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Conference Paper

Antibacterial usage in English NHS hospitals as part of a national Antimicrobial Stewardship Programme* J. Cooke a,b,*, P. Stephens c, D. Ashiru-Oredope d, A.P. Johnson d, D.M. Livermore d,e, M. Sharland f, on behalf of the Antimicrobial Stewardship Sub-Group of the Department of Health's Advisory Committee for Antimicrobial Resistance and Healthcare Associated Infectiong a

The Centre for Infection Prevention and Management, Division of Infectious Diseases, Department of Medicine, Imperial College London, UK b Faculty of Medical and Human Sciences, University of Manchester, UK c IMS Health, 210 Pentonville Road, London N1 9JY, UK d Centre for Infectious Disease Surveillance and Control, Public Health England, Colindale, London NW9 5EQ, UK e Norwich Medical School, University of East Anglia, Norwich, UK f Paediatric Infectious Diseases Unit, St George's Hospital, London, UK

article info

abstract

Article history:

Antimicrobial resistance (AMR) has become a global problem for health care services, with

Accepted 27 June 2014

fewer antimicrobials entering the market and some pathogenic organisms becoming

Available online 15 August 2014

resistant to commonly used antimicrobials. Antimicrobial stewardship (AS), including evidence-based standard setting, education and communication, and audits of practice,

Keywords:

has become a key method of preventing the rise in the rise in AMR. Data on antibiotic

Antibacterials

consumption are often obtained through prospective and retrospective point prevalence

Antibiotics

audits of antibiotic usage, but such studies are very resource intensive and only provide a

Antimicrobial stewardship

snapshot of consumption. The objective of the study reported here was to examine lon-

Hospital usage

gitudinal total antibacterial usage at a national level and cross-sectional usage at an individual hospital trust level using a commercial database that captures antimicrobial prescribing from at least 99% of English hospital Trusts. © 2014 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

*

This paper is based on material that was presented at the Public Health England Annual Conference 2013. * Corresponding author. The Centre for Infection Prevention and Management, Division of Infectious Diseases, Department of Medicine, Imperial College London, UK. E-mail address: [email protected] (J. Cooke). g A full list of members of the Antimicrobial Stewardship Sub-Group of the Department of Health's Advisory Committee for Antimicrobial Resistance and Healthcare Associated Infection who have supported the development of the paper, and their transparency declarations, appears in Appendix 1 at the end of the paper. http://dx.doi.org/10.1016/j.puhe.2014.06.023 0033-3506/© 2014 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

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Background

Results

Antimicrobial resistance (AMR) has become a global problem for health care services, with fewer antimicrobials entering the market and some pathogenic organisms becoming resistant to commonly used antimicrobials.1 Antimicrobial stewardship (AS), including evidence-based standard setting, education and communication, and audits of practice, has become a key method of preventing the rise in AMR.2 Over the past 10 years, the UK has seen a number of national initiatives to promote AS and address the rise in AMR. Examples include Essential Steps to Safe, Clean Care: Reducing Healthcare-Associated Infections3; Saving Lives4; The SACAR Antimicrobial Framework5; Clostridium difficile Infection: How to deal with the Problem6; Clean, Safe Care: Reducing Infections and Saving Lives 7; The Health and Social Care Act 2008, Code of Practice8; Start SMART then FOCUS9 and the UK Five-Year Antimicrobial Resistance Strategy.10 Although the importance of measuring antimicrobial consumption has repeatedly been highlighted, particularly in secondary care, the ability to undertake such analysis has been hampered by the lack of readily available data and, until recently, analysis of antibiotic acquisition costs has been the only way to estimate usage. Electronic prescribing (EP) and electronic medicines administration have the potential to provide better data, with patient-linked information on antimicrobial selection linked to diagnosis, microbiological results and outcomes. But fewer than 10% of English NHS hospitals have EP in place. Moreover, among hospitals that have implemented EP, there is a lack of standardized data husbandry. Data have also been obtained through prospective and retrospective point prevalence audits of antibiotic usage,11,12 but such studies are very resource intensive and only provide a snapshot of consumption. The objective of the study reported here was to examine longitudinal total antibacterial usage at a national level and cross-sectional usage at an individual hospital trust level using a commercial database that captures antimicrobial prescribing from at least 99% of English hospital trusts.

