Annual Report Scottish One Health Antimicrobial use and Antimicrobial Resistance.

Transcription

1 Annual Report Scottish One Health Antimicrobial use and Antimicrobial Resistance.

2 Health Protection Scotland is a division of NHS National Services Scotland. Health Protection Scotland website: Published by Health Protection Scotland, NHS National Services Scotland, Meridian Court, 5 Cadogan Street, Glasgow G2 6QE. First published November 2017 Health Protection Scotland 2017 Acknowledgements Health Protection Scotland (HPS) and Information Services Division (ISD) would like to thank the following for all their assistance in producing this report: NHS diagnostic laboratories within Scotland, Scottish Haemophilus, Legionella, Meningococcus and Pneumococcus Reference Laboratory (SHLMPRL), Scottish Meticillin Resistant Staphyloccus aureus Reference Laboratory (SMRSARL), Scottish Salmonella, Shigella and Clostridium difficile Reference Laboratory (SSSCDRL), Scottish Bacterial Sexually Transmitted Infections Reference Laboratory (SBSTIRL), Antimicrobial Resistance and Healthcare Associated Infections (AMRHAI) Reference Unit at Public Health England (PHE), Scottish Antimicrobial Prescribing Group (SAPG), Scottish Microbiology and Virology Network (SMVN), Scotland s Rural College (SRUC) which includes Scottish Agricultural College (SAC) Veterinary Services and Capital Diagnostics in Scotland, Scottish Environmental AMR Group (SEAG), Food Standards Scotland (FSS). Reference this document as: Health Protection Scotland. Scottish One Health Antimicrobial Use and Antimicrobial Resistance Report Health Protection Scotland, 2017 [Report] Health Protection Scotland has made every effort to trace holders of copyright in original material and to seek permission for its use in this document. Should copyrighted material have been inadvertently used without appropriate attribution or permission, the copyright holders are asked to contact Health Protection Scotland so that suitable acknowledgement can be made at the first opportunity. Health Protection Scotland consents to the photocopying of this document for professional use. All other proposals for reproduction of large extracts should be addressed to: Health Protection Scotland NHS National Services Scotland Meridian Court 5 Cadogan Street Glasgow G2 6QE Tel: +44 (0) NSS.HPSEnquiries@nhs.net

3 Table of contents Executive Summary List of abbreviations and acronyms Introduction 1 Human Antimicrobial Use 4 Antibiotic use in humans 4 Antibiotic use in primary care 6 Antibiotic use in acute hospitals 10 Antibiotic use in dentistry in primary care in Scotland 15 Antifungal use in humans 17 Antifungal Susceptibility 20 Antimicrobial Resistant Infections 22 Healthcare associated infections and AMR: Gram-negative bacteraemia 22 E. coli bacteraemia 23 Other Gram-negative bacteraemia 24 K. pneumoniae 24 K. oxytoca 25 P. aeruginosa 25 Acinetobacter spp. 25 Antimicrobial non-susceptibility in urinary isolates 26 Antimicrobial resistance among selected combinations of antibiotics used empirically to treat systemic and/or severe bacterial infections 27 Carbapenemase-producing organisms 28 Staphylococcus aureus bacteraemia 31 MRSA screening and mupirocin resistance 32 Enterococcal antimicrobial resistance 33 Gonococcal antimicrobial resistance 35 HIV antiviral resistance 37 Non-typhoid Salmonella 39 Human 40 Animal 40 Shigella 42 Antimicrobial Resistance in Animals 43 Antimicrobial resistance in veterinary clinical isolates 43 Selected organisms 44 Antimicrobial resistance in non-clinical, animal isolates 48 E. coli 48 Conclusion 48 References 49 ii v i

4 Executive Summary Antibiotics are life saving drugs, but unnecessary and inappropriate use reduces their ability to treat infections. Antibiotic use and spread of infection in humans, animals and the environment contribute to the development of resistant infections. A One Health approach, tackles antimicrobial resistance (AMR) and its drivers across all settings. This report describes a range of AMR and antimicrobial use (AMU) data in human, and for the first time, animal infections. TOTAL ANTIBIOTIC USE 79.8% of antibiotic use in humans occurred in primary care. Antibiotic use has reduced but more needs to be done ACUTE HOSPITALS Antibiotic use increased in , ,000 DDD/1000/Day DDD/1000ADM 5,500 5, , Year 4, Year Use the 4Ds approach to improve prescribing: duration, discontinue, de-escalate, diversify CARBAPENEM USE Use of carbapenems -antibiotics of last resort- reduced in DDD/1000ADM Year 11.8% lower than % lower than 2012 Preserve carbapenems and other antibiotics of last resort for when they are really needed. Number of isolates CARBAPENEMASE-PRODUCING ORGANISMS (CPOs) CPOs increased in Year Focus on carbapenamese producing enterobacteraceae (CPE) screening, CPO surveillance, use of acute and non-acute CPE toolkits, and referral of isolates to the Scottish AMR Satellite Reference Laboratory. ii

5 E. coli, the most common bacteraemias in recent years, remain high. Rates per population GRAM-NEGATIVE BACTERAEMIA The proportions of E. coli non-susceptible to some commonly used antibiotics also remain high. % Non-susceptible Year E. coli K. pneumoniae K. oxytoca P. aeruginosa Acinetobacter spp Year ciprofloxacin 3rd-generation cephalosporins gentamicin piperacillin/tazobactam co-amoxiclav carbapenems Focus on prevention and management of UTIs in hospitals and the community. The incidence of E. faecium bacteraemia has increased since VANCOMYCIN RESISTANT ENTEROCCAL BACTERAEMIA The proportion of E. faecium bacteraemia resistant to vancomycin is high and increasing. 40 Rates per population %Non-susceptible Year Year E. faecalis E. faecium Molecular sequencing to better understand the reasons for these increases is underway. The number of episodes of gonorrhoea per year has increased since Number of laboratory reports (episodes) Year Female Male Total GONOCOCCAL ANTIMICROBIAL RESISTANCE Similar to previous years, 42% of gonorrhoea infections tested were nonsusceptible to one or more commonly used antibiotics. No isolates with decreased susceptibility to ceftriaxone were observed, 4.9% of isolates tested demonstrated decreased susceptibility to azithromycin and there was a very small number of isolates which showed high level resistance to azithromycin in All isolates should be referred to the reference laboratory for resistance testing. iii

