Dilip Nathwani
email: dilip.nathwani@nhs.net

Jacqueline Sneddon

William Malcolm

Camilla Wiuff

Andrea Patton

Simon Hurding

Anne Eastaway

R Andrew Seaton

Emma Watson

Elizabeth Gillies

Peter Davey

Marion Bennie

Scottish Antimicrobial Prescribing Group (SAPG): development and impact of the Scottish National Antimicrobial Stewardship Programme

Keywords:

In 2008, the Scottish Management of Antimicrobial Resistance Action Plan (ScotMARAP) was published by the Scottish Government. One of the key actions was initiation of the Scottish Antimicrobial Prescribing Group (SAPG), hosted within the Scottish Medicines Consortium, to take forward national implementation of the key recommendations of this action plan. The primary objective of SAPG is to coordinate and deliver a national framework or programme of work for antimicrobial stewardship.

The European perspective

In 2008, sixteen countries in Europe developed a national strategy to contain antimicrobial resistance [START_REF] Monnet | Turning the tide of antimicrobial resistance: Europe shows the way[END_REF]. Many countries in Europe had reported a successful reduction in antibiotic resistance in specific areas, but this strategy described a comprehensive approach to tackling the problem [START_REF] Monnet | Turning the tide of antimicrobial resistance: Europe shows the way[END_REF].

In 2008 [START_REF] Mölstad | Sustained reduction of antibiotic use and low bacterial resistance: 10-year followup of the Swedish Strama programme[END_REF], the Swedish Strategic Programme for the Rational Use of Antimicrobial Agents and Surveillance of Resistance (STRAMA) project reported a sustained reduction in antibiotic use and low bacterial resistance rates after a 10-year follow-up period, but without any measurable negative consequences. This multidisciplinary, co-ordinated programme supported by the Swedish Government since 2000 has demonstrated that antibiotic use can be reduced without any measurable unintended harm. Key to the Swedish model appeared to be a multidisciplinary national steering group, with primarily a co-ordinating role, and regional groups functioning at county level that implemented a range of stewardship activities supported by comprehensive data on antibiotic use and surveillance of antimicrobial resistance.

We believed that the organisation, structure and delivery of health care in Scotland had many similarities to Sweden and thereby would allow us to adopt and adapt core components of STRAMA. Sweden has a population of ca. 11 million and health care is provided via 21 county-based services, whilst Scotland has a population of 5.1 million (8% of the UK population) with healthcare delivered via 14 regional National Health Service (NHS) boards. The budget and management of health is devolved to the Scottish Parliament and the national healthcare system provides hospital and The Welsh Antimicrobial Resistance Programme [START_REF]About the Welsh Antimicrobial Resistance Programme[END_REF], established in 2005, provides similar information to STRAMA on national and regional data regarding antimicrobial use and resistance. A delegation from Scotland visited the Welsh Surveillance Unit in Cardiff to learn how prescribing and surveillance data are collected and evaluated.

The Scottish context

In 2008, The Scottish Management of Antimicrobial Resistance Action Plan (ScotMARAP) was published by the Scottish Government (http://www.scotland.gov.uk/Publications/2008/03/12153030/0). One of the key actions was initiation of the Scottish Antimicrobial Prescribing Group (SAPG), hosted by the Scottish Medicines Consortium (SMC), to take forward national implementation of the key recommendations of this action plan. The primary objective of SAPG is to co-ordinate and deliver a national antimicrobial stewardship programme. SAPG was initiated in March 2008, initially for a period of 3 years, and was supported by central funding from the Scottish Government Health Department.

In convening SAPG, we tailored the structure and operational model to reflect local existing and emergent problems as well as local geographical and staffing structures. Whilst complementing many of the strengths of STRAMA and the Welsh programme, we have also introduced some unique or novel approaches and measures.

A c c e p t e d M a n u s c r i p t

For NHS Scotland, reducing harm from healthcare-associated infections (HAIs) has been a high priority since 2005 and national programmes to address HAIs have been co-ordinated by the Scottish Government HAI Task Force. The importance of integrating HAI within a quality strategy or framework has been recognised by guidance from the European Union [START_REF] Allerberger | Antibiotic stewardship implementation in the EU: the way forward[END_REF] and elsewhere [START_REF] Owens | Antimicrobial stewardship: concepts and strategies in the 21st century[END_REF] and is reflected within the Healthcare Quality Strategy published in 2010 (http://www.scotland.gov.uk/Resource/Doc/311667/0098354.pdf; accessed 22 November 2010).

As part of the HAI Delivery Plan 2005-2008, a national survey of HAI prevalence (http://www.documents.hps.scot.nhs.uk/hai/sshaip/publications/national-prevalencestudy/report/full-report.pdf; accessed 22 November 2010) undertaken between October 2005 and October 2006 indicated an overall prevalence of 9.5% for acute hospitals and 7.3% for non-acute hospitals. In this survey, prescription of antimicrobials was also examined as a potential proxy indicator for HAI. However, whilst local hospitals were able to collect some information in relation to the quantity and quality of antibiotic prescribing, there was no robust national validated system for measuring this. A single point-prevalence survey of antimicrobial prescribing was also performed in 10 Scottish hospitals using the Glasgow Antimicrobial Audit Tool (GAAT) [START_REF] Seaton | Point prevalence survey of antibiotic use in Scottish hospitals utilising the Glasgow Antimicrobial Audit Tool (GAAT)[END_REF] to give more qualitative information about the quality of prescribing within a representative sample of acute Scottish hospitals. Results from this study showed that of 3826 patients surveyed, 1079 (28.2%) received an antibiotic, 381 (35.3%) intravenously; 197 patients (28.2%) treated orally had prior intravenous therapy.

Third-generation cephalosporins (28.3%) were the most frequently used antibiotics, followed by amoxicillin/clavulanic acid (co-amoxiclav) (20.2%), metronidazole

Organisation of SAPG

National level

The SAPG programme is delivered through a hub and spoke model (as shown in SAPG has also established a network of AMTs that meet three times a year to discuss current national and local issues and to share good practice in antimicrobial stewardship. The agenda and direction of the network events is owned by AMTs with administrative support from SAPG. The impact of this network is powerful in terms of developing local leadership, ownership of the projects, cohesion, learning and supporting implementation at a team and personal level. Evaluation of each of the events has been very good and provides not only areas for improvement but also ensures that the content of future network events addresses the needs of the AMTs.

Regional level

AMTs are subgroups of NHS board Area Drug and Therapeutics Committees (ADTCs) and they should report to the NHS board Executive Team via the Medical Director.

The minimum constituents of an AMT are a lead clinician, lead infection specialist and lead antimicrobial pharmacist plus additional members depending on local resources [START_REF] Dellit | Infectious Diseases Society of America; Society for Healthcare Epidemiology of America. Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship[END_REF]8]. The evidence to support the effectiveness of a variety of stewardship tools has also been subjected to systematic review [START_REF] Dellit | Infectious Diseases Society of America; Society for Healthcare Epidemiology of America. Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship[END_REF][START_REF] Davey | Systematic review of antimicrobial drug prescribing in hospitals[END_REF][START_REF] Arnold | Interventions to improve antibiotic prescribing practices in ambulatory care[END_REF], the last two [START_REF] Davey | Systematic review of antimicrobial drug prescribing in hospitals[END_REF][START_REF] Arnold | Interventions to improve antibiotic prescribing practices in ambulatory care[END_REF] of which are currently being updated. Some additional national non-recurring resource was made available by the Scottish Government Health Department to support the

SAPG workstreams

The work plan and fiscal requirements for SAPG were developed and articulated through a project initiation model with actions organised into five workstreams. These workstreams were developed to reflect national and local unmet needs and priorities. The intention was that they would be dynamic and would change with the evolution of SAPG and priorities in HAI to meet new challenges. At the heart of this work was a strongly held philosophy that we must be able to measure the impact of our interventions and that this would be supported by a mechanism of sharing data in a timely and appropriate manner. The workstreams have vertical and horizontal integration to achieve the goals outlined previously and each is led by an expert in the specific area. Much of the work is ongoing, and following a recent strategic A c c e p t e d M a n u s c r i p t review of the 3-year work plan there will be a redesign of this structure as we embark on the next phase of our work plan in April 2011. This future work is described later.

Here we report the development of this work and some early outcomes.