Longitudinal analysis The five-year trend in total antibacterial use in English hospitals between 2008 and 2012 is shown in Fig. 1. There was a 4$1% increase in total usage over this time period. Fig. 2 shows the changes in groups of antibacterials. There was a marked increase in the use of co-amoxiclav (þ56$6%) (Fig. 3) and a reduction in the use of flucloxacillin (15$2%) and, aminopenicillins, (amoxicillin and ampicillin: 12$6%). Fig. 4 shows the reduction in the use of cephalosporins with a fall in first-generation cephalosporins (cefadoxil, cefalexin and cefradine: 40$7%), second-generation cephalosporins (cefaclor and cefuroxime: 54$7%) and third generation cephalosporins (cefixime, cefotaxime, cefpodoxime, ceftazidime and ceftriaxone: 4$3%). There was also a fall in fluoroquinolones, mainly oral ciprofloxacin (23$8%). Counterbalancing these reductions, there was a substantial increase in the use of carbapenems (94$8%), mainly meropenem (Fig. 5), and also in the use of broad-spectrum antipseudomonal penicillins, particularly piperacillin/tazobactam (142$3%) (Fig. 6).

Fig. 1 e Total use of antibacterials in English hospitals n ¼ 165.

Method Hospital pharmacies in England provide aggregate monthly data on all medicines issued to patients, wards and clinics to IMS ((http://www.imshealth.com), a leading provider of information, services and technology for the health care industry), through an agreement that reimburses the hospital trusts for these data. As well as in-patient prescribing, IMS data also include outpatient prescribing from hospitals, genitourinary medicine (GUM) clinics and other prescribing to ambulatory patients. Occupied Bed-Days (OBD) data were obtained from Hospital Episode Statistics (http://www.hscic. gov.uk/hes). Data on issues of antimicrobials to wards, clinics and so on were converted to WHO Defined Daily Doses (DDDs).13 Where DDD data were not available then Average Daily Quantities (ADQ) were used (http://www.hscic.gov.uk/ media/9376/Average-daily-quantity-ADQ-values-2012-13/ pdf/adqs_2012_13.pdf).

Fig. 2 e Antibacterial usage for English hospitals n ¼ 165.

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Fig. 3 e Co-amoxiclav usage in Defined Daily Doses for English hospitals n ¼ 164. Fig. 6 e Antipseudomonal penicillin usage for English hospitals n ¼ 165.

lines describing the 75th percentile of the population of hospitals, revealing little general relationship though with a few outliers having high use of both classes.

Discussion Fig. 4 e Cephalosporin usage English hospitals n ¼ 165.

Cross sectional usage of antibacterials in 2011e12 The usage of antibacterials across all English NHS hospitals e corrected for annualised activity per 1000 occupied bed days showed considerable heterogeneity (Fig. 7). This wide general variation and, more specifically, the considerable variation in carbapenems as a proportion of trusts' total usage, offer further opportunities for analysis (Fig. 8). The relationship between the consumption of cephalosporins and fluoroquinolones is shown in Fig. 9, with horizontal and vertical

Fig. 5 e Carbapenem usage for English hospitals n ¼ 165.

Such a small increase in total antibacterial use would not be expected as, during this five-year period, there was an increase in patient throughput of over 17%. By contrast, the reduction in the usage of cephalosporins and quinolones is unsurprising, as a number of national initiatives have focussed on reducing the numbers of Clostridium difficile infections (CDI).6 There are national and local targets for CDI reduction to which all hospital trusts must agree and many sites have sought to meet these by addressing the use of antibiotic classes particularly associated with the selection of C. difficile, such as cephalosporins. The reductions in the use of cephalosporin and fluoroquinolone follow on from observations made in previous years when considerable reductions in the usage of these agents were already being recorded.14

Fig. 7 e Total antibacterial usage in English hospital trusts for 2011e12 n ¼ 163 DDDs per 1000 OBDs.

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Comparison with other countries shows that antibiotic usage in England is greater than in France16 and Australia.17 It is difficult to compare with antibiotic use in US hospitals as they do not use the same usage units.18 A confounder is that the English data include out-patient (ambulatory) usage which is not included in hospital data by other groups. Clearly, more work is required to validate these findings, but they illustrate an opportunity for hospitals to benchmark themselves against other similar units. Such benchmarking might prove a useful marker of antimicrobial stewardship. The new national programme, the English Surveillance Programme for Antimicrobial Utilization and Resistance (ESPAUR), led by Public Health England will work to ‘bring together the elements of antimicrobial utilization and resistance surveillance in both primary and secondary care settings, alongside the development of quality measures and methods to monitor unintended outcomes of antimicrobial stewardship and both public and professional behaviour interventions’.17

Fig. 8 e Carbapenem usage as % of total use of antibacterial in 165 English hospital trusts in 2011e2012.

