Introduction. Journal of Antimicrobial Chemotherapy (2008) 62, Suppl. 2, ii87 ii95 doi: /jac/dkn355

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1 Journal of Antimicrobial Chemotherapy (2008) 62, Suppl. 2, ii87 ii95 doi: /jac/dkn355 Non-susceptibility trends and serotype distributions among Streptococcus pneumoniae from community-acquired respiratory tract infections and from bacteraemias in the UK and Ireland, 1999 to 2007 David J. Farrell 1 *, David Felmingham 1, Jemma Shackcloth 1, Laura Williams 1, Kirsty Maher 1, Russell Hope 2, David M. Livermore 2, Robert C. George 2, Geraldine Brick 2, Siobhan Martin 2 and Rosy Reynolds 3 on behalf of the BSAC Working Parties on Resistance Surveillance 1 Quotient Bioresearch, Microbiology, 7-9 William Road, London NW1 3ER, UK; 2 Health Protection Agency Centre for Infections, 61 Colindale Avenue, London NW9 5EQ, UK; 3 Department of Medical Microbiology, Southmead Hospital, Southmead Road, Bristol BS10 5NB, UK Objectives: Pneumococcal disease is prevalent and is a cause of significant morbidity and mortality in the UK and Ireland. We describe the antimicrobial susceptibility and serotype distributions of Streptococcus pneumoniae causing bacteraemia and community-acquired pneumonia in these countries from 1999/2000 to 2006/7, predominantly prior to the introduction of the heptavalent pneumococcal conjugate vaccine (PCV7) into the standard vaccination schedule in September Methods: The BSAC Respiratory and Bacteraemia Resistance Surveillance Programmes collected S. pneumoniae from sentinel laboratories distributed across the UK and Ireland. A central laboratory for each programme re-identified the isolates, determined their serotypes and measured MICs by the BSAC agar dilution method. Results: The prevalence of antimicrobial non-susceptibility, although significant, was generally below the global average. There was no convincing evidence of increasing non-susceptibility over time in either study. The results showed clear differences in the serotype distribution between respiratory and blood isolates, but suggested that PCV7 would provide adequate coverage of invasive isolates in the UK and Ireland. A significant and rapid increase of the non-vaccine serotype 1 among blood isolates from 2001 to 2006 was worrying, given the spread of hypervirulent serotype 1 clones elsewhere in the world. Conclusions: Continued surveillance of both antimicrobial non-susceptibility and serotype distribution changes following the introduction of PCV7 into the routine immunization schedule in the UK and Ireland is imperative. The data presented here, largely obtained prior to the introduction of PCV7 in the UK, provide a valuable baseline against which to monitor changes in antimicrobial non-susceptibility and serotype distribution and hence to identify the expansion of any significant clones. Keywords: surveillance, susceptibility tests, respiratory Introduction Based on various national data sources and GP sentinel surveillance systems, it was recently estimated that, in England and Wales, there are around 5800 hospitalizations for invasive pneumococcal disease, approximately for lobar pneumonia and greater than for otitis media anually. 1 In addition, it was estimated that there were possibly GP consultations for pneumococcal community-acquired pneumonia and for otitis media. 1 Data available from the Health Protection Agency (HPA) web site show that a total of cases of invasive pneumococcal disease were recorded in England and Wales from 2000 to These data almost certainly underestimate the true burden of disease, and hence pneumococcal infections cause a considerable degree of morbidity in England and Wales.... *Corresponding author. Present address: Ontario Public Health Laboratories, Ministry of Health and Long-Term Care, 81 Resources Road, Toronto, Ontario, Canada M9P 3T1. Tel: þ ; Fax: þ ; david.farrell@oahpp.ca... ii87 # The Author Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please journals.permissions@oxfordjournals.org