Organisation and accountability

This work, led by the HAI team, NHS QIS, involves working with NHS boards to ensure that essential organisational and accountability infrastructures relevant to antimicrobial stewardship are in place. A self-assessment questionnaire was developed and completed by all NHS boards in December 2008 to establish a baseline position for antimicrobial stewardship within each NHS board. A similar tool developed in England has recently been published [START_REF] Cooke | Antimicrobial stewardship: an evidence-based, antimicrobial self-assessment toolkit (ASAT) for acute hospitals[END_REF] that provides a web-based tool to assess longitudinal progress on stewardship in acute hospitals or potentially to act as a benchmark with similar organisations.

Our baseline survey showed that all NHS boards now have an established AMT (of varying composition and activity) and all have an antimicrobial pharmacist or specialist pharmacist input, all AMTs report to the NHS board Medical Director and the ADTC, but links vary with other key groups such as the IPCT and clinical governance and risk management.

Infection management

This work focuses on development of a national approach to antimicrobial prescribing policies, quality indicators for prescribing in all healthcare settings, and clinical audit of infection management. This workstream is supported by a variety of healthcare professionals from around Scotland, and several subgroups have been established to lead on topics including Primary Care, Surgical Prophylaxis, Care Homes, and Public Campaigns.

One of the immediate public health challenges for SAPG was the high incidence of CDI in Scottish hospitals and the emerging problem of community-onset CDI. The contribution of antibiotics, particularly certain classes (cephalosporins, co-amoxiclav, clindamycin and quinolones), which we have termed 'C. diffogenic' agents (CDAs), to the current epidemic of CDI has been recognised from a variety of studies [START_REF] Rice | The Maxwell Finland Lecture: for the duration-rational antibiotic administration in an era of antimicrobial resistance and Clostridium difficile[END_REF][START_REF] Song | Rising economic impact of Clostridium difficile-associated disease in adult hospitalized patient population[END_REF][START_REF] Pépin | Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile-associated diarrhea: a cohort study during an epidemic in Quebec[END_REF][16][START_REF] Barbut | European Study Group on Clostridium difficile (ESGCD). Prospective study of Clostridium difficile infections in Europe with phenotypic and genotypic characterisation of the isolates[END_REF][START_REF] Carignan | Risk of Clostridium difficile infection after perioperative antibacterial prophylaxis before and during an outbreak of infection due to a hypervirulent strain[END_REF]. This information and evidence linking the high-level impact of antibiotic restriction combined with strict infection control measures in controlling hospital CDI outbreaks [START_REF] Fowler | Successful use of feedback to improve antibiotic prescribing and reduce Clostridium difficile infection: a controlled interrupted time series[END_REF][START_REF] Weiss | Multipronged intervention strategy to control an outbreak of Clostridium difficile infection (CDI) and its impact on the rates of CDI from 2002 to 2007[END_REF][START_REF] Power | Reducing Clostridium difficile infection in acute care by using an improvement collaborative[END_REF][START_REF] Aldeyab | Quasiexperimental study of the effects of antibiotic use, gastric acid-suppressive agents, and infection control practices on the incidence of Clostridium difficile-A c c e p t e d M a n u s c r i p t associated diarrhea in hospitalized patients[END_REF][START_REF] Vernaz | Temporal effects of antibiotic use and Clostridium difficile infections[END_REF] supported the development and implementation of national guidance on restriction of CDA antibiotics. Our first national guidance document was (http://www.scottishmedicines.org.uk/SAPG/Scottish_Antimicrobial_Prescribing_Gro up__SAPG_). These guidance documents recommended a variety of minimum good practice measures previously published [8] and encouraged the use of narrowspectrum agents for the empirical management of infection and surgical prophylaxis [START_REF] Carignan | Risk of Clostridium difficile infection after perioperative antibacterial prophylaxis before and during an outbreak of infection due to a hypervirulent strain[END_REF], but were suitable for local adaptation where appropriate. One of the key new recommendations was around antibiotic use and risk of CDI. All NHS boards have now reviewed their hospital antibiotic policies to ensure that the use of CDAs is restricted both for treatment of infections and in surgical prophylaxis. Implementation of these antimicrobial stewardship measures has been staggered over a period of ca. 18 months, with some NHS boards acting as early adopters of our guidance, but there is now uniformity of approach across all the boards. Furthermore, national consensus guidance was also developed and implemented to reduce variation around the use and monitoring of key antibiotics, vancomycin and gentamicin, because these agents featured significantly in the new hospital antibiotic policies for managing empirical sepsis and, in the case of gentamicin, surgical Similarly guidance on the management of infections in primary care based on the Health Protection Agency template and recommending restriction of CDAs has been adopted within all NHS boards, with implementation supported by prescribing advisers and primary care pharmacists working closely with AMTs and general practitioners. A range of indicators have been developed to measure the impact of implementation of primary care guidance and these will be discussed in the Information section.

Community-acquired pneumonia (CAP)

CAP remains the third commonest medical indication for hospitalisation in Scotland.

The Scottish National Audit Project-Community Acquired Pneumonia (SNAP-CAP), initiated by the Health Foundation Engaging with Quality programme, was taken over by SAPG in 2009 as an exemplary quality improvement model for infection management with a view to embedding this methodology within NHS boards. A care bundle comprising oxygen administration, severity assessment and prompt antibiotic treatment has been promoted as best practice in managing pneumonia in all NHS boards, focusing on Acute Medical Admissions Units. The data management system used for SNAP-CAP is the Extranet system provided by the Institute for Healthcare Improvement (IHI) (http://www.ihi.org/ihi/about), which provides a secure environment for data entry and viewing results. In addition, the Extranet is a single point for all project resources and an efficient method for communication between SAPG and the clinical teams and has also been developed and expanded to report A c c e p t e d M a n u s c r i p t national prescribing indicator data, which will be discussed later. The CAP project is beginning to show a good level of compliance with the care bundle and a consistent level of engagement in some areas of Scotland. Further data related to this project will be presented separately in the future.

Information

This work, led by NHS NSS, which comprises HPS and ISD, involves the development of systems for the collection, analysis and reporting of information relating to antimicrobial prescribing and resistance in all healthcare settings. A key objective is to align the surveillance of antimicrobial prescribing and resistance activity at local and national levels to support AMTs and frontline staff by allowing local access to standardised information that is relevant to their own practice, ward or clinical area across NHS boards in Scotland. The aim is to support NHS boards, AMTs and IPCTs in their strategic planning and in implementation and evaluation of antimicrobial stewardship and infection control measures aimed at minimising the evolution and spread of resistant pathogens, which will limit the harmful effect of these on the public. In addition, two national reports presenting combined antimicrobial use and antimicrobial resistance data for 2008 and 2009 have been produced (http://www.documents.hps.scot.nhs.uk/hai/amr/annual-report/2009-sapgamr-report.pdf).

Antimicrobial use

In Scotland, all antimicrobials for systemic use are classed as prescription-only medicines, which means that they can only be supplied in accordance with a A c c e p t e d M a n u s c r i p t prescription written by a doctor, dentist or other authorised prescriber. Information on the use of antibacterials in primary care is available within a database maintained by ISD and uses data from the Practitioner Services Division of NSS, which is responsible for the processing and pricing of all prescriptions dispensed in Scotland.

The normal convention is to present information on the use of antibacterials expressed as number of items per 1000 population in Scotland per day (items/1000/day) and as total defined daily doses (DDD) per 1000 population per day (DDD/1000/day). This allows comparison of usage over time as well as international comparison of the use of antibacterials presented using DDD. Care increased by 4.9% in 2009 compared with 2008. This is presented in Table 1.

One particular indicator, seasonal variation in quinolones use, has been adopted as a national prescribing target for quality of prescribing and will be discussed later.

Empirical prescribing of antibiotics for acutely unwell hospitalised patients and surgical prophylaxis were identified as likely key areas of variation and poor practice.

This was based on a small previous Scottish study [START_REF] Seaton | Point prevalence survey of antibiotic use in Scottish hospitals utilising the Glasgow Antimicrobial Audit Tool (GAAT)[END_REF] and data from participating This report confirmed areas of poor practice. Less than 60% of prescribers complied with local policy, in nearly one-quarter of medical records no indication was written in the notes, and nearly one-third of patients were given surgical prophylaxis for >24 h (see Table 2). Furthermore, the results of the PPS showed that almost 40% of antimicrobials used for surgical prophylaxis in Scotland were cephalosporins and, whilst use of antibiotics associated with a higher risk of CDI for treatment of infections was lower in Scotland compared with Europe, they still represented a significant burden of overall antibiotic consumption. These results provided SAPG and AMTs with useful information on the quality of prescribing within participating hospitals in Scotland and informed the priorities for quality improvement.