6 ANTIMICROBIAL RESISTANCE IN ANIMALS The report includes AMR in animal infections to help inform veterinary prescribing. Comparable human and animal Salmonella AMR data, which, although complex to interpret, represent the beginnings of One Health AMR intelligence in Scotland, are included. Further development of animal AMR and AMU surveillance systems is needed. SUMMARY In Scotland, in 2016, some improvements were evident in human AMU and AMR. However, there is still progress to be made, particularly in reducing: the burden of antibiotics in acute hospitals, Gram-negative bacteraemias, VRE bacteraemias, and CPO isolates. For AMR control focus on: detection and surveillance of resistant infections, infection prevention and control in the widest sense, and antibiotic stewardship. All clinical, care staff, health protection teams and veterinarians need awareness and understanding of AMR. The public has a part to play in keeping antibiotics working. To follow the advice of your healthcare professional (doctor, nurse, dentist or pharmacist) or vet for animals, regarding the need for antibiotics. iv

7 List of abbreviations and acronyms ADM Admissions AFR Antifungal Resistance AFS Antifungal Stewardship AMR Antimicrobial Resistance AMRHAI Antimicrobial Resistance and Healthcare Associated Infections AMTs Antimicrobial Management Teams AMU Antimicrobial Use ART Antiretroviral Therapy BASHH British Association for Sexual Health and HIV BBV Blood Borne Virus BHIVA British HIV Association BNF British National Formulary BSAC British Society for Antimicrobial Chemotherapy CARS Controlling Antimicrobial Resistance in Scotland CAUTI Catheter Associated Urinary Tract Infection CA-CDI Community associated Clostridium difficile Infection CDI Clostridium difficile Infection CFR Case Fatality Rate cfr chloramphenicol-florfenicol resistance CHI Community Health Index CLSI Clinical and Laboratory Standards Institute CPE Carbapenemase-producing Enterobacteriaceae CPO Carbapenemase-producing Organism CRA Clinical Risk Assessment DDD Defined Daily Doses ECDC European Centre for Disease Prevention and Control ESBL Extended-spectrum beta-lactamase EUCAST European Committee on Antimicrobial Susceptibility Testing FSS Food Standards Scotland GASS Gonococcal Antibiotic Surveillance in Scotland GES Guiana extended-spectrum GPs General Practitioners HAI Hospital Acquired Infection HCAI Healthcare Associated Infection HIV Human Immunodeficiency Virus HIVDRD UK HIV Drug Resistance Database HL-AziR High level azithromycin resistant HPS Health Protection Scotland IAS International Antiviral Society IBC Integron-borne cephalosporinase IMI Imipenem-hydrolysing beta-lactamase IMP Imipenem ISD Information Services Division ITU Intensive Therapy Unit ISO International Organization for Standardization KPC Klebsiella pneumoniae carbapenemase KPI Key Performance Indicator MBL Metallo-beta-lactamases MDR Multi-Drug Resistance MRSA meticillin resistant Staphylococcus aureus MSSA meticillin susceptible Staphylococcus aureus MSM Men who have sex with men v

8 NAAT Nucleic Acid Amplification Test NDM New-Delhi-metallo-beta-lactamases NES NHS Education Scotland NG-MAST Neisseria gonorrhoeae Multi-Antigen Sequence Typing NIM Nitroimidazole NMC Nursing and Midwifery Council NMC-A Non-metallocarbapenemase-A NNRTI Non-nucleoside reverse transcriptase inhibitors NRTI Nucleoside/nucleotide reverse transcriptase inhibitors NSS National Services Scotland NTS Non-typhoidal Salmonella OPAT Out-patient parenteral antibiotic therapy OR Odds Ratio OXA Oxacillinase PCR Polymerase Chain Reaction PHE Public Health England PI Protease Inhibitors PID Pelvic Inflammatory Disease PPS Point Prevalence Survey PUO Pyrexia of unknown origin PWID People who inject drugs RTI Respiratory Tract Infection SAC Scottish Agricultural College SAPG Scottish Antimicrobial Prescribing Group SBSTIRL Scottish Bacterial Sexually Transmitted Infections Reference Laboratory SCOTMARAP Scottish Management of Antimicrobial Resistance Action Plan ScRAP2 Scottish Reduction in Antimicrobial Prescribing version 2 SDCEP Scottish Dental Clinical Effectiveness Programme SDRM Surveillance Drug Resistance Mutations SEAG Scottish Environmental AMR Group SFC-1 Serratia fonticola carbapenemase-1 SHAIPI Scottish HAI Prevention Institute SHLMPRL Scottish Haemophilus, Legionella, Meningococcus and Pneumococcus Reference Laboratory SICPs Standard Infection Control Precautions SMiRL Scottish Microbiology Reference Laboratories SMRSARL Scottish Meticillin Resistant Staphyloccus aureus Reference Laboratory SMVN Scottish Microbiology and Virology Network SONAAR Scottish One Health Antimicrobial Use and Antimicrobial Resistance Report SPSP Scottish Patient Safety Programme SRUC Scotland s Rural College SSIs Surgical Site Infections SSSCDRL Scottish Salmonella, Shigella and Clostridium difficile Reference Laboratory STI Sexually Transmitted Infection SUTIN Scottish Urinary Tract Infection Network TBPs Transmission Based Precautions TDR Transmitted Drug Resistance UKAS UK Accreditation Service UTI Urinary Tract Infection VADs Vascular Access Devices VIM Verona integron encoded metallo-beta-lactamases VRE Vancomycin-resistant enterococci WGS Whole Genome Sequencing WHO World Health Organisation vi