2 Farrell et al. A number of international and national surveillance studies have documented high levels of antibacterial resistance in Streptococcus pneumoniae, 3 5 leading to concerns over the continued clinical utility of agents such as the b-lactams and macrolides for the empirical treatment of community-acquired respiratory tract infections. 6 However, non-susceptibility rates for penicillin and macrolides have been reported to be lower in the UK compared with global data. 7,8 The heptavalent pneumococcal conjugate vaccine (PCV7; Prevenar w ; Wyeth Lederle Vaccines, Pearl River, New York, NY, USA) was introduced in the USA in February The vaccine is licensed for children 5 years, and there is a general recommendation for its use in all children,2 years. PCV7 provides coverage against S. pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F and 23F. The vaccine was licensed in Europe in 2001 and introduced into the paediatric immunization schedules in the UK from 4 September ,10 Antimicrobial resistance in S. pneumoniae is closely associated with particular serotypes, including those represented in the PCV7 vaccine. 11 In the USA, introduction of PCV7 has been accompanied by reductions in both the incidence of invasive pneumococcal disease and penicillin and macrolide non-susceptibility among invasive pneumococcal disease isolates However, resistance in non-vaccine strains has increased. 15 There is evidence that the prevalence of invasive pneumococcal disease is now increasing in serotypes not covered by PCV7 especially multidrug-resistant serotype 19A. 16 In Spain, recent data have shown an increase in invasive pneumococcal disease with virulent clones of non-vaccine strains following the introduction of the vaccine though accompanied here by a decrease in antibiotic resistance. 17 Thus, the impact of vaccine on invasive pneumococcal disease and antimicrobial prevalence differs among countries. It may be that the impact of PCV7 introduction will vary by country, according to the serotypes and antibiotic resistance types that are already present. The aim of this study was to analyse the data from the BSAC Bacteraemia and Respiratory studies to observe changes in antimicrobial non-susceptibility and serotype distribution over the study periods. It is hoped that this analysis will be useful to monitor future changes to help understand the impact of policy and practice changes in the UK and Ireland such as the widescale introduction of PCV7 or the introduction of new antibiotics or antibiotic therapy recommendations. Materials and methods The collection strategy, identification methods, MIC determination, serotyping and statistical analysis methods for the BSAC bacteraemia and respiratory resistance surveillance studies are described elsewhere in this supplement. 18,19 Results Isolates and patient characteristics In its 6 years of operation to date ( ), the BSAC Bacteraemia Surveillance collected 1388 S. pneumoniae isolates. In its 8 years of operation to date ( ), the BSAC Respiratory Surveillance collected 5810 S. pneumoniae isolates, with the great majority (90.6%) collected from sputum specimens. Distribution by country, care setting, medical specialty and age for both studies is shown in Tables 1 and 2. In the bacteraemia study, for 66.0% of the isolates, the presumed focus of infection was the respiratory tract, whereas CSF was given as a presumed focus of infection in only 48 isolates (3.5%). Although all age groups were well represented, over half of the isolates in both studies were obtained from patients aged 60 years or older (Table 2). Non-susceptibility rates and trends The proportions of isolates susceptible or resistant to a range of antibiotics, along with summary MIC data for both studies, are presented in Tables 3 5. For antibacterials common to both studies, results are similar, except that MICs of ciprofloxacin are typically half a doubling dilution (1.4-fold) higher in isolates from the bacteraemia study compared with the respiratory study. For both studies, penicillin, ertapenem and tetracycline susceptibilities were.90%; cefotaxime susceptibility was 98.5% and erythromycin susceptibility was.85%. Random effects logistic regression demonstrated no convincing evidence of a trend in non-susceptibility over time in either study, although there was clear evidence of intercentre variation in the respiratory study (P, for most antimicrobials). Penicillin non-susceptibility was significantly more prevalent in hospital-acquired bacteraemias than other bacteraemias (10.5% versus 4.5%, P ¼ ). This was not the case for erythromycin non-susceptibility (13.9% versus 