A c c e p t e d M a n u s c r i p t

In 2011, the national database of use of medicines in hospital will become available for the first time in Scotland. The Hospital Medicines Utilisation Database (HMUD) maintained by ISD will collect information from individual hospital pharmacy systems and will present standardised information on the use of medicines at NHS board and national levels via a web-based system. The first main clinical area to benefit from this new national information will be surveillance of the use of antimicrobials in the hospital setting. SAPG have developed a series of standard reports on hospital use of antimicrobials that are accessible within HMUD. This information will complement the information on primary care use of antimicrobials available in PRISMS.

Antibiotic resistance

In 2009, a national surveillance programme for monitoring antimicrobial resistance in clinically important pathogens was developed.

The Scottish surveillance programme is modelled on the European Antimicrobial Resistance Surveillance System (EARSS) and is initially focusing on monitoring antimicrobial resistance in invasive isolates from hospital patients with bloodstream

infections (caused by Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus faecium and Enterococcus faecalis).

A major achievement in 2009 was the standardisation of antimicrobial susceptibility testing of blood cultures. This was achieved, in collaboration with diagnostic microbiology laboratories in Scotland, by the implementation of VITEK 2 systems (an A c c e p t e d M a n u s c r i p t automated identification and antimicrobial susceptibility testing system) in laboratories across Scotland. The VITEK 2 system provides high quality and comprehensive comparable antimicrobial resistance information for all NHS boards in Scotland that will allow detailed analysis of resistance trends and emerging new resistances at national level. A key priority for 2011 is to develop further and to consolidate the standardisation of susceptibility testing in all NHS boards through testing and reporting via the VITEK 2 system. At the time of writing this report, ten Scottish diagnostic laboratories transfer VITEK 2 data directly to ECOSS (Electronic Communication of Surveillance in Scotland), which gives HPS access to the full data sets including phenotypic data on antimicrobial-pathogen combinations without omitting the suppressed susceptibility data (that normally are withheld for clinical reasons).

Overall there has been a large increase in reporting of Gram-negative bacteraemias from 2008 to 2009 as electronic reporting from diagnostic laboratories to HPS was fully implemented during this period. Given that reporting of bacteraemias to HPS was incomplete prior to 2009, we are not able to comment on whether there has been a true increase in the number of Gram-negative cases in this period.

Resistance to nearly all clinically important classes of antibiotics, including aminopenicillins, second-and third-generation cephalosporins, fluoroquinolones and aminoglycosides, was observed among the Gram-negative bacteraemia isolates. No to gentamicin is of particular concern and will be followed closely as this antibiotic is used increasingly in hospitals following the restriction in cephalosporin use. A further positive result was that combined resistance to third-generation cephalosporins and either fluoroquinolones or aminoglycosides decreased significantly in E. coli and P. aeruginosa (P < 0.05). Although resistance trends among the Gram-negatives are stable or decreasing for some antibiotics (and combinations of those), a different picture emerged when the data were analysed in line with the recent European expert guidance on standardisation of terminology of multidrug resistance [START_REF] Grundmann | Carbapenem-non-susceptible Enterobacteriaceae in Europe: conclusions from a meeting of national experts[END_REF]. In total, 16.6% of E. coli and 10.3% of K. pneumoniae isolates from 2009 could be categorised as multidrug-resistant (MDR), defined as resistant to at least three categories of antimicrobials with different mechanisms of actions. In a small number of isolates of E. coli and K. pneumoniae resistance was detected in up to eight antimicrobial categories. As not all isolates were tested against antibiotics of all categories, these figures could be underestimates of the true occurrence of multidrug resistance. These findings are worrying as a recent publication reported frequent identification of carbapenemase-producing Enterobacteriaceae (from the UK, India and Pakistan) that are extensively resistant to most available antibiotics [START_REF] Kumarasamy | Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study[END_REF] to 28% in 2009. This surveillance programme is in its infancy and so it is difficult to be certain that this is a true increase. None the less, vancomycin resistance in this organism continues to be a concern due to the fact that the resistance mechanism can be transferred to other pathogens (including MRSA). Despite promising trends in some areas, antimicrobial resistance remains a serious cause for concern, and new mechanisms of resistance are being reported, particularly the emergence of carbapenemases. E-learning resources have also been produced on bacterial resistance and CDI to provide continuing professional development opportunities for healthcare staff, and NES are monitoring their uptake and feedback evaluation. A recent 2010 review (Helen Maitland, pers. comm.) advised that 1148 learners had completed the CDI tutorial and in one NHS board all consultants were mandated to complete this, with 94% of them considering the tutorial to be useful in terms of impacting on their clinical practice. In total, 322 learners have completed the more recently available bacterial resistance tutorial and 98% stated its relevance to their clinical practice. The availability and increasing uptake of these educational resources is encouraging and for senior clinical staff, with the support of the Scottish Royal Colleges Academies, we are planning a range of focused educational activities to support their learning needs.

Education

Prescribing indicators to support reduction of Clostridium difficile infection

A priority area for the Scottish Government and SAPG is reducing CDI. A letter issued to NHS board chief executives [CEL 11 (2009) 3.

The prescribing indicators were developed by SAPG following broad consultation with specialists throughout Scotland, with two aimed at evaluating the quality of hospital prescribing (empirical treatment and surgical prophylaxis) and one aimed at primary care prescribing. The evidence to support these indicators, in the context described, has been recently reviewed [START_REF] Davey | Overview of strategies for overcoming the challenge of antimicrobial resistance[END_REF]. The indicators are either measurable from routinely available data or can be measured in a sustained way by clinical teams.

Hospital indicators

The two hospital prescribing target indicators for empirical prescribing and surgical prophylaxis were chosen to measure compliance with local antimicrobial policies.

SAPG had previously recommended review of all hospital antimicrobials to restrict

CDAs. Compliance with policy would therefore give assurance that restrictive policies had been effectively implemented. The antibiotic stewardship aim of ensuring effective treatment for patients with bacterial infection was achieved by aligning the hospital empirical prescribing indicator with measures for improving the quality of care for patients with pneumonia in Acute Medical Admissions Units [START_REF]Scottish Antimicrobial Prescribing Group (SAPG[END_REF] and by aligning the surgical prophylaxis indicator with measures for ensuring effective antibiotic prophylaxis in the SPSP [30].

A c c e p t e d M a n u s c r i p t

We used the IHI Extranet, which has been developed to support international quality improvement projects over more than 10 years [START_REF] Resar | Using a bundle approach to improve ventilator care processes and reduce ventilatorassociated pneumonia[END_REF] and was already being used by all NHS boards for both the SPSP [30] and the SAPG pneumonia work. Table 3 identifies the measures used to assess compliance with the hospital-based empirical prescribing. Data are collected in Acute Admission Units (medical and surgical) by sampling a recommended 20 patients per month per ward. Whilst the data collected are not formally quality assured in line with current practice within the SPSP and other IHI quality improvement initiatives, local AMTs are working with clinical staff to ensure the validity of the data. Compliance with the empirical prescribing policy is measured against the first antibiotic prescribed for a condition listed in the policy. The data for 2010 in Fig. 2 show a general improvement in compliance and recording in the notes compared with 2008 and 2009. These data cover the period September 2009 to September 2010. Approximately 7500 patients had been audited during this time and the overall compliance rate was 76%. However, the improvement is not consistent and reliable across all areas. To achieve a higher level of compliance, SAPG will support organisational and systems change through the existing quality improvement structures within boards.

These national results are reported every 3 months to the Scottish Government and a copy of the national report is sent to AMTs and NHS board Medical Directors along with their own board-level data for comparison. An example of this information is available in Table 4.

A c c e p t e d M a n u s c r i p t

Boards can agree to share data with each other and are also encouraged to share these data with clinical teams to drive quality improvement. The mechanisms for sharing these data and the degree of sharing are variable amongst boards. Ideally, all data in relation to HAIs should be owned, collected and shared by the clinical teams supported by infection prevention, AMTs and patient safety teams.