9 Introduction Antimicrobial resistance (AMR) is the ability of microbes (bacteria, viruses, fungi and parasites) to withstand the effects of antimicrobials (chemical agents used to suppress or kill microbes). There is a risk of resistant microbes emerging during antimicrobial use, complicating the treatment of patients with infection. Whilst the acquisition of AMR is an evolutionary phenomenon, the misuse of antimicrobials in humans and animals sustains and amplifies AMR. 1 The increase in antimicrobial use over the last seventy years has increased levels of AMR, to such an extent that resistance has become a global crisis with the advent of: multi-drug resistant infections which are difficult, or in some cases, impossible to treat with antimicrobials, with resultant poorer outcomes for patients, higher rates of infection as difficult to treat episodes of resistant infections last longer, providing a greater opportunity for spread, higher healthcare costs as more expensive treatments, and longer hospital stays, are required, increased risk associated with procedures such as major surgery, transplants, and chemotherapy. 1,2 Moreover, these AMR impacts are heightened by ongoing: demographic change, resulting in an older population often with comorbidities, 3 shift of care from acute to community healthcare settings, increasing the risk of healthcare associated infection (HCAI) from non-hospital care, 4 medical advances, including more complex invasive interventions, increasing the risk of invasive infections. 5 In summary, as patients become increasingly vulnerable, and complex invasive procedures more common, modern medicine relies more than ever on the availability of effective antibiotics. This increasing threat from AMR, in the context of the decline in development of new antimicrobials, led to the UK Government s Five Year Antimicrobial Resistance Strategy (2013 to 2018) 6 which aimed to: improve knowledge and understanding of AMR, conserve and steward the effectiveness of existing treatments, and stimulate the development of new antibiotics, diagnostics and novel therapies. In 2014, the Scottish Government commissioned Health Protection Scotland (HPS) and partners (the Scottish Antimicrobial Prescribing Group (SAPG), and NHS Education Scotland (NES)), to develop and deliver a Scottish AMR strategy-controlling Antimicrobial Resistance in Scotland (CARS)- and refreshed the Scottish Management of Antimicrobial Resistance Action Plan (SCOTMARAP) ( ). 7 Additionally, as it is recognised that AMR is ultimately the product of a complex web of multilayered, interacting pathways and drivers in relation to humans, animals and the environment, HPS developed the change programme, CARS which adopts a One Health approach, considering AMR and its causes in all settings, and encouraging collaborations across human, animal and environmental spheres for the development and implementation of cross cutting, sustainable AMR control. 8,9 In short, the control of AMR is everyone s business. It is crucial, 1

10 therefore, that measures are taken to prevent infection, preserve the usefulness of antimicrobials, and control AMR in all human, animal and environmental settings. If not, the prospect of a postantibiotic age, where bacteria are resistant to antimicrobials, leading to many routine healthcare procedures becoming impossible or more dangerous, will become a reality. 1 Figure 1: Antimicrobial resistance: Interactions between humans, animals, food, and the environment. Humans Human Food Hospitals GPs, Care home & the community Food Direct contact Environment Water Human waste Crops Food Direct contact Direct contact Direct contact Animals Food Food Food animals Direct contact Land Animal waste Companion animals Wildlife Food for animals Direct contact One way Two way interaction This Scottish One Health Antimicrobial Use and Antimicrobial Resistance Report (SONAAR) replaces the previous Scottish AMR and Antimicrobial Use (AMU) Report. For the first time, consistent with the recommendations of the UK Five Year Antimicrobial Resistance Strategy, 6 and the One Health ethos, SONAAR includes: AMU data relating to: antibiotics and antifungals, in primary and secondary care, AMU by doctors, nurses, dentists and pharmacists. AMR data relating to: Gram-negative HCAIs (Acinetobacter spp, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Pseudomonas aeruginosa), Gram-positive HCAIs (Enterococcus spp. and Staphylococcus aureus), Sexually transmitted infections/bloodborne viruses (Neisseria gonorrhoeae and human immunodeficiency virus (HIV), Gastro-intestinal infections including Salmonella (from human and animals), and Shigella, Veterinary clinical isolates for selected organisms, Veterinary surveillance of Escherichia coli. 2

11 It is anticipated that the report will underpin national and NHS board AMR containment plans, and that the wider array of AMU and AMR surveillance information presented will improve understanding of, and engagement with, the One Health agenda, among a more diverse range of stakeholders (including the public, patients and carers, animal owners, and clinical and veterinary professionals) for sustainable AMR control. Data methods and sources are located in Appendix. 3