15.0%, P ¼ 0.73), tetracycline non-susceptibility (4.9% versus 3.6%, P ¼ 0.27), ciprofloxacin resistance (13.3% versus 14.2%, P ¼ 0.86) or cefotaxime non-susceptibility (2.5% versus 1.2%, P ¼ 0.06). This difference was not due to resistant hospital serotypes, as it remained significant after accounting for the top six serotypes in the analysis and could be seen within individual serotypes, e.g. 14 (16% versus 3%) and 23F (14% versus 3%). In the bacteraemia study, there was no evidence of significant differences in non-susceptibility between age groups or sex, nor a smooth trend in non-susceptibility with increasing age. In the respiratory study, although there was no evidence of significant differences in non-susceptibility by sex, there was evidence of significant differences in non-susceptibility between age groups for cefuroxime (P ¼ ) and penicillin (P ¼ ). The pattern for the b-lactams was for least non-susceptibility in the middle age group (20 59 years) and increasing non-susceptibility in the younger and older age groups (Table 6). The pattern for the fluoroquinolones was different there was a clearly significant rising trend in ciprofloxacin resistance (P ¼ ) and moxifloxacin non-susceptibility (P ¼ ) with increasing age (Table 6). The in vitro activities of the newer antibacterials (ceftobiprole, doripenem, ertapenem, faropenem, gemifloxacin, linezolid, meropenem and telavancin) were very high against S. pneumoniae isolated from both studies (Table 3). Serotypes In the bacteraemia study, there was a significant change in the serotype distribution by year of study (Figure 1, P ¼ ). The major change was a steady increase in the proportion of serotype 1 isolates by year from 4.0% in 2001 to 15.6% in 2006 (P, ). ii88

3 Table 1. Isolate and patient characteristics Non-susceptibility and serotypes in S. pneumoniae Bacteraemia study ( ) Respiratory study ( ) N Distribution by: country England 67.2%, Wales 8.1%, Scotland 8.2%, Northern Ireland 8.2%, Ireland 8.2% Table 2. Age distribution of patients Bacteraemia programme Respiratory programme Age band (years) frequency percentage cumulative frequency percentage cumulative Unknown Table 3. Activity of antibiotics tested in both studies against S. pneumoniae isolated in the BSAC bacteraemia and respiratory surveillance studies Bacteraemia study England 61.7%, Wales 11.2%, Scotland 13.2%, Northern Ireland 3.7%, Ireland 10.2% sex female 46.1%, male 53.6%, unknown 0.3% female 42.2%, male 57.8%, unknown 0.3% care setting hospital,48 h 60.1% hospital,48 h 58.0% community and outpatients 14.5% general practitioner 40.3% hospital.48 h 23.3% nursing homes 1.3% unknown 2.1% unknown (but community-acquired ) 0.3% medical specialty general medicine 32.0%, accident and emergency 27.0%, paediatrics 9.2%, care of the elderly 6.5%, others (,5% each) 18.5%, unknown 6.8% data not collected Respiratory study N S% I% R% Min MIC 50 MIC 90 Max N S% I% R% Min MIC 50 MIC 90 Max Amoxicillin Ciprofloxacin Clindamycin Cefotaxime Erythromycin Ertapenem Minocycline Penicillin Tetracycline Tigecycline Min, MIC 50, MIC 90 and Max are given in mg/l. In the respiratory study, isolates collected from patients in hospital for 48 h were excluded, and serotype information was available only for the 749 isolates collected in the 2005/06 season. As the distribution of serotypes in the bacteraemia study changed significantly over time, we compared these respiratory isolates with the 354 blood isolates collected in 2005 and 2006 ii89

4 Farrell et al. Table 4. Activity of antibiotics tested exclusively in the BSAC respiratory surveillance study Antibiotic N S% I% R% Min MIC 50 MIC 90 Max Telavancin Piperacillin/tazobactam Vancomycin Ceftobiprole Daptomycin a Doripenem Gentamicin Imipenem Linezolid Meropenem Oxacillin Teicoplanin a Despite good in vitro activity, it has been demonstrated in clinical studies that daptomycin is not effective in the treatment of pneumonia. Table 5. Activity of antibiotics tested exclusively in the BSAC bacteraemia surveillance study Antibiotic N S% I% R% Min MIC 50 MIC 90 Max Cefaclor Clarithromycin Cefuroxime Faropenem Gemifloxacin Levofloxacin Moxifloxacin Trimethoprim Table 6. The BSAC respiratory surveillance study: percentage non-susceptible by age Age group (years) Cefaclor Cefotaxime Cefuroxime Ciprofloxacin a