Frequently, these data are combined with infection prevention data and communicated jointly at educational and audit events for clinical teams. This cohesive working between teams with shared goals is the proposed steer for national collaboration and integration of quality improvement programmes.

A similar approach has been undertaken to collect data for surgical prophylaxis. Two components of the prophylaxis prescription, compliance with local policy and restricting duration to <24 h, are collected. It was suggested that this could be done initially for two common surgical procedures such as orthopaedics, vascular surgery or colorectal surgery. Local data from a variety of hospitals, collecting different procedures, show a variable level of compliance with local policy. We also are aware that some hospitals have not fully implemented the new restricted policy and are still using cephalosporin-based regimens in some specialties. Both measures (compliance and duration) are now being incorporated into the SPSP surgical checklist PAUSE [30] and a robust mechanism of collecting and reporting these data is presently being developed. These data will be used to support improvement in this area. Therefore, we presently do not have standardised reliable data on compliance with this target. Boards and SAPG presently rely on local AMT intelligence, through audit, to evaluate clinical practice. Further, streamlining of the key recommended A c c e p t e d M a n u s c r i p t procedures where collection of these data is mandatory will further facilitate engagement with collection of these data.

Primary care indicators

The primary care target (seasonal variation in quinolone use) has been suggested as a quality indicator by ESAC [START_REF] Ansari | The European Surveillance of Antimicrobial Consumption (ESAC) point-prevalence survey of antibacterial use in 20 European hospitals in 2006[END_REF][START_REF] Coenen | ESAC Project Group. European Surveillance of Antimicrobial Consumption (ESAC): quality indicators for outpatient antibiotic use in Europe[END_REF] and data are available to show substantial variation between NHS boards. The range of variation for this indicator across NHS boards in Scotland was greater than the range observed across European countries in ESAC primary care studies [START_REF] Coenen | ESAC Project Group. European Surveillance of Antimicrobial Consumption (ESAC): quality indicators for outpatient antibiotic use in Europe[END_REF].

Seasonal variation is defined as the increase in use of antibacterials during the two winter quarters (October-March) relative to use in the preceding two summer quarters (April-September). Fluoroquinolones are antibiotics that are not recommended for use within primary care, except for a few specific infections, and their inappropriate use has been associated with an increased risk of CDI, particularly the 027 and 106 strains, both of which are prevalent in Scotland [START_REF] Rice | The Maxwell Finland Lecture: for the duration-rational antibiotic administration in an era of antimicrobial resistance and Clostridium difficile[END_REF][START_REF] Pépin | Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile-associated diarrhea: a cohort study during an epidemic in Quebec[END_REF][START_REF] Sundram | Clostridium difficile ribotypes O27 and 106: clinical outcomes and risk factors[END_REF]. Excess usage of fluoroquinolones during the winter months suggests inappropriate use for respiratory infections.

The suggested indicator and target are that seasonal variation in the use of fluoroquinolones should be no more than 5% greater in the winter months compared with the preceding summer months. In Scotland this indicator has been made accessible as a standard report within PRISMS. Fig. 3 shows annual seasonal variation in the use of fluoroquinolones expressed as DDD/1000/day. This suggests that at a national level good progress has been made toward the Scottish

Impact on Clostridium difficile infection

Mandatory surveillance of CDI in patients aged ≥65 years showed a continuing decline in rates (per 1000 occupied bed-days) during 2009. Over the four quarters of 2009, the overall CDI rate dropped consecutively from 0.88 in Q1 to 0.77 in Q2, 0.66 in Q3 and 0.52 in Q4, for an overall decrease of 41% during 2009. This trend has continued into 2010 although the rate of decline appears to slowing (see Fig. 4).

Compared with 2008, the number of cases dropped 43% (6322 to 3625) and the overall rate for Scotland decreased by 42% (1.23 to 0.71). There is a temporal association between the introduction of restrictive antimicrobial policies in line with SAPG guidance and the declining rates of CDI in Scotland. However, it is difficult to quantify the true impact of this type of intervention separately from others that have been implemented concurrently to control and prevent CDI.

With the use of time series analysis [START_REF] Aldeyab | Quasiexperimental study of the effects of antibiotic use, gastric acid-suppressive agents, and infection control practices on the incidence of Clostridium difficile-A c c e p t e d M a n u s c r i p t associated diarrhea in hospitalized patients[END_REF][START_REF] Vernaz | Temporal effects of antibiotic use and Clostridium difficile infections[END_REF] we plan to quantify the true impact of

Unintended consequences

The changes in antimicrobial prescribing patterns caused by the introduction of the national antimicrobial stewardship programme are creating new selective pressures on the microbial flora found in humans and the environment both of hospitals and the community, and potentially cause new clinical problems, referred to as 'unintended consequences'. These include the emergence of new MDR strains, adverse effects of the 'newly' recommended antibiotics, and re-emergence of infections that previously were uncommon. Whilst many of these consequences such as resistance will take years to manifest, other potentially harmful effects may be more overt over a shorter term. These include antibiotic-related toxicity, such as aminoglycosideinduced nephrotoxicity or ototoxicity, or the concern that 'older' narrower-spectrum agents used in combination may be less clinically effective leading to increased mortality, greater re-admission or higher rate of complications. There is evidence of increasing use of agents such as co-trimoxazole, tetracyclines, fosfomycin and temocillin, amongst others, as part of treatment regimens to replace the broader spectrum CDAs. Therefore, for any range of improvement measures we need to collect data on these balancing measures. Systems are presently being developed nationally and locally in collaboration with all NHS boards and professional communities [e.g. ear, nose and throat (ENT) and renal specialty groups] and will become an integrated part of the national surveillance programme. Reassuringly, early data from one Scottish board

Discussion

The SAPG work plan has not been designed to reflect a robust scientific evaluation of the impact of a national antimicrobial stewardship programme. We have adopted a pragmatic 'real-world' approach to antimicrobial stewardship that has combined components of project management, quality improvement, information management and performance assessment through accountability or judgement measures. These are co-ordinated nationally but implemented locally by AMTs that work closely with IPCTs and others, all of which are embedded within the patient safety collaboration.

The teams are supported by a powerful clinical network and are underpinned by a robust educational support that is dynamic to meet the needs of local healthcare professionals. Research opportunities have been limited and have focused around using rigorous scientific methodology, for example time series analysis with transfer function modelling [START_REF] Aldeyab | Quasiexperimental study of the effects of antibiotic use, gastric acid-suppressive agents, and infection control practices on the incidence of Clostridium difficile-A c c e p t e d M a n u s c r i p t associated diarrhea in hospitalized patients[END_REF][START_REF] Vernaz | Temporal effects of antibiotic use and Clostridium difficile infections[END_REF], to evaluate the local and national benefit and any adverse impact of our interventions. SAPG at its inception had a range of objectives, but the initial focus was to support infection control measures to achieve the Scottish Government's CDI HEAT target for 30% reduction of CDI by March 2011. The use of prescribing indicators as national targets to support this overarching goal appears to have been successful. However, there are clearly inherent difficulties where measures for accountability or A c c e p t e d M a n u s c r i p t judgement are used to promote quality improvement. For example, Chassin et al. [START_REF] Chassin | Accountability measures-using measurement to promote quality improvement[END_REF] argue that recent accountability measures in US hospitals promote quality improvement. However, measurement for the purpose of accountability or judgement and measurement for the purpose of improvement of healthcare processes are two very different things [START_REF] Solberg | The three faces of performance measurement: improvement, accountability, and research[END_REF]. The two approaches can play complementary roles in advancing organisational goals if properly understood, but confusing measurement for accountability with measurement for improvement can give rise to organisational confusion [START_REF] Perla | Accountability measures to promote quality improvement[END_REF]. The reasons for this are two-fold: (i) measurement does not equate with improvement, which requires making changes to healthcare processes and structures; and (ii) measurement for improvement is not focused on judging whether data meet a compliance threshold or target but rather is a means of determining whether the changes we make to improve are effective and to what degree. Furthermore, quality improvement incorporates sets of related measures (process, outcome and balancing) to help us understand the broader effect of the changes tested [START_REF] Indicator | An approach to the evaluation of quality indicators of the outcome of care in hospitalized patients, with a focus on nosocomial infection indicators[END_REF]. The most effective strategy to implement these interventions is a key to their success. Feedback reporting of data combined with an implementation strategy, which includes educational support, has proved to be most consistently effective [START_REF] De Vos | Using quality indicators to improve hospital care: a review of the literature[END_REF]. We believe that SAPG, which has adopted such an approach, as well as our collaborative working with local AMTs has achieved a high degree of success at Effective antimicrobial stewardship will significantly contribute to the HAI agenda and will preserve or increase the longevity of the effectiveness of antibiotics [START_REF] Gaynes | Preserving the effectiveness of antibiotics[END_REF].