Clearly, when there is a reduction in the use of one group of antibacterials there is often a corresponding increase in the use of others. In this case, a nearly 60% increase in co-amoxiclav use was observed. Of even greater concern was the marked increase in the use of anti-pseudomonal penicillins and carbapenems; these shifts are disturbing, particularly when there are global concerns about the increase in carbapenemaseproducing pathogens, which are resistant to these agents.15 The marked heterogeneity of antibacterial use between different English hospitals seen in the cross-sectional analysis is of particular interest. This heterogeneity might be explained by differences in hospital specialities. Hospitals that have a similar mix of medical and surgical specialties would be expected to have similar proportions of antibacterial usage, unless there were differences in the levels of antimicrobial stewardship between hospitals. By contrast, those hospitals that have certain specialties, such as cystic fibrosis, cancer or renal units, might be expected to show different patterns of usage.

Conclusion Longitudinal analysis of antimicrobial consumption offers a useful instrument for observing trends in consumption time for individual hospitals, groups of hospitals or whole countries. Cross-sectional analysis of usage between hospitals within defined time periods can be helpful in benchmarking usage within countries. Both methods are essential for informing antimicrobial stewardship programmes.

Author statements Ethical approval There was no requirement for any Ethical Approval.

Funding No funding of any kind has been received for this work.

Competing interests See Appendix 1.

references

Fig. 9 e Relationship between fluoroquinolones and cephalosporins in English NHS trust hospitals in 2011e12.

1. WHO Advisory Group on Integrated Surveillance of Antimicrobial Resistance (AGISAR). Antimicrobial resistance: global report on surveillance 2014; April 2014. 2. Cooke J, Alexander K, Charani E, Hand K, Hills T, Howard P, Jamieson C, Lawson W, Richardson J, Wade P. Antimicrobial stewardship: an evidence-based, antimicrobial selfassessment toolkit (ASAT) for acute hospitals. J Antimicrob Chemother 2010;65(12):2669e73. 3. Department of Health. Essential steps to safe, clean care: reducing healthcare-associated infections the delivery programme to reduce healthcare associated infections (HCAI) including MRSA. London: Crown; 2006.

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4. Department of Health. Saving lives: reducing infection, delivering clean and safe care. London: Crown; 2007. 5. Cooke J, Garner S, Finch Ron behalf of the Special Advisory Committee on Antimicrobial Resistance (SACAR). Specialist advisory committee on antimicrobial resistance (SACAR) antimicrobial framework. J Antimicrob Chemother 2007;60:i87e90. 6. Department of Health and the Health Protection Agency. Clostridium difficile infection: how to deal with the problem. London: Department of Health; 2008. 7. Department of Health. Clean, safe care: reducing infections and saving lives. London: Crown; 200840. 8. Department of Health. The health and social care act 2008; 2008. 9. Department of Health Advisory Committee on antimicrobial resistance and healthcare associated infection (ARHAI) 1. Antimicrobial stewardship: “Start Smart, e then Focus” guidance for antimicrobial stewardship in hospitals (England). London: Health Do; 2011. 10. Department of Health. UK 5 year antimicrobial resistance strategy 2013 to 2018. London: Department of Health; 2013. 11. Aldeyab M, Kearney MP, McElnay JC, Magee FA, Conlon G, Gill D, Davey P, Muller A, Goossens H, Scott MG. A point prevalence survey of antibiotic prescriptions: benchmarking and patterns of use. Br J Clin Pharmacol 2011;71:293e6. 12. Health Protection Agency. English national point prevalence survey on healthcare-associated infections and antimicrobial use; 2011. 13. WHO Collaborating Centre for Drug Statistics Methodology. ATC/DDD index e international language for drug utilization research. WHO Collaborating Centre for Drug Statistics Methodology; 2014. 14. Ashiru-Oredope DSM, Charani E, McNulty C, Cooke Jon behalf of ARHAI Antimicrobial Stewardship Group. Improving the quality of antibiotic prescribing in the NHS by developing a new Antimicrobial Stewardship Programme: Start SmartdThen Focus. J Antimicrob Chemother 2012;67:i51e63. 15. Nordmann P, Naas T, Poirel L. Global spread of carbapenemase producing enterobacteriaceae. Emerg Infect Dis 2011;17:1791e8. 16. Dumartin C, L'Heriteau F, Pefau M, Bertrand X, Jarno P, Boussat S, Angora P, Lacave L, Saby K, Savey A, Nguyen F, Carbonne A, Rogues AM. Antibiotic use in 530 French hospitals: results from a surveillance network at hospital and ward levels in 2007. J Antimicrob Chemother 2010;65(9):2028e36. 17. Rajmokan M, Morton A, Marquess J, Playford EG, Jones M. Development of a risk-adjustment model for antimicrobial utilization data in 21 public hospitals in Queensland, Australia (2006e11). J Antimicrob Chemother 2013;68:2400e5. 18. Polk RE, Hohmann SF, Medvedev S, Ibrahim O. Benchmarking risk-adjusted adult antibacterial drug use in 70 US academic medical center hospitals. Clin Infect Dis 2011;53:1100e10.