Clarithromycin Ertapenem Erythromycin Gemifloxacin Levofloxacin Moxifloxacin Penicillin Tetracycline a For ciprofloxacin, percentage resistant is given (not percentage non-susceptible). from community-acquired infections, i.e. again excluding those collected after more than 48 h in hospital. The results of this comparison are provided in Table 7. The serotype distribution differed markedly between S. pneumoniae from blood (Figure 2a) and lower respiratory (Figure 2b) sources (P, ). The top five respiratory serotypes, accounting for 41% of the total, were 19F, 23F, 6B, 3 and 6A; the top five bacteraemia isolates, totalling 54%, were 1, 14, 9V, 23F and 4. The most striking difference was the much higher proportion of the virulent serotype 1 isolates found in blood (17.2%), compared with lower respiratory infections (1.7%); in addition, 15.3% of blood versus 5.1% of respiratory isolates were serotype 14, and 2.8% versus 11.1% were serotype 19F. Nevertheless, PCV7 coverage was similar for community-acquired isolates from blood (46%) and respiratory sources (42%), but coverage by the 23-valent pneumococcal polysaccharide vaccine differed very significantly, being 73% in respiratory and 93% in bacteraemia isolates. As respiratory and bacteraemia isolates were tested in different central laboratories, the possibility of experimental bias was considered. The serotypes of 50 isolates, 25 from each programme, were therefore re-identified in both laboratories. There was agreement between the laboratories for 47 (94%) and disagreement for 3 (6%, 95% confidence interval: ). We compared the serotype distributions seen in the two programmes, matched them as closely as possible and noted the percentage that remained unmatched. In this way, we calculated that an identification disagreement rate of at least 23% would be required to generate the differences in serotype distribution actually seen between the ii90

5 Non-susceptibility and serotypes in S. pneumoniae % 15.0 programmes, and therefore, methodological differences were not responsible for this observation. We also considered whether the difference might be the result of different centres contributing to the two programmes, but the same patterns were seen when the analysis was restricted to the 438 isolates from the 10 centres contributing to both studies in this period. Considering all the isolates, from all available seasons and care settings, PCV7 coverage of S. pneumoniae from blood (but not respiratory sources) was significantly higher in children aged,5 years (P, ) at 77.0% versus,50% for all other age groups apart from those aged 80 years (54.3%). This pattern remained clear in community-acquired blood isolates, but was not significant for those obtained.48 h after hospital admission. Overall, 48.8% of the blood isolates and 41.7% of the respiratory isolates were of serotypes included in PCV7. In both studies, there was a significantly higher prevalence of erythromycin and penicillin non-susceptibility, and in the respiratory study only, cefuroxime and tetracycline non-susceptibility, in PCV7 serotypes compared with non-pcv7 serotypes (Table 8). Considering all bacteraemia isolates, differences in the serotype distribution between isolates obtained.48 h after hospital admission and others were significant (P ¼ ), although serotype 1 appeared to be less common in hospital-acquired infections (after 48 h, 5.3%) than others (10.5%). Discussion Year 2001 Year 2002 Year 2003 Year 2004 Year 2005 Year V 23F F 6B 7F Other Figure 1. Serotype distribution by study year for the bacteraemia study. The change in the serotype distribution was significant (P ¼ ) as a trend by multinomial logit. The data presented in these studies show that, against S. pneumoniae, the overall non-susceptibility prevalence for major use and newer antibacterials has not increased significantly during the first 6 years of this decade in the UK and Ireland. The rates of penicillin resistance (0.3% in both studies) and erythromycin non-susceptibility (14.6% and 12.0% in bacteraemia and respiratory study, respectively) were comparable with the rates of 3.1% and 18.0%, respectively, for the UK found in a large global surveillance study (PROTEKT) performed between 2001 and The penicillin and erythromycin nonsusceptibility rates found in these studies were below average