However, when considering future metrics and targets for HAI and antibiotic use, decision-makers must make a careful and balanced choice based on the available scientific evidence to support their use as well as local priorities. It is unlikely that even complete compliance with all the proposed measures will reduce the risk of HAI to zero [START_REF] Carlet | The 'zero risk' concept for hospital acquired infections: a risky business![END_REF] and this realism should be reflected in any future metrics or targets [START_REF] Brown | Never events': not every hospitalacquired infection is preventable[END_REF]. National antimicrobial prescribing indicators introduced by the Scottish Government in 2009

M a n u s c r i p t

• Hospital-based empirical prescribing: antibiotic prescriptions are compliant with the local antimicrobial policy and the rationale for treatment is recorded in the clinical case note in ≥95% of sampled cases.

• Surgical antibiotic prophylaxis: duration of surgical antibiotic prophylaxis is <24 h and compliant with local antimicrobial prescribing policy in ≥95% of sampled cases.

•

A

  c c e p t e d M a n u s c r i p t community-based care to all inhabitants via services mainly supplied by public providers. There are an estimated 11 456 acute hospital beds in Scotland.

A

  c c e p t e d M a n u s c r i p t (19.2%) and glycopeptides (18.6%). Although regional differences were seen, this snapshot survey provided an early indication of high levels of use of broad-spectrum parenteral antibiotics, and a significant proportion of these prescriptions were deemed inappropriate. The emergence of the Clostridium difficile infection (CDI) epidemic in Scottish healthcare facilities suggested a link between such prescribing practice and CDI. The outbreak of CDI in the Vale of Level Hospital, NHS Greater Glasgow and Clyde, with a high number of deaths, brought this problem to the forefront of the public, politicians' and the national media's attention. (http://www.documents.hps.scot.nhs.uk/hai/sshaip/publications/cdad/cdad-review-2008-07.pdf). The need to implement a national antimicrobial stewardship programme in all healthcare settings to support existing infection control and environmental decontamination measures was accepted as a priority in a bid to contain and reduce CDI. The aim of SAPG, working with NHS boards and other stakeholders, is to implement a range of antimicrobial stewardship interventions intended to enhance the quality of antimicrobial prescribing to reduce unnecessary antibiotic use:  promote use of narrow-spectrum agents and reduce use of broad-spectrum antibiotics;  drive improvement in the quality of antibiotic use to improve clinical outcomes; and  minimise harm from antibiotics (mortality, CDI, resistance, adverse reactions).

A

  c c e p t e d M a n u s c r i p t Within NHS boards these interventions are delivered by local Antimicrobial Management Teams (AMTs). The aim of this review is to describe the SAPG programme and to summarise some results of the first 2 years of SAPG.

Fig. 1 )

 1 Fig. 1) by NHS National Services Scotland (NSS) [which comprises Health

A

  c c e p t e d M a n u s c r i p t SAPG also has close links with another part of NHS QIS, the Healthcare Environment Inspectorate (HEI) (http://www.nhshealthquality.org/nhsqis/6710.140.1366.html) process. This independent and external inspectorate was established in April 2009 by the Scottish Government to give NHS boards a proactive, assertive way to self-assess and report evidence, create a methodology for analysing NHS board evidence, risk assess and identify targets for inspection, carry out and report on hospital inspection findings in the public domain, continuously monitor NHS board improvement plans, and make recommendations to Scottish ministers. SAPG influenced the design and content of the stewardship component of the Inspectorate's online self-assessment, which was based on the Infection Control Standards. SAPG membership consists of key disciplines, including antimicrobial pharmacists, microbiologists, information and antimicrobial surveillance scientists, infectious diseases specialists, hospital medical and non-medical leadership, infection prevention specialists, a public partner representative, dentistry, veterinary medicine, quality improvement, primary care clinicians and the pharmaceutical industry. Other expert advisers are invited to contribute to specific projects on an ad hoc basis. SAPG meets every 2 months and a Project Board has been set up to provide clinical and financial governance. During its first 3-year work plan, SAPG has developed five workstreams to take forward various aspects of ScotMARAP and each has a work plan with defined timescales. A website has been in place since 2008 (http://www.scottishmedicines.org.uk/SAPG/Scottish_Antimicrobial_Prescribing_Gro up__SAPG_; accessed 25 February 2011) and provides access to a range of

A

  c c e p t e d M a n u s c r i p t material from membership and meeting minutes to updates of national policy and guidance, details of national events, reports on progress with the different workstreams described in this review, and links to other work on patient safety and HAI.

A

  c c e p t e d M a n u s c r i p t availability of antimicrobial pharmacists within each NHS board, recognising the pivotal role of the antimicrobial pharmacist within the AMT [11]. The remit of the AMT and antimicrobial pharmacist is to support stewardship in primary and secondary care. AMTs work closely with local Infection Prevention and Control Teams (IPCTs), attending clinical teams and also local clinical governance and patient safety teams to ensure local delivery of antimicrobial stewardship and HAI prevention. To foster more efficient working across all teams, there is a clear move to improve the strategic and operational alignment of goals and responsibilities under the overarching umbrella of patient safety with delivery through the improvement framework.

  SAPG has also been able to integrate antimicrobial stewardship into the wider HAI agenda at board level primarily via the HEI process described earlier. In relation to stewardship, the results of inspections in acute hospitals have been generally favourable, which has confirmed good progress with the implementation of key

A

  c c e p t e d M a n u s c r i p t structures and leadership within organisations as well as a good level of implementation of SAPG guidance, policies and educational initiatives. The HEI noted that antimicrobial management has been raised as a high priority for NHS boards, and local AMTs have been established in all NHS boards to lead antimicrobial management programmes. Future alignment of all local HAI stakeholders around a unified patient safety and quality improvement agenda will be assessed through this and other routes.

A

  c c e p t e d M a n u s c r i p t issued in July 2008 and this was followed up with 'Hospital antibiotic management: minimum requirements for antimicrobial prescribing policies' in December 2008 and 'Antibiotic prophylaxis in surgery' in July 2009

  prophylaxis. This guidance was developed in collaboration with local pharmacokinetics experts and taking into account local and national antibiotic susceptibility data for the relevant pathogens. Successful and widespread local adoption and implementation, A c c e p t e d M a n u s c r i p t albeit over different time frames, has been reported via our regular surveys to AMTs and confirmed via the HEI process.

  The DDD is the internationally recognised technical unit of measurement of medicine consumption recommended by the World Health Organization (WHO) as the standard to allow comparative use of medicines over time and between different locations. The DDD is the assumed average maintenance dose per day for a medicine used in its main indication in adults. In general, the DDDs for antibacterials are based on their use in moderately severe infections, but for antibacterials only used in severe infections their DDDs are assigned accordingly. For further details on DDD methodology please see the WHO Collaborating Centre for Drug Statistics Methodology website (http://www.whocc.no/atcddd/). A major achievement in 2008-2009 was the development of a set of 41 nationally agreed prescribing indicators on primary care use of antibacterials as standard reports within the web-based Prescribing Information System for Scotland (PRISMS). Prescribing indicators are objective measurements that are used to monitor use of antibacterials over time, between geographical areas and against A c c e p t e d M a n u s c r i p t national averages. These indicators are intended to support AMTs and primary care teams by providing a complete picture of the use of antibacterials and to identify areas for improvement in prescribing practice. A report showing the key indicators focusing on the initial SAPG priority areas is available at http://www.isdscotland.org/isd/6125.html (accessed 20 January 2011). One such indicator is the overall number of antibacterial prescriptions. In 2009 the overall use of systemic antibacterials, expressed as number of items per 1000 population per day (items/1000/day), was 1.6% lower than in 2008 and is equivalent to 44 500 fewer prescriptions in 2009 than in 2008. This is the first annual reduction since 2004 but it remains to be seen whether this small reduction is the start of a trend. In 2009 our data also show that progress has been made toward restricting use of CDAs; specifically, the use of penicillin combinations (co-amoxiclav) in 2009 was 14.7% lower than in 2008 (expressed as items/1000/day), which is the largest annual reduction since 1999. Use of fluoroquinolones in 2009 was 7.1% lower than in 2008, the first annual reduction since 2002 and there was also a 21.2% reduction in the use of cephalosporins in 2009 compared with 2008. The use of first-line antibacterials promoted in SAPG's Management of Infection Guidance for Primary

