and <1; erythromycin resistant 1; penicillin low level >0.064 and <2; penicillin high level 2. 16

Table 10. Invasive S.pneumoniae isolates received through EARSS programme, January-December 20043, by trust (532 isolates tested)*. Division Name No tested PNSP ENSP Western Isles 2 0 (0.0%) 0 (0.0%) Dumfries & Galloway 13 1 (7.7%) 2 (15.4%) Highland 16 0 (0.0%) 3 (18.8%) Borders 18 1 (5.6%) 2 (11.1%) West Lothian 19 0 (0.0%) 1 (5.3%) Forth Valley 26 2 (7.7%) 5 (19.2%) Ayrshire & Arran 27 0 (0.0%) 2 (7.4%) Yorkhill 27 2 (7.4%) 7 (25.9%) Fife 29 0 (0.0%) 6 (20.7%) Argyll & Clyde 34 1 (2.9%) 6 (17.6%) Grampian 46 0 (0.0%) 4 (8.7%) South Glasgow 47 3 (6.4%) 2 (4.3%) Tayside 48 1 (2.1%) 8 (16.7%) North Glasgow 56 1 (1.8%) 1 (1.8%) Lanarkshire 57 2 (3.5%) 11 (19.3%) Lothian Universities 67 4 (6.0%) 9 (13.4%) Total 532 18 (3.4%) 69 (13.0%) * not all isolates were tested against all antibiotics PNSP = penicillin non-susceptible S.pneumoniae; ENSP = erythromycin nonsusceptible S.pneumoniae; MIC breakpoints (mg/l): PNSP >0.064; ENSP >0.25. 17

PNE035 Other PNE023 PNE033 PNE022 PNE020 PNE019 PNE018 PNE017 PNE016 PNE013 PNE014 PNE015 PNE012 PNE011 Figure 7. S.pneumoniae serotype distribution 100 90 80 70 60 50 40 30 20 10 0 Serotype 18 No. isolates PNE001 PNE003 PNE004 PNE005 PNE006 PNE007 PNE008 PNE009 PNE010

Table 11. S.pneumoniae serotype distribution. Serotype No. isolates PNE001 58 PNE003 31 PNE004 37 PNE005 1 PNE006 36 PNE007 18 PNE008 30 PNE009 44 PNE010 5 PNE011 8 PNE012 19 PNE013 2 PNE014 95 PNE015 7 PNE016 2 PNE017 1 PNE018 27 PNE019 36 PNE020 12 PNE022 18 PNE023 33 PNE033 3 PNE035 4 Other 11 19