compared with the 41 countries participating in the PROTEKT study, in which erythromycin resistance ranged by country from 0.0% to 93.5% (average 35.5%) and penicillin resistance from 0.0% to 66.0% (average 22.4%). Hence, although significant (especially for erythromycin), antimicrobial non-susceptibility in the UK and Ireland is below the global average. According to voluntary bacteraemia reports to the HPA s LabBase system, for England, Wales and Northern Ireland combined, the rate of penicillin resistance in pneumococci from bacteraemias and CSF peaked at 6.7% in 2000 and has been declining since that time to 2.5% in 2006, although the rates for Wales and Northern Ireland were higher (at 5% and 10%, respectively) than for England (ranging from 0.9% in the Southwest to 3.7% in London). 20 In contrast, the rates for erythromycin resistance have remained fairly constant at 9.3% to 14.3% with some regional variation, between 1993 and 2006 in England, Wales and Northern Ireland. 20 Livermore et al. 21 found that decreasing penicillin resistance in pneumococci in the UK followed reduced sales of oral b-lactams to UK pharmacies, and hence this may be a possible explanation for decreased penicillin resistance. However, the explanation is most likely more complex than this, as the same study observed that the same decrease in macrolide sales did not result in a concurrent decrease in macrolide resistance, and, conversely, in Ireland penicillin resistance decreased whereas b-lactam sales increased. In the bacteraemia study, the increased prevalence of penicillin (and possibly cefotaxime) non-susceptibility in hospital-acquired ii91

6 Farrell et al. (a) 250 PCV7 200 Number of isolates Number of isolates (b) B 9V 14 18C 19F 23F PCV7 4 6B 9V 14 18C 19F 23F 1 infection (infection presenting after the patient had been in hospital for.48 h) versus patients presenting with infection before or within 48 h of hospitalization is especially interesting. It is important to understand that acquiring such an infection after 48 h of hospitalization does not equate to transmission of the infectious agent while in hospital, although this is of course a possibility. Infection with S. pneumoniae usually begins by colonization of the upper and then lower respiratory tract, and hence it is most likely that these patients became ill in hospital with previously acquired strains. The most likely, but not definitive, mechanisms for this would be reduced immune status after prolonged hospitalization and selection of non-susceptible strains during 8 3 7F 22F 6A 19A 12F 9N 20 11A 33F 23A 16F Untyped 10A 15B 17F 31 15C 38 15A B 35F 10F 12B 18F 24F 37 7C 11H 16A 19C 3 6A Non-typeable 19A 23A 31 9N F 1 Serotype Serotype F 7FABC 9L 35F 35B 21 23B 37 17F 28A 10A 33A 34 10F 27 33B 22A 33F 36 9A NVFT 12F 13 18B 22A 24A 25F 29 3B 2 24F 28F 29 Figure 2. Distribution of serotypes by surveillance study. (a) Bacteraemia study and (b) respiratory study. NVFT, not viable for further testing. antimicrobial therapy. Treatment failure and increased morbidity and mortality have been associated with macrolide resistance in community-acquired pneumonia, 22 but the available data for penicillins suggest no such correlation in patients with or without bacteraemia, although there is a correlation with meningitis. 23 However, it is very difficult to define treatment failure in community-acquired pneumonia, and there are limited data to support this hypothesis. For instance, it could be that penicillin non-susceptibility results in increasing morbidity (and hence longer hospital stay) in the subgroup of patients acquiring infection while already in hospital. As with community-acquired bacteraemia, this study highlights that further research is required to 5 35A 38 ii92