A

  c c e p t e d M a n u s c r i p t Scottish hospitals in previous European Surveillance of Antimicrobial Consumption (ESAC) surveys [24]. Data on Scottish national standardised quantitative and qualitative information on antibacterial use in hospitals were not available, so to establish a national baseline of the prescribing landscape in hospitals SAPG coordinated national participation in the 2009 ESAC point-prevalence survey (PPS). ESAC PPS generally has participation from one or two hospitals from each country but, through promotion to AMTs and securing the support of senior NHS managers and clinicians, 31 Scottish hospitals participated and reviewed 8732 patients during May and June 2009. SAPG also provided support for data entry where this was not possible by AMTs. A comprehensive national report comparing the results in Scotland with European data was produced and was disseminated to all NHS boards to enable participating hospitals to benchmark local results against the national findings. The report is available at http://www.scottishmedicines.org.uk/files/ESAC_report_final_060510.pdf.

  major increases in resistance (to the antibiotics tested) were observed among the key Gram-negative organisms (E. coli, K. pneumoniae and P. aeruginosa) when comparing 2009 with 2008. In contrast, resistance to third-generation cephalosporins in E. coli decreased significantly in this period. Stabilisation of resistance A c c e p t e d M a n u s c r i p t development seen in Scotland in 2009 is unusual. In the 10-year period in which resistance in Gram-negatives has been monitored throughout hospitals in Europe, resistance trends have mostly been going up. It is interesting to speculate whether the effective restriction of cephalosporins in Scotland could be associated with the containment/decrease in resistance. One exception to the general downward/stable trend was a minor increase in resistance to aminoglycosides in E. coli, which rose from 7.3% in 2008 to 8.2% in 2009 (a non-significant change, P > 0.05). Resistance

  . The European Centre for Disease Prevention and Control (ECDC) have in 2010 A c c e p t e d M a n u s c r i p t recognised carbapenemase-producing Enterobacteriaceae as a significant risk for public health in Europe and worldwide as treatment options for these infections are very limited. Resistance among Gram-positive isolates remain less of a concern overall in Scotland and there were few changes in resistance proportions from 2008 to 2009. With the exception of meticillin-resistant S. aureus (MRSA), resistance remains low in the Gram-positives. One exception to this is the increase in resistance of E. faecium to vancomycin. Resistance has increased from 17% in 2008

  This work, led by NHS NES, involves scoping and development of training materials on antimicrobial stewardship both for undergraduate and postgraduate healthcare professionals. A range of online resources are available on the website http://www.nes.scot.nhs.uk/initiatives/healthcare-associated-infection/online-shortcourses (accessed 7 December 2010). A framework of learning outcomes for antimicrobial stewardship that aligns with 'The Scottish Doctor' has been developed after broad consultation, and SAPG has recommended its adoption into the curricula of the five Scottish Medical Schools and A c c e p t e d M a n u s c r i p t we plan to assess progress with its implementation in 2011. The framework is also being evaluated by the two Schools of Pharmacy in Scotland to ensure that those learning outcomes applicable to pharmacists are covered by their undergraduate curricula. The Doctors Online Training System (DOTS), a mandatory web-based education resource for all foundation training doctors in Scotland, has been revised to highlight current issues and the August 2009 cohort of doctors was the first to undertake the revised programme. Access to the DOTS programme has recently been extended to allow other medical staff, pharmacists and non-medical prescribers to undertake the training, and a primary care module has also been added. An evaluation of DOTS carried out by NES in 2007 revealed a high level of participation and satisfaction among Scottish foundation doctors (http://www.nes.scot.nhs.uk/media/813342/nes%20fy%20antimicrobial%20training% 202008.pdf; accessed 7 December 2010).

A

  c c e p t e d M a n u s c r i p t Training for pharmacists on the pharmaceutical care of patients with infections has been developed and delivered throughout Scotland to over 900 community and hospital pharmacists. To address variation between NHS boards in training provision on antimicrobial stewardship for junior doctors and other new clinical staff, an induction pack has been produced and made available for AMTs and other staff involved in training. This piece of work has been commended by the HEI (http://www.nes.scot.nhs.uk/initiatives/healthcare-associated-infection/trainingresources/training-on-the-use-of-antimicrobials-in-clinical-practice; accessed 7 December 2010).

  9] in April 2009 announced a CDI HEAT (Health Efficiency and Access to Treatment) target defined as a reduction in the rate of CDI among people aged ≥65 years by at least 30% by 31 March 2011 (this was increased to 50% in May 2010) [27]. The Scottish Government and SAPG A c c e p t e d M a n u s c r i p t agreed three supporting antimicrobial prescribing indicators to underpin this HEAT target and these are summarised in Table

A

  c c e p t e d M a n u s c r i p t Government's target of ≤5% seasonal variation in fluoroquinolone use and that for the first time in 2009 the target has been met at a national level. This may reflect the impact of initiatives led by AMTs and primary care teams to reduce inappropriate use of fluoroquinolones since the introduction of target. The negative seasonal variation seen in some boards means there was a lower use of fluoroquinolones in the winter of 2009 than in the previous summer, but this effect is expected to disappear in subsequent years as overall fluoroquinolone use reduces.

  these national interventions separately from other infection control measures. Local data from one region (NHS Tayside) suggest a strong link between the A c c e p t e d M a n u s c r i p t implementation of restrictive measures and local reduction in CDI (N. Vernaz et al., pers. comm.).

A

  c c e p t e d M a n u s c r i p t suggest that following introduction of a restricted empirical policy for managing sepsis there was no related increase in mortality in an Acute Medical Admissions Unit (B. White et al., NHS Lanarkshire, pers. comm.). Similar data are being collected and analysed from other hospitals throughout Scotland.

  national and local levels. The HEAT target and associated prescribing indicators have clearly resulted in engagement from hospital leadership, clinicians have accepted their need, at least for the medium term, and have provided SAPG with a focus to measure its interventions. However, the development of the pneumonia care bundle measures and close collaboration with the SPSP in the area of surgical prophylaxis demonstrates SAPG's long-term desire to embrace the improvement

A

  c c e p t e d M a n u s c r i p t approach to improving antibiotic use. National collaboration to develop and implement a national antibiotic change package that would encompass an antibiotic review bundle, for continuing care, is another example of our direction of travel. From 2011 to 2014 SAPG plans to undertake the following actions, which are aligned with the HAI Taskforce Delivery Plan 2011-14 and will support NHS boards and frontline clinical staff to enhance the quality of antimicrobial prescribing to deliver safe, effective, patient-centred care. These include: (i) integration of core SAPG work with key local, national and international stakeholders working in HAI, and quality improvement both at strategic and operational levels; (ii) maintaining delivery of existing stewardship activities and evaluation of their impact at local and national levels; (iii) development of antimicrobial stewardship activities in primary care integrated with other national programmes; (iv) application of quality improvement methodology to clinical priority areas to optimise patient care in the management of infections; and (v) development and promotion of an evidence base for antimicrobial stewardship interventions and antimicrobial resistance.

Fig. 1 .

 1 Fig. 1. Key national and local stakeholders.

Fig. 2 .

 2 Fig. 2. Empirical prescribing indicators, national data.

Fig. 3 .

 3 Fig. 3. National Health Service (NHS) Scotland percent seasonal variation in

Fig. 4 .

 4 Fig. 4. Overall quarterly Clostridium difficile infection rates for Scotland [per 1000

Table 1 National

 1 Health Service (NHS) Scotland percent change in key primary care prescribing indicatorsClostridium difficile infection; SAPG, Scottish Antimicrobial Prescribing Group; DDD, defined daily doses. a Number of items or DDD per 1000 population per day.