Appendix 1

Acknowledgements The following co-authors helped to support the development of the paper through the Antimicrobial Stewardship subcommittee of the Department of Health's Advisory Committee for Antimicrobial Resistance and Healthcare Associated Infection (ARHAI) and the Specialist Advisory Committee for Antimicrobial Resistance (SACAR). Esmita Charani MSc Inf Dis The Centre for Infection Prevention and Management, Division of Infectious Diseases, Department of Medicine, Imperial College London.

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Matthew Dryden MD, Director of Infection Prevention and Control, Royal Hampshire County Hospital, Winchester. Carole Fry, Nurse Advisor, Communicable Diseases, Department of Health (England), Infectious Diseases and Blood Policy Branch, Department of Health, London. Kieran Hand PhD, Consultant Pharmacist Anti-Infectives, University Hospital Southampton NHS Foundation Trust, Southampton. Paula Mansell RGN, National Advisor for Healthcare Associated Infections, The Care Quality Commission, Finsbury Tower, 103-105 Bunhill Row, London, EC1Y 8TG. Cliodna McNulty, Head, Health Protection Agency Primary Care Unit.4 Sally Wellsteed, Team Leader Infection Control.6 Alison Holmes MD, Professor in Infectious Diseases, The Centre for Infection Prevention and Management, Division of Infectious Diseases, Department of Medicine, Imperial College London. Philip Howard BPharm, Consultant Antimicrobial Pharmacist, Leeds Teaching Hospitals NHS Trust, Leeds.

Transparency declarations JC Chaired the Antimicrobial Stewardship Sub-Group of the Department of Health Advisory Committee on Antimicrobial Resistance and Healthcare Associated Infection. (Travel expenses only). Has Chaired, presented and received honoraria at meetings supported by Astellas, HHI and Alere. Honoraria received. PS e Is employed by IMS Health. IMS Health provides information services to the pharmaceutical industry and governments, including the manufacturers of antibiotics and the Department of Health. DAO e none declared. EC e none declared. MD e none declared. CF e none declared. KH e Occasional consultant to Astellas, MSD and AstraZeneca. AH e none declared. PH e none declared. APJ is Editor-in-Chief of the Journal of Antimicrobial Chemotherapy. DML is partly self-employed and consults for numerous pharmaceutical and diagnostic companies, including Achaogen, Adenium, Allecra, Astellas, AstraZeneca, Bayer, Basilea, bioMerieux, Cubist, Curetis, GSK, Kalidex, Merck, Meiji Seika, Pfizer, Roche, Tetraphase and Wockhardt; he holds grants from Basilea, Cubist, Meiji Seika, Merck; has received lecture honoraria or travel reimbursement from AstraZeneca, Curetis, GSK, J&J, Merck, Novartis, Pfizer and Tetraphase and holds shares in Dechra, Eco Animal Health, GSK, Merck and Pfizer, collectively amounting to

Antibacterial usage in English NHS hospitals as part of a national Antimicrobial Stewardship Programme.

Antimicrobial resistance (AMR) has become a global problem for health care services, with fewer antimicrobials entering the market and some pathogenic...
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