12 Human Antimicrobial Use Antibiotic use in humans The main driver for the development of antimicrobial resistance is exposure to antibiotics; high levels of antibiotic use are correlated with high levels of resistance. 10 Resistance is a natural consequence of using antibiotics; however, overuse and inappropriate use can unnecessarily increase the development of resistance. Preservation of the effectiveness of antibiotics is vital as few new antibiotics are under development. The antimicrobial stewardship programme coordinated by the Scottish Antimicrobial Prescribing Group (SAPG) supports optimisation of antibiotic use via the reduction of clinically inappropriate and unnecessary prescribing. Surveillance data on antibiotic use underpin the development, implementation and evaluation of stewardship interventions. In Scotland, in 2016, the total use of antibiotics in humans was 26.0 defined daily doses (DDD) per 1000 population per day (DDD/1000/day); 3.0% lower than in 2012 (Figure 2). Primary care (excluding dental use) accounted for the majority of antibiotic use (79.8%), followed by acute hospitals (13.8%), dentists (3.7%), and non-acute hospitals (2.6%) (Figure 3). Figure 2: Total use of antibiotics in humans, DDD/1000/day, 2012 to DDD/1000/Day Year Figure 3: Total antibiotic use by prescriber type, DDD/1000/day, in % Dental Primary Care Care Secondary 13.8% Acute Hospitals 2.6% 79.8% Non-Acute GP, Nurse & Pharmacists 4

13 Penicillins accounted for 41.8% of antibiotic use in humans in 2016, followed by tetracyclines (25.5%), macrolides (14.2%), sulphonamides and trimethoprim (6.6%), and nitrofurantoin (3.8%). Of the penicillins, penicillins with extended spectrum (mostly amoxicillin) was the group most used, accounting for 25.1% of antibiotic use, followed by beta-lactamase resistant penicillins (mainly flucoxacillin) (8.0%), co-amoxiclav (4.6%), beta-lactamase sensitive penicillins (phenoxymethylpenicillin and benzylpenicillin) (3.9%) and pipeperacllin-tazabactam (0.2%) (Figure 4). Figure 4: Usage by antibiotic class in % 2.9% 0.7% 0.3% 1.7% 3.8% 1.1% 25.5% 14.2% 6.6% 0.2% 1.0% 0.0% 0.2% 4.6% 8.0% 3.9% 25.1% Tetracyclines Penicillins with extended spectrum Beta-lactamase sensitive penicillins Beta-lactamase resistant penicillins Co-Amoxiclav Piperacillin-Tazobactam Other Penicillin combinations Cephalosporins Carbapenems Sulphonamides and Trimethoprim Macrolides Clindamycin Aminoglycosides Fluoroquinolones Glycopeptide antibiotics Imidazole derivatives Nitrofurantoin Other Data from 2015 published by the European Centre for Disease Prevention and Control (ECDC) illustrate how antibiotic use in Scotland compares with that of a selection of European countries (Figure 5). 11 There are, however, limitations in making direct inter-country comparisons due to differences in patterns of prescribing, disease burden, health systems and data availability. Figure 5: Use of antibiotics (DDD/1000/day) 2015 by European Country. DDD per 1000 inhabitants and per day Netherlands Estonia Latvia Slovenia Norway Hungary Denmark Lithuania Finland UK 5 Country Bulgaria Portugal Croatia Malta Scotland Slovakia Ireland Poland Luxembourg Italy Belgium Cyprus France Romania Greece An infographic to accompany Antibiotic use in humans of the SONAAR is available to download.

14 Antibiotic use in primary care In Scotland, in 2016, 79.8% of antibiotic use occurred in primary care (excluding dental use). The priority for preserving the effectiveness of antibiotics in primary care is minimisation of unnecessary antibiotic prescribing. The most common reason for prescribing antibiotics in primary care is respiratory tract infection (RTI) which accounts for around 60% of all antibiotic prescriptions; however, there is evidence that antibiotics offer no benefit to most people consulting with RTI. 12 This focus on reducing overuse of antibiotics is consistent with the Scottish Chief Medical Officer s vision for Realising Realistic Medicine with its aims to reduce harm and waste, tackle unwarranted variation in care, manage clinical risk and innovate to improve. 13 The use of systemic antibiotics (excluding dental use) was 2.0 items per 1000 population per day (items/1000/day) in 2016; 1.7% lower, and 35,173 fewer items, than in This is the fourth consecutive annual reduction, 11.1% lower than the peak rate of antibiotic use observed in 2012, and lower than at any point since 2004 (Figure 6). The proportion of the Scottish population which received antibiotics in primary care continued to decrease. In 2016, 29.0% of the population received at least one antibiotic item compared with 29.6% in 2015, the lowest proportion since data became available in Figure 6: Antibiotic use in primary care, items/1000/day, 2012 to of population prescribed 29% an antibiotic in Items/1000/Day Year The rate of antibiotic use varies by patient age. In 2016, in persons aged 0-4 years, 35.2% received at least one antibiotic. Since 2012, there has been a 22.2% reduction in the rate of antibiotic use in this age group. While there are no data on indication for antibiotic use available, antibiotics recommended for upper and lower respiratory tract infection (penicillins and macrolides) accounted for 66.8% of antibiotic use in this age group. The reduction in total antibiotic use in persons aged 0-4 years has been predominately driven by reduced use of these antibiotics, suggesting fewer prescriptions for common self-limiting infections. In contrast, in 2016, in persons aged 75 years, 45.2% received at least one antibiotic. Since 2012 there has been a 2.4% reduction in the rate of antibiotic use in this age group. Antibiotics recommended for urinary tract infection (UTI) accounted for 31.7% of antibiotic use in this age group (Figure 7). 6