A c c e p t e d M a n u s c r i p t Table 3

 3

  Antibiotics compliant with empirical prescribing policyBy September 2010, one NHS board achieved the target of ≥95% compliance with the measure antibiotics compliant with empirical prescribing policy. Median compliance ranges from 65% to 89%.Indication for antibiotic treatment recorded in notesBy September 2010, eight NHS boards were achieving the target of ≥95% compliance with the measure indication for antibiotic treatment documented in the notes. Median compliance ranges from 87% to 97%.

  Primary care empirical prescribing: seasonal variation in quinolone use (winter months versus summer months) is ≤5%, calculated from PRISMS data held by NHS boards. PRISMS, Prescribing Information System for Scotland.

Acknowledgments

The authors wish to acknowledge the support of the Scottish Medicines Consortium (SMC), all members of the Scottish Antimicrobial Prescribing Group (SAPG) Steering Group, all Antimicrobial Management Teams (AMTs) and the clinicians who have supported the work of SAPG. Special thanks to their collaborators, Nathalie Vernaz and Stephan Harbarth, from Hôpitaux Universitaires de Genève (Switzerland).

This programme, led by SAPG, is delivered by NHS National Services Scotland (

Funding

The Scottish Antimicrobial Stewardship Programme is supported by funding from the Scottish Government Health Department.

A c c e p t e d M a n u s c r i p t

In conclusion, we hope that in the future we will not only be able to provide an update regarding our progress in achieving these goals but share our experience and learning with the stewardship community. We also hope that the publication of this report will not only fulfil one of our objectives of sharing our experiences and work with the international community but encourage collaborations by fostering links with other national programmes. Our journey has just begun, we are encouraged by our early efforts and success but we have much to do and learn from each other.

Competing interests

None declared.

Ethical approval

Not required.

Local data for NHS Tayside (as an example board)

This includes data from September 2009 to September 2010. The median compliance for NHS Tayside for each of the three measures is:

 antibiotics compliant with empiric policy: 83%

 indication documented in patient's notes: 86%.

 combined measure, antibiotics compliant and indication documented: 82%.

Action: To facilitate improvement, areas of non-compliance should be identified and discussed with front-line staff.

Note: By September 2010, one board achieved ≥95% compliance with the measure antibiotics compliant with empirical prescribing policy, eight boards achieved ≥95% compliance with the measure indication for antibiotic treatment documented in notes, and no board achieved ≥95% compliance with the combined measure.


Inga Gheorghita
email: inga.gheorghita@atilf.fr

Jean-Marie Pierrel
email: jean-marie.pierrel@atilf.fr

Towards a methodology for automatic identification of hypernyms in the definitions of large-scale dictionary

Keywords: hypernymy, dictionary, thesaurus

The purpose of this paper is to identify automatically hypernyms for dictionary entries by exploring their definitions. In order to do this, we propose a weighting methodology that lets us assign to each lexeme a weight in a definition. This fact allows us to predict that lexemes with the highest weight are the closest hypernyms of the defined lexeme in the dictionary. The extracted semantic relation "is-a" is used for the automatic construction of a thesaurus for image indexing and retrieval. We conclude the paper by showing some experimental results to validate our method and by presenting our methodology of automatic thesaurus construction.

Introduction

Linguistic resources such as dictionaries, computational lexicons, semantic taxonomies and thesauri are an important source of knowledge for natural language processing applications. The information contained in linguistic resources, depending on their type, includes semantic relations (eg. thrush is a kind of bird), text definitions (eg. the Oxford dictionary defines the "lion" as "a large tawny-colored cat that lives in prides"), examples on the usage domain, and so on. Unfortunately, not all of which provide structured information that can be used by applications of natural language processing (Harabagiu, Miller, & Moldovan, 1999). A human understands the meaning of a word just by reading its definition in the dictionary, but it's not the case for a computer system. The main cause is that the semantic information, such as definitions, contained in the lexical resources is not very explicit and is provided in the form of free text. Even WordNet (Miller, 1995), one of the most popular lexicons for the English language, uses definitions to explain the meaning of ambiguous words. However, compared with other electronic dictionaries and thesauri, which represent only an electronic transcription of their paper version, WordNet contains explicit information in the form of semantic relations such as, meronymy and hypernymy. Over the last several decades much research has been done on the automatic construction of resources from corpora (Hearst, 1992), (Yarowsky, 1992), in particular by creating hypernym hierarchies. Various techniques as Machine Learning (Snow, Jurafsky, & Ng, 2005), Hidden Markov Model (Ritter & Soderland, 2009) and resources as dictionaries (Nakamura & Nagao, 1988) and thesauri (Kennedy & Szpakowicz, 2007) are used for identification of hypernymy or other semantic relations in the text. In this paper, we aim to make explicit the information that is implicitly contained in the definitions of "Trésor de la Langue Française informatisé" 1 (TLFi) (Dendien & 1 Treasury of the French Language Computerized Pierrel, 2003). We are interested in determining from a definition of TLFi the hypernymy relation that will be used for automatic construction of a thesaurus for image indexing and retrieval (Gheorghita, 2011). More precisely, we determine the possible hypernyms for a particular dictionary entry by exploring its definitions. In order to do this, we propose a weighting methodology that lets us assign to each lexeme the weight it has in a definition. This fact allows us to predict that the lexemes with the highest weight are the closest hypernyms of the defined lexeme in the dictionary.

Hypernymy in lexical models

Hypernymy is a lexical function that for a term t associates one or more other general terms. Logical definitions (or Aristotelian) are generally composed of a "genus" and "differentiae". In most of the definitions of this type, the hypernymy is represented by the relation "is-a". A is a hypernym of B if B is an A (a kind / type / kind of A) and if A is a classifier of B. This means that concept B is a specialization concept of A, and concept A is a generalization concept of B. For example, « mammal » is a generalization of « lion, wolf». In linguistic resources like thesauri, WordNet, lexical entries are linked to other lexical entries by semantic relationships, so in WordNet the entry for big would somehow represent that its antonym is small. In this type of lexical model the relations that a word has to others partly determine the word's sense. In dictionaries, the meaning of lexemes is divided into several parts (Murphy, 2010). The information necessary for determining the semantic relations among words in dictionaries is contained in theirs definitions. Thus, we can determine the semantic relations between lexemes by a set of rules such as "A is the hyponym of B iff it has the same components as B, plus at least one more". Compared to WordNet, the TLFi defines the meaning of a word only by a definition. The single information that can disambiguate the meaning of an input of TLFi is the domain 2 of definition. But only 31% of definitions have a domain. The definitions without a domain are assigned to the "generic" domain. It means that the sense of the word is also valid in the other domains. The majority of definitions of TLFi for nominal entries are logical where usually the first word of the definition is the hypernym of the entry. In the TLFi the semantic relations are not explicit. To determine the possible hypernyms of a TLFi entry, we calculate the weight of each noun in the definitions for a given domain. We assume that the nouns with the highest weight are the best hypernyms of the TLFi entry.

The word weighting method in the dictionary definitions

Our approach based on the analysis of the structure, the size and the meta-language of dictionary definitions, has allowed us to define a weighting method, which estimates the importance of lexemes in a definition. Thus, to calculate the final weight of the lexeme, we take into account the importance of the lexeme in a definition (local weighting), the of the lexeme in the collection of definitions for a given domain (overall weight) and the position of the lexeme in the chain of characters of the definition.

The importance increases proportionally to the number of times a word appears in the definition, and to the number of times a word appears in the collection of definitions for the given domain but is offset by the position in the definition.

The weight of a term t in a definition d for the domain D is defined as follows:

! !! !"#$ !, ! !"#$ ! ! , ! ! * ! ! ! , ! ! !, ! * log ! ! !"# ! !"# !, !ℎ where: !"#$ !, ! : frequency of a term t in the definition d !"#$ ! ! , ! ∶ !
frequency of all terms ! ! in the definition d ! ! ! , ! : number of definitions in the collection for the domain D that contain the term t ! !, ! ∶ number of definitions in the collection for the domain D ! !"# : number of positions in the string of a definition d ! !"# !, !ℎ : number of position of term t in the string ch of a definition d The position of the lexeme is a very important indicator since the definitions of the dictionary are written by lexicographers according to some rules and using a specific meta-language. In the definitions, the meta-language terms occurred very often. Their weight is quite high compared with the weight of the other lexemes. It is for this reason that we created the specific classes for each type of meta-language terms. This fact allows us to distinguish the meta-language term from the lexeme and to increase or decrease the weight of the lexeme in dependence of its position with the meta-language term. Contrary to other weighting formulas as TF.IDF (Spark Jones, 1972) which favor the discriminants and rarest terms, our goal is to give more weight to the lexemes located at the beginning of the definition, considered as class representatives, and to the discriminant terms in the collection of definitions for a given domain, considered as specific characteristics. According to the hypothesis made before, that the term with the higher weight is considered to be a best hypernym for the input e of TLFi, the weighting method is used to determine the list of possible hypernyms for the given term e. Jointly used with the inclusion model, which defines a set of rules of inheritance of properties from one class by a subclass, we build a thesaurus as a hierarchical tree where the terms are related by the relation "is-a".