7 Non-susceptibility and serotypes in S. pneumoniae Table 7. Serotypes in comparable blood and respiratory isolates collected during the season Serotype Number of isolates Percentage Cumulative percentage Bacteraemia V F B A A F C F N F F other serotypes a total Respiratory 19F F B A V non-typeable A A N C F F L F B other serotypes b total a Other serotypes n ¼ 14, all with,1% prevalence. b Other serotypes n ¼ 25, all with,1% prevalence. Serotypes included in PCV7 are shown in bold. determine the role of S. pneumoniae in hospital-acquired bacteraemia (and pneumonia) and the impact of antibiotic resistance on outcome. In a meta-analysis of.70 study reports on serogroup distributions among invasive blood isolates from Europe, PCV7 coverage of 78.6% and 48.2% for young children or older children and adults, respectively, has been reported. 24 The levels of PCV7 coverage found here in both the bacteraemia and respiratory studies are similar to these. However, the previously reported data gave information about serogroup rather than serotype coverage, as it was hoped that cross-coverage between serotypes in the same serogroup would occur, but in reality this is only partly true. Studies have demonstrated that significant cross-reactivity occurs between serotypes 6B (in PCV7 formulation) and 6A (not in PCV7) and between serotypes 19F (in PCV7) and 19A (not in PCV7) However, the carriage of serotype 6A was found to be higher than expected after vaccination in one study. 28 Also, there is now strong evidence that since the introduction of PCV7 in the USA, there has been an increase in invasive and non-invasive pneumococcal disease, and nasopharyngeal carriage, with serotype 19A Such data support the lack of efficacy of PCV7 against this serotype. We have not emphasized the PCV7 serogroup coverage in our analysis, but based on the bacteraemia study ( ), it was 85% in children 5 years and 58.9% for the total population. For the respiratory study, the level of serogroup coverage was 61% in children 5 years and 57.8% for the total population. One important limitation of our studies is the low proportion of children 5 years compared with the total population. Serotype 19A isolates obtained from a respiratory surveillance study in the USA were found to be clonal, increasing rapidly in prevalence and multidrug-resistant including highlevel penicillin-resistant and third-generation cephalosporinresistant. 32 Data from the USA indicate that invasive pneumococcal disease caused by multidrug-resistant serotype 19A is increasing and of great concern. 33 In our studies and the meta-analysis of Hausdorff et al., 24 the low PCV7 coverage of older children and adults is of concern, as it has been recently shown that the serotype 19A clone that is evolving rapidly in children after the introduction of PCV7 in the USA is also increasing in prevalence in all age groups (although at a slower rate than in children). 34 The significant and rapid increase in the prevalence of serotype 1 in our bacteraemia study is of great concern. This trend has recently been reported by the HPA, where an increase from 4% in to 13% in was noted in invasive disease, and the present data support this observation. 35 Serotype 1 isolates were relatively uncommon in the USA and in many developed countries in the few years running up to the formulation and introduction of PCV7, and hence this serotype was not included in PCV7. 36 However, this has not always been the case. In a meta-analysis of 13 studies in adults and 19 studies in children, covering the period , the proportion of serogroups 1 3 and 5 decreased from 71% to 7% and from 18% to 2% in adults and children, respectively. 37 Although the reasons for this are multifactorial, the introduction of antibiotics during this period is high on the list of potentially relevant factors. 37 It has been shown that serotype 1 isolates are hypervirulent and have a propensity to cause bacteraemic disease. 36 For example, between 1992 and 1997 in Sweden, the prevalence of serotype 1 increased from 1% to 10% and was found to be due to a ii93

8 Farrell et al. Table 8. Non-susceptibility by PCV7 coverage Bacteraemia study Respiratory study PCV7 serotypes non-pcv7 serotypes P value PCV7 serotypes non-pcv7 serotypes P value Ciprofloxacin a Cefotaxime Cefuroxime b , Erythromycin , , Penicillin , , Tetracycline a Resistance for ciprofloxacin. b Cefuroxime was tested in the respiratory study only. hypervirulent clone that resulted in an increasing incidence of bacteraemic disease during that period. 