15 Figure 7: Antibiotic use in primary care, items/1000/day, by age group, 2012 and Items/1000/Day % Reduction 2.4% Reduction Age group A national quality indicator a measure developed to indicate the quality of a healthcare service for primary care antibiotic use was introduced in 2013 to act as a stimulus for reductions in antibiotic use. A best in class methodology was used; to meet the quality indicator general practices must either achieve an equivalent or lower, prescribing rate than that of the Scottish 25th percentile or achieve an acceptable minimum reduction towards that level. To drive further improvement, the target prescribing rate was reset to use data from January - March A total of 57.3% of general practices, and ten of 14 NHS boards achieved this new target in January - March While progress has been made towards reducing antibiotic use in primary care, further reductions are possible. As a catalyst to further reduce antibiotic use, a phased programme to provide general practices in four NHS boards with reports of their rates of antibiotic prescribing compared with benchmarks for, i) their NHS board, and ii) Scotland, was developed. These reports contained suggested improvement action and details of available support resources. This initiative is based on two studies: one in which general practitioners (GPs) were provided with information on high risk medicines, and another in which dentists were provided with antibiotic prescribing data. 14,15 It is hypothesised that reports containing feedback of antibiotic prescribing data in conjunction with action-orientated goal setting text, delivered by to general practices, will reduce antibiotic prescribing compared with practices which do not receive the reports. A formal evaluation of the programme will commence in 2018 and, if shown to be effective, the intervention will be extended to include all general practices in Scotland. The reduction in primary care antibiotic use since 2012 suggests that clinicians and the public are working together to reduce unnecessary prescribing; however, clinicians may be concerned that initiatives to reduce antibiotic use could potentially result in patients with serious bacterial infections not receiving appropriate treatment. While antibiotic use amongst the general population has decreased, antibiotic prescribing amongst patients admitted to hospital with severe RTI has increased. This finding provides reassurance that patients who need antibiotics are receiving them, and supports further optimisation of prescribing in primary care. 16 In 2016, there was a continued shift in the type of prescribers responsible for antibiotic use. While GPs remained accountable for the majority (85.4%) of antibiotic use, the contribution of nurse prescribers continued to increase with a 21.9% increase in antibiotic use (items/1000/ day) compared with 2015 (Figure 8). In 2016, nurse prescribing accounted for 6.8% of antibiotic use in primary care, the highest proportion on record. Nurses prescribe a relatively limited range of antibiotics, with the ten most frequently prescribed antibiotics accounting for 96.2% 7

16 of nurses antibiotic prescriptions. Moreover, 92.6% of antibiotics prescribed by nurses are those recommended for empirical treatment of commonly encountered infections in primary care (RTI, UTI and skin infections) reflecting good compliance with local antibiotic policy recommendations. The National Clinical Strategy for Scotland highlights the central role of primary care in transforming service delivery in NHSScotland. The Scottish Government s vision for nursing 17 intends to transform nursing roles, a change which, in conjunction with newly proposed Nursing and Midwifery Council (NMC) 18 standards for preparing all graduate nurses as prescribing ready, will have a direct impact on antibiotic use. With increasing numbers of nurse prescribers it is likely that nurse prescribing of antibiotics will overtake dental prescribing of antibiotics in the near future; therefore, it is important that nurses and nurse prescribers are included in national and local antimicrobial stewardship activity. Figure 8: Antibiotic prescribing by nurses in primary care, items/1000/day, 2012 to Items/1000/Day Year In 2016, pharmacist prescribers accounted for antibiotics (0.2%), of total antibiotic use. With changing models of service delivery in primary care resulting in greater numbers of pharmacist prescribers working in clinical roles in general practice and other primary care settings, it is likely that pharmacist prescribers will exert an increasing influence on antibiotic use in the future. As such, pharmacists should be included in national and local antimicrobial stewardship initiatives. Dental prescribing accounted for 7.6% of antibiotic use in primary care in For more details on dental use of antibiotics see Antibiotic use in dentistry in primary care in Scotland. Most infections encountered in primary care are treated empirically, that is, where the prescriber has no definitive information on the organism or its antibiotic susceptibility. To support clinicians in primary care to optimise antibiotic use, SAPG and NHS Board Antimicrobial Management Teams (AMTs) have developed treatment policies based on evidence-based templates produced by Public Health England (PHE). 19 These local treatment policies are available through the Antimicrobial Companion application (app) and provide clinicians with advice on antibiotic choice and duration of treatment. They are intended to optimise antibiotic use through reducing unnecessary use of broad spectrum antibiotics. Antibiotics recommended for empirical treatment of commonly encountered infections in primary care accounted for 81.5% of total antibiotic use in This is similar to 2012 (81.2%) and suggests clinicians are following local prescribing policies. 8