Evaluation of results and discussion

We applied our approach to 132 743 definitions that correspond to 51 778 nominal entries in a dictionary. Table 1 shows examples of possible hypernyms for dictionary entries ranked by their weight in the definition. We noticed that the lexeme with the highest weight is not always the best hypernym of the dictionary entry. It is usually a meta-language term like family of, form of or a lexeme very characteristic of a given domain like system for medical domain and tribunal for law domain. This fact is explained by their high frequency in the collection of definitions for the given domain. However, the lexeme that can be considered as the best hypernym, like fruit for avocado, is in the list of the first three possible hypernyms. To determine it precisely, the frequent terms must be filtered and eliminated from the list of possible hypernyms.

We evaluated the quality of our methodology, by using the structured definitions of TLFi within the Definiens project (Barque, Nasr, & Polguère, 2010). In these definitions, the semantic markers are a central component (CC) and peripheral components (CP), which have been annotated manually. We assumed that the lexemes, with the highest weight in the list of possible hypernyms, must be located in the central component of the structured definitions. To prove our hypothesis, we calculated the precision. The precision of our results is the proportion of lexemes with the highest weight in the definitions determined as the central components in the structured definitions of Definiens project. Since the Definiens project has not been finished yet, we could only test our hypothesis for 15 000 dictionary entries. Figure 1 shows the precision for the first three lexemes of maximum weight. 1: Example of possible hypernyms ranked by their weight in the definitions of dictionary entries For the first three possible hypernyms, we obtained a high precision that decreases with the rank of the hypernym. It proves that the first lexemes with the highest weight represent the best possible hypernyms for a dictionary entry. These experiments demonstrate that our weighting methodology estimates correctly the importance of lexeme in a definition and allows us to determine with a best precision the first three possible hypernyms for the defined lexeme.

Exploitation of results

Extracted semantic relations from dictionary definitions are usually used to enrich existing taxonomies (Navigli & Velardi, 2008). Our aim is to use the hypernymy relations obtained from dictionary to construct a hierarchy of type "is-a". In this section we present the algorithm of automatic construction of thesaurus, which is based on our methodology of hypernyms identification. The idea of the algorithm is to create a thesaurus from the words by using their definitions of TLFi. The algorithm is based on two processes. The first process aims to transform words into the thesaurus nodes. The second process allows those nodes created from the first process to be hierarchized.

Creation of nodes of the thesaurus

The objective of this process is the transformation of words in the thesaurus nodes. This process involves two steps: a) Extracting data from the TLFi for a given word X. For each given word X we get from the TLFi a list of data composed of the domains of its definitions, lexemes with their weights and positions in the definitions of each domain.

b) Transformation of the data list of a given word X

in nodes of the thesaurus. From the data extracted for a given word X we proceed to the creation of nodes of thesaurus. A node is a data structure. We distinguish 3 types of nodes: domain node, word node and lexeme node. Depending on the type of node, the data structure is different. For the domain node the data structure is limited to the domain name and its identifier. The structure of the word node consists only of word and that of the lexeme node contains the word, the lexeme, its weight, its position, the identifier of the definition, the domain and its identifier. Thus, we consider as the nodes of the thesaurus each word X as well as its domains and extracted lexemes.

Construction of hierarchy of nodes

The goal of this process is to organize in a hierarchy the created nodes. The hierarchical tree is built by comparing the data structures of each node with the other. This process is realized in several steps: a) Determination of parent nodes for a given word X node. Using the created nodes, we determine the parent nodes of word X node. To do this, we group the lexeme nodes by their definition identifier and for each created group we determine the node whose weight is maximum. This node becomes the parent node for word X node. Thus, several different parent nodes (as much as different definitions of the word in the TLFi) are created having as child node the word X node. Then the following steps are executed: If in a group there are two nodes of the same maximum weight, but having different lexemes then the two nodes become different parent nodes for word X node. If for two groups, emerge two nodes of the same maximum weight having the same domain and lexeme then if these nodes have the same position then only one node becomes the parent node of the word X node; else we determine for each group the second node whose weight is maximum and these nodes become parent nodes of word X node.

b) Determination of child nodes for the created parent nodes.

In order to determine the child nodes of the created parent nodes, we proceed to the creation of the other nodes. New nodes are created from existing lexemes nodes. This procedure consists of executing the first process (5.1) for each lexeme node. The structures of new obtained nodes (named lexeme nodes II) are compared with the created parent nodes by identifying the lexeme nodes II, which have the same lexeme as the created parent nodes. If such nodes are found, we check:

if their position is minimal (1-3) and they have the same domain as the parent nodes or generic domain then these lexeme nodes are replaced by words nodes corresponding to words of lexemes nodes and they become the child nodes of the created parent node.

c) Transformation of child nodes in the parent nodes of word X node.

In order to allow the growth of thesaurus in depth we determine for word X node the new parent nodes. Thus, we compare the child nodes with lexemes nodes II. If the existing lexeme nodes II have the same lexeme as the word of the word X node and the same word as the child node, we check: if their position is minimal (1-3) and they have the same domain as the word X node or generic domain then these nodes become parent nodes of word X node.

d) Determination of the hierarchy for domain nodes.

For each domain node, we determine its parent node by exploiting the thesaurus3 of the TLFi's domains. Thus, we compare domain nodes with parent nodes determined during the step one of the second process. If these nodes have the same domain, then the domain nodes become parent nodes for these.

e) Assignment of associative nodes to the word X node. The constructed thesaurus will be used for indexing and search of images. Thus, the associative nodes are the nodes that during the search of images will be used to direct the user to nodes situated at the bottom of the hierarchy. Associative nodes are nodes that have not been used for the creation of the thesaurus and, compared to other nodes of the thesaurus, they are not used for indexing. The assignment of these associative nodes corresponds to the following process: If the domains and the definitions' identifiers of lexeme nodes not used for the creation of the thesaurus are identical to those of the parent node of the word X node then these nodes are assigned to the word X node.

Conclusion

In this paper, we have proposed a new methodology to calculate the weight of lexemes in dictionary definitions.

We have showed that our method allows us to determine precisely the possible hypernyms for the defined lexeme.

The first evaluation of our method has given the best precision of 72,35% for the first hypernyms, which weight is the highest in the definition. The utility of our approach is that it can be used to determine the hypernymy relation in the machine-readable dictionaries where usually the semantics relations are not explicit. Thus, based on determined hypernymy relation we have presented our algorithm of automatic construction of thesaurus using dictionary definitions. The constructed thesaurus will allow the disambiguation of the sense of words by improving the precision of the image search. For example, the system will be able to provide for the query "ananas" 3 types of images corresponding to 3 senses (plant, fruit, color) of the lexeme ananas in the TLFi. Currently, we are working on the implementation of the algorithm of automatic construction of thesaurus. This fact will allow a second evaluation of our methodology for automatic identification of hypernyms in the

Figure 1 :

 1 Figure 1: Precision for the first three lexemes

This resource was created by normalizing the domains of dictionary and using the documentation on the thesaurus of techniques of TLFi, that contains all domains and subdomains used during the writing of TLFi's definitions.

definitions of dictionary. We also plan to compare the extracted hypernyms with those already available in the existing thesauri or computational lexicons. With the addition of some improvements such as the filtration of meta-language terms, we believe that this automatic method of identifying hypernyms will allow us to construct a truly hierarchical tree of type "is-a".

Barque, L., Nasr, A., & Polguère, A. (2010) (1972). A statistical interpretation of term specificity and its application in retrieval. Journal of Documentation,28(1),