38 Clearly, we need to monitor the progress of serotype 1 in the UK and Ireland, and a most important immediate investigation would be to determine whether the isolates are genetically related. The increasing prevalence of serotype 1 will also be an important factor to consider in the development of new vaccines and for regulatory decision makers when assessing new vaccines that may already be in submission to the regulatory process. The incidence of invasive pneumococcal disease due to PCV7 serotypes among children eligible for vaccination in England and Wales has decreased notably in , i.e. shortly after the introduction of PCV7 in September 2006, 10 as also witnessed in the USA since vaccine introduction. It is important to note that this decrease was only noted after our studies, and hence the impact of the vaccine introduction will not bias our data. Early data suggest a small increase in invasive pneumococcal disease caused by non-vaccine serotypes in the 0 2 year age group. 39 It will be interesting to monitor the prevalence of antimicrobial nonsusceptibility in the non-vaccine serotypes. An increase in antimicrobial resistance was found in non-vaccine serotypes in the USA after the introduction of PCV7 with a multidrug-resistant serotype 19A clone being mostly responsible. 15 Most serotype 1 isolates are broadly susceptible to most antimicrobials, and it would be expected that the already increasing prevalence would be augmented by PCV7 utilization. If serotype replacement with predominantly serotype 1 occurs, we hypothesize that a decrease rather than increase in antimicrobial resistance would therefore follow. Unfortunately, this scenario may also result in the higher incidence of a hypervirulent pneumococcal population. Close and timely monitoring and reporting of pneumococcal epidemiology are therefore imperative. In summary, data from both the BSAC bacteraemia and respiratory surveillance studies show that antimicrobial nonsusceptibility rates were below average when compared globally. Moreover, for each study, there was no convincing evidence of a trend in non-susceptibility over time. The distribution of serotypes suggested that although PCV7 would provide adequate coverage of invasive isolates in the UK and Ireland, there was a significant and rapid increase of serotype 1 over the 6 years of the bacteraemia study. It will be interesting and very important to monitor both antimicrobial non-susceptibility and serotype distribution in the coming years. It is hoped that this and future data will be of assistance in establishing empirical treatment guidelines and optimal vaccination policies in the UK and Ireland. Acknowledgements We are grateful to all who have contributed to the success of the BSAC Resistance Surveillance Project, in particular, to the many laboratories that have collected isolates and all who have played a part in testing them [see page ii10 (Acknowledgements)]. Additional information on the isolates collected in the Project is available on the BSAC surveillance web site ( or through a link on the BSAC homepage See page ii12 (Publications) for a full list of previous publications from the Project, some of which may include parts of the information presented here. Funding The BSAC Resistance Surveillance Programmes up to 2006 (bacteraemia) and 2006/07 (respiratory) have received financial support from Abbott, AstraZeneca, Aventis, Basilea, Bayer, Cubist, GeneSoft, GlaxoSmithKline, Johnson & Johnson, Merck Sharp & Dohme, Novartis, Pfizer, Theravance, Wyeth or their predecessors. The BSAC funds the work of the Resistance Surveillance Coordinator (R. R.) and Resistance Surveillance Working Party. Transparency declarations This article is part of a Supplement sponsored by the British Society for Antimicrobial Chemotherapy. D. J. F. and D. F. have accepted grants, speaking invitations, conference invitations and have participated in advisory boards from most major pharmaceutical companies. D. M. L. has shareholdings in AstraZeneca, Pfizer, Schering Plough and GlaxoSmithKline and has accepted grants, speaking invitations and conference invitations from most major pharmaceutical companies. R. C. G. has received grant funding and/or speaking and conference invitations from Wyeth and GSK on vaccine-related topics. Both D. M. L. and R. C. G. are also employed within the UK public sector and are influenced by the HPA s views of antibiotic prescribing and usage. All other authors have none to declare. References 1. Melegaro A, Edmunds WJ, Pebody R et al. The current burden of pneumococcal disease in England and Wales. J Infect 2006; 52: ii94

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