17 Reducing the use of specific broad spectrum antibiotics (cephalosporins, co-amoxiclav and fluoroquinolones) is an important element of primary care antimicrobial stewardship. In 2016, these broad spectrum antibiotics accounted for 8.0% of total antibiotic use similar to 2015 (8.1%). Use of cephalosporins (7.3%) and fluroroquinolones (1.9%) appear lower in 2016 compared with For the first time since 2007, there was an increase in co-amoxiclav use (2.2%). AMTs should carefully monitor local use of co-amoxiclav to identify practices with higher rates of use of this broad spectrum antibiotic. A recent study described the association between antibiotic use in primary care and community associated Clostridium difficile infection (CA-CDI). Individuals with 29 DDD (an approximation for 29 days of treatment) of any antibiotic in the previous six months had more than four times the risk of CA-CDI compared with no antibiotic exposure. 20 Further, among individuals exposed to 29 DDD of high-risk antibiotics (cephalosporins, clindamycin, coamoxiclav or fluoroquinolones) this risk was higher (odds ratio (OR) 17.9). Elevated CA-CDI risk following exposure to high-risk antibiotics was greatest in the first month and continued for four to six months. These findings are being used to develop clinical decision support tools as part of the work of the Scottish HAI Prevention Institute (SHAIPI). The second most common reason for antibiotic use in primary care is UTI. 21 In Scotland, nitrofurantoin and trimethoprim are recommended for the empirical treatment of uncomplicated UTI. 22 In 2016, use of these antibiotics accounted for 19.4% of total antibiotic use in primary care. Since 2012, there has been a 20.0% increase in the use of nitrofurantoin and a 2.6% reduction in trimethoprim use. The number of prescriptions with a three-day duration as a proportion of all prescriptions for nitrofurantoin or trimethoprim in adult females is a measure of compliance with prescribing guidelines. Three-day courses represented 40.0% of all nitrofurantoin prescriptions in 2016, compared with 24.0% in Use of three day courses of trimethoprim accounted for 58.1% of all trimethoprim items for adult females, compared with 49.5% in In 2018, an investigation of repeat antibiotic courses to assess potential differences between patients receiving three-day and longer courses of nitrofurantoin and trimethoprim will be undertaken. Multi-drug resistance (MDR) in urinary pathogens reduces treatment options, and may increase treatment failures as it renders initial empirical treatment ineffective. Additionally, it has the potential to drive the use of broad spectrum antibiotics, hence the generation of yet more resistant organisms. A National Services Scotland (NSS) study using data linkage identified risk factors for resistance in urine isolates, and demonstrated an association between nitrofurantoin or trimethoprim use and development of resistance including MDR. 23 This analysis provides evidence of a cumulative and sustained impact of antibiotics commonly used for UTI on MDR. Male gender, increasing age and co-morbidity, prior hospitals stays and care home residence were associated with increased risk of resistance after adjustment for other factors. This evidence is informing the development of personalised prescribing decision support tools based on individual patient characteristics and previous antibiotic treatment. In 2016, SAPG and NES launched, a Scottish Reduction in Antimicrobial Prescribing version 2 (ScRAP2) programme which contributes to the UK strategic aim of, Improving professional education, training and public engagement. This learning resource was updated to include information on optimising prescribing in: i) uncomplicated UTI in females, ii) complicated UTI in older people, iii) catheterised patients, iv) males and, v) recurrent UTI, and will support clinicians to optimise management of UTI. An infographic to accompany Antibiotic use in primary care of the SONAAR is available to download 9

18 Antibiotic use in acute hospitals The preservation of the effectiveness of antibiotics for the treatment of infections in hospitalised patients involves balancing the use of antibiotics to ensure the best clinical outcomes for patients with minimising the risk they present to, i) patients receiving antibiotics and, ii) the wider population through the development of resistance. It is clear, therefore, that consistent with the aims of the Realistic Medicine approach ensuring rational, safe and effective use of antibiotics is the responsibility of all clinicians. In Scotland, in 2016, 13.8% of total antibiotic use in humans was within acute hospitals. Over the last five years, there has been an increasing trend in antibiotic use in acute hospitals. Antibiotic use expressed as DDD per 1000 admissions (ADM) was 10.2% higher in 2016 compared with 2012 (Figure 9). Figure 9: Antibiotic use in humans within acute hospitals, DDD/1000ADM, 2012 to DDD/1000ADM Year In 2012, 28.7% of antibiotics used in acute hospitals were given by injection and this has increased year on year to 32.1% in This observation may be as a result of initiation of prompt antibiotic treatment in patients with suspected sepsis following implementation of Sepsis Six and other initiatives to improve the recognition and management of sepsis. 24 The National Point Prevalence Survey (PPS) of HCAI and Antimicrobial Prescribing 2016 reported a prevalence of antimicrobial use in adults of 35.7%. 25 Taking account of differences in patient, age and case mix between this and the previous survey, prevalence was significantly higher in 2016 compared with 2011 (33.2% adjusted OR=1.11, 95% CI: 1.02 to 1.21, p=0.01) consistent with the increased rate of antibiotic use in acute hospitals in 2016 expressed as DDD/1000ADM. Antibiotic prescribing guidelines in acute hospitals are the source of advice for clinicians regarding empirical treatment of commonly encountered infections. Interventions to improve the recording of the reason for antibiotic treatment in patient records, and to maximise coherence of treatment choice with local prescribing policy, are in place. In 2016, the PPS reported improvement since 2012 in recording the reason for antibiotic use (94.8% v 89%) and compliance with local policy (87.2% v 82.5%). 25 While these findings suggest improved quality of antibiotic use, there is a need to focus on the quantity of antibiotics used. The challenge for preservation of antibiotics in acute hospitals is to safely reduce antibiotic use to minimise selection pressure for AMR, while maintaining positive outcomes for patients. 10

19 Initially, the priority for stewardship programmes was to optimise antibiotic prescribing through reducing the use of broad spectrum antibiotics (such as cephalosporins, ciprofloxacin, clindamycin and co-amoxiclav) associated with an increased risk of CDI. These antibiotics became known collectively as the 4Cs. AMTs successfully engaged clinicians with a 4C focussed stewardship programme to reduce the use of these antibiotics. While CDI remains an important HCAI, the infection landscape has changed since 2008 and the threat from drug resistant infections, in particular those due to MDR Gram-negative bacteria, has become an additional priority for clinicians managing patients with, or at risk of infection. There is a need to balance the benefits of early antibiotic treatment in suspected sepsis with CDI prevention and interventions to preserve the effectiveness of antibiotics against Gram-negative drug resistant infection. Emerging stewardship models being developed in Scotland recognise the importance of clinicians embedding work to preserve the effectiveness of antibiotics into routine care. The essential elements of this evolving model are based on four stewardship themes. These themes may be considered together as the 4Ds : Duration ensure that patients are not continued on antibiotics for longer than is clinically necessary. De-escalate using narrower spectrum agents, used alone or in combination, in accordance with microbiology results and/or with clinical improvements in patients symptoms. Discontinue stopping antibiotics as soon as infection is no longer the working diagnosis. Diversify recognising the need to balance homogeneity of antibiotic use with using particular antibiotics in specific clinical situations and adopting a patient centred approach in terms of antibiotic choice, dose and duration. In 2016, the national antimicrobial stewardship programme developed a 4D focus to reduce total antibiotic consumption through prompt de-escalation and switch to oral treatment as soon as clinically appropriate, together with stopping antibiotics when infection has been excluded. Consequently, patient exposure to unnecessary antibiotics should be reduced. In 2016, the PPS reported 48.4% of antibiotics given by injection had been given for more than three days and 14.8% had been given for more than seven days. 25 Moreover, 14.3% of oral antibiotics had been prescribed for more than seven days. In 2016, a national quality indicator was developed to reduce antibiotic use by at least 1% and drive improvement in antimicrobial stewardship in acute hospitals by encouraging clinicians to: undertake review of patients receiving intravenous antibiotics within 72 hours of treatment commencing, and to document the outcome of this review, and record the intended duration of treatment for patients prescribed oral antibiotics. The Antimicrobial Companion app, has been further developed to enable the collection of data to support this national quality indicator. Initially data will be collected by AMTs and shared with clinicians; however, it is envisaged that this audit tool will help to embed stewardship activity into routine clinical practice through data collection, review and feedback to frontline clinicians. In 2018, a toolkit to support clinicians embed a 72 hour review into routine clinical practice will be developed. These initiatives will support the clinician-led approach to the preservation of antibiotics in hospitals. 11

20 The Scottish Government is committed to developing a single national medicines formulary for Scotland to deliver consistency, equity and value for money. SAPG and the Scottish Microbiology and Virology Network (SMVN), have commenced work to deliver a national guidance template for hospital antibiotic prescribing. There is already a high degree of consistency among NHS boards, and this work may enable the removal of redundant and unnecessary antibiotics from some regimens together with the increased use of narrower spectrum antibiotics; this strategy is consistent with the CMO s Realistic Medicine approach. In 2016, 70 different antibiotics were used in acute hospitals. Five antibiotics accounted for 63.0% and ten accounted for 81.6% of total antibiotic use (Figure 10). Figure 10: Top ten antibiotics used in acute hospitals in % 22.2% 2.5% 3.3% 3.8% 4.4% 13.7% 4.6% 7.3% 7.6% 12.2% Amoxicillin Co- amoxiclav Flucloxacillin Clarithromycin Doxycycline Metronidazole Ciprofloxacin Gentamicin Trimethoprim Co-trimoxazole Other In 2016 the use of key antibiotics was as follows: Co-amoxiclav Co-amoxiclav use accounted for 13.7% of total antibiotic use in acute hospitals. Use of coamoxiclav was DDD/1000ADM; 2.1% lower than in 2015 and a second successive annual reduction. Fluoroquinolones Ciprofloxacin was the most commonly used fluoroquinolone antibiotic, accounting for 4.4% of total acute hospital antibiotic use. Use of ciprofloxacin was DDD/1000ADM in 2016 and after two successive annual reductions is 5.1% lower than in In contrast, the use of levofloxacin, which is indicated for the treatment of pneumonia in patients with reported penicillin allergy, has increased year on year since Use of levofloxacin was 79.5 DDD/1000ADM in 2016 compared to 33.3 DDD/1000ADM in Cephalosporins Restriction of the use of cephalosporins was a central component of 4C based stewardship interventions. Cephalosporin use accounted for 2.1% of total antibiotic use in acute hospitals in Use of cephalosporins was DDD/1000ADM in 2016 compared with DDD/1000ADM in Cephalosporins are not a homogenous group with respect to their potential therapeutic uses and risk of CDI. Certain cephalosporins may be considered in specific patient groups. For example, ceftriaxone, a third generation cephalosporin, is a useful 12

21 component of out-patient parenteral antibiotic therapy (OPAT) services, where its single daily dose may enable the prevention of admission or early discharge of patients who require parenteral antibiotics. Since 2012 there has been an increase of 43.3% in ceftriaxone use to 46.3 DDD/1000ADM in Narrow spectrum penicillins There have been steady reductions in the use of the narrow spectrum beta-lactamase sensitive penicillins. Since 2012 there has been a decrease of 10.7% in benzylpenicillin use to 54.6 DDD/1000ADM and 30.5% in phenoxymethylpenicillin use to 74.3 DDD/1000ADM in In the context of the threat from resistance, the use of these two narrow spectrum antibiotics as part of monotherapy or combination therapy should be reconsidered. Doxycycline The use of doxycycline which is recommended for treatment of RTIs such as community acquired pneumonia, and infective exacerbation of chronic obstructive pulmonary disease, accounted for 7.3% of total antibiotic use in acute hospitals in Since 2012, there has been a 32.5% increase in doxycycline use to DDD/1000ADM in Gentamicin In Scotland, gentamicin, in combination with other antibiotics, is recommended for treatment of sepsis of unknown origin, intra-abdominal, and urosepsis. Its use increased following interventions to restrict the use of antibiotics associated with a higher risk of CDI. In 2016, gentamicin accounted for 3.8% of total antibiotic use in acute hospitals. Since 2012, there has been a 15.0% increase in gentamicin use to DDD/1000ADM in Metronidazole In 2016, metronidazole accounted for 4.6% of total antibiotic use in acute hospitals and was the sixth most commonly prescribed antibiotic. Since 2012, there has been a 14.0% increase in metronidazole use to DDD/1000ADM. The place of metronidazole within empirical prescribing guidelines for pyrexia of unknown origin should be reviewed based on an assessment of the need for empirical treatment to cover anaerobes. Flucloxacillin Flucloxacillin is primarily used to treat skin and soft issue infections thought to be caused by meticillin susceptible Staphylococcus aureus (MSSA). In 2016, flucloxacillin accounted for 12.2% of total antibiotic use in acute hospitals and was the third most commonly prescribed antibiotic. Since 2012, there has been an 11.1% increase in flucloxacillin use to DDD/1000ADM in Glycopeptides Glycopeptides such as parenteral vancomycin and teicoplanin are used to treat infections suspected to be caused by Gram-positive organisms, in particular where meticillin resistant Staphylococcus aureus (MRSA) may be suspected. Parenteral vancomycin use accounted for 1.2% of total antibiotic use in acute hospitals in Since 2012, there has been an 18.5% increase in parenteral vancomycin use to 70.3 DDD/1000ADM in In 2016, teicoplanin use accounted for 0.7% of total antibiotic use in acute hospitals and since 2012 increased by 20.2% to 40.2 DDD/1000ADM in While reducing total antibiotic exposure has been the priority to reduce selection pressure for resistance, an additional focus was to optimise use of very broad spectrum antibiotics which are vitally important for the treatment of MDR infections. Increased use, particularly inappropriate use, of antibiotics such as carbapenems and piperacillin/tazobactam can select resistant pathogens; therefore, quality improvement programmes to preserve the effectiveness 13

22 of these antibiotics are in place. In 2016, carbapenems accounted for 1.2% of total antibiotic use in acute hospitals. Between 2012 and 2015 there was an increasing trend (8.8%) in carbapenem use; however, in 2016, the use of carbapenems was 72.4 DDD/1000ADM, 11.8% lower compared with Moreover, carbapenem use in 2016 was 4.0% lower than in 2012 (Figure 11). In contrast the PPS 2016 reported the prevalence of carbapenem prescribing in acute adult patients was not significantly different 2016 and Figure 11: Carbapenem use in humans within acute hospitals, DDD/1000ADM, 2012 to DDD/1000ADM Year Piperacillin/tazobactam use accounted for 1.7% of total antibiotic use in acute hospitals in In 2016, the use of piperacillin/tazobactam was 13.3% lower than in 2015, the second successive annual reduction in use. Use of piperacillin/tazobactam in 2016 was DDD/1000ADM, 7.2% lower than in 2012 (Figure 12). The PPS 2016 reported the prevalence piperacillin/tazobactam prescribing of between 2016 and 2011 was not significantly different in acute adults. 25 Figure 12: Piperacillin and tazobactam use in humans within acute hospitals, DDD/1000ADM, 2012 to DDD/1000ADM Year The reduction in use of these very broad spectrum antibiotics suggests that quality improvement interventions may have been embraced by clinicians across NHSScotland. In 2017, the Scottish Government developed a national quality indicator for a reduction of at least 1% in the use of carbapenems and piperacillin/tazobactam to act as a stimulus for optimisation of use of these antibiotics. 14

23 An important component of engaging clinicians to change prescribing behaviours, particularly with respect to very broad spectrum antibiotics, has been to advise on alternative antibiotics for infections thought to be caused by Gram-negative organisms. In 2016, guidance to reduce MDR Gram-negative infections which promoted the use of aztreonam, pivmecillinam and temocillin as alternatives to carbapenems was updated. 26 In 2016, use of these alternatives remained low. Aztreonam accounted for 0.4% of total antibiotic use in acute hospitals; temocllin 0.4%; and pivmecilliam 0.1%. Aztreonam use in 2016 was 24.8 DDD/1000ADM similar to 2015 (26.0 DDD/1000ADM). In 2016, there were problems obtaining supplies of aztreonam which resulted in AMTs increasing use of temocillin. Use of temocillin increased from 5.4 DDD/1000ADM in 2015 to 23.4 DDD/1000ADM in Prescribing policies and supporting educational activities were important factors in the promotion of the use of these carbapenem sparing antibiotics. In summary, the current interventions to optimise antibiotic use in humans across Scotland appear to be working in part, with continued progress in reducing unnecessary antibiotic use in primary care, and some improvements in acute hospitals. However the total prescribing burden in hospital is higher, so there is no time for complacency. The improvements to date must be consolidated and built upon and the pace of improvement accelerated by moving to clinician-led antibiotic stewardship ensuring the work of preserving the effectiveness of antibiotics becomes everyone s business. An infographic to accompany Antibiotic use in acute hospitals of the SONAAR is available to download Antibiotic use in dentistry in primary care in Scotland Dentists can prescribe a limited range of antibiotics on NHS prescriptions (GP14) in primary care in Scotland comprising: amoxicillin; azithromycin; cefalexin; cefradine; clarithromycin; clindamycin; co-amoxiclav; doxycycline; erythromycin; metronidazole; oxytetracycline; phenoxymethylpenicillin and tetracycline. The Scottish Dental Clinical Effectiveness Programme (SDCEP) has developed Drug Prescribing in Dentistry guidance 27 to provide advice on dental prescribing relevant to primary care dental practice. It recommends that antibiotics are appropriate for oral infection where there is evidence of spreading infection (cellulitis, lymph node involvement, swelling) or symptoms such as fever or malaise that suggest systemic involvement. The SDCEP guidance emphasises the role of diagnostic accuracy and surgical management of infection sources using root canal therapy, extraction or incision and drainage where clinically applicable. Other indications for antibiotics are acute ulcerative gingivitis and pericoronitis where there is systemic involvement or persistent swelling despite surgical interventions. Dental practitioners have an important role in the management of sinusitis by managing dental sources of pain and infection that could contribute to misdiagnosis. In 2016, there were antibiotics dispensed on dental prescriptions, the lowest total annual number of dental antibiotic prescriptions in the last 20 years. Antibiotic use by dentists in 2016 was 0.16 items/1000/day, 5.9% lower than in This continues the reducing trend since 2012 (Figure 13). Since 2012 there has been a 23.9% reduction in antibiotic use in dentistry. Advice in 2015 that antibiotic prophylaxis against infective endocarditis is not routinely recommended for people undergoing dental procedures may have contributed to this reduction in dental antibiotic use. 15