1 TARGET Antibiotics 1. The top part of this notes section is for presenters to use during the workshop, and can be used verbatim or paraphrased. Extra notes below contain extra background information about the evidence base for the information on the slides and details about the references quoted, or how to obtain particular information or resources. Underlined notes are instructions. If you want to use the voice over at any time please make sure your laptop or PC has functional speakers and they are not on mute. While you are waiting for staff to arrive it is really useful to get them to think about their current antibiotic prescribing practice by getting them to complete the self-assessment checklist available at (see slide 2) Giving them the TARGET patient leaflet to look at (available at ) Print out and ask the group to consider and chat about some of the case studies in the presentation. Lets begin! Slide one presenter notes: I hope you all agree with the UK Chief Medical Officer, Dame Sally Davies, that “There are few public health issues of potentially greater importance for society than antibiotic resistance” but lets take a moment to reflect. Next slide. “There are few public health issues of potentially greater importance for society than antibiotic resistance” 2013 CMO Prof Dame Sally Davies Version 2 Published online: July 2017 Review date: July 2019 TARGET Antibiotics Presentation - Main

2 TARGET: Self Assessment Checklist to complete whilst waiting for whole team9 December, 2017 Presenter notes: We suggest you send this to practice staff before the event or give it out as soon as you arrive – while you are waiting for all staff to gather. Go through self-assessment check list with the staff, this acts as a very good ice breaker and can be referred back to during the session. The Primary Care Self Assessment tool is a tool for you to decide and measure how far you are along the road to optimising antibiotic prescribing in your practice. It highlights the different strategies you can use and how you can find resources to support these strategies. This tool is a guide to providing strategies that may help to optimise antibiotic prescribing in primary care. There is also a separate part for commissioners which it would be useful for trainers to access and complete to see how well their local area is doing. Presenter notes – we suggest at this point you get them to have a quick look to see how many of the 13 strategies they are using to optimise antibiotic prescribing in their practice. Make sure you are familiar with the local antibiotic guidance and how they can access it, how you can help with audits, and Read codes. Encourage the practice to identify a lead for prescribing, and if possible book another visit to go over their progress with local indicators of antibiotic prescribing and their use of the resources. Encourage the practice again to use leaflets and posters and if possible put some antibiotic posters up while you are there. Are the laboratory protocols for reporting antibiotic susceptibility in line with local antibiotic guidance. TARGET Antibiotics Presentation - Main

3 Aims of this workshop Brief background9 December, 2017 Brief background Discuss some clinical cases where we could improve our antibiotic prescribing Suggest strategies and share materials Show the evidence for using the materials Provide evidence showing the link between antibiotic prescribing and resistance in your patients Show how reducing antibiotic prescribing can reduce antibiotic resistance, and also patient consultations Presenter notes: The aims of this workshop are to discuss with you, using clinical scenarios, the need for optimising antibiotic prescribing, by showing you the: evidence that there is a link between antibiotic prescribing and resistance in GP patients how reducing antibiotic prescribing can not only reduce antibiotic resistance, but also patients’ future expectations for an antibiotic and a consultation. We will also discuss and share materials and strategies (and the evidence behind them) that can help us together with our hospital and veterinary colleagues improve our antibiotic prescribing TARGET Antibiotics Presentation - Main

4 Context 9 December, 2017 If we don’t tackle drug resistant infections now, they could kill an extra 10 million people across the world each year by 2050. In the UK, 80% percent of antibiotic prescribing occurs in the community. So, there is much information out there about the threat and consequences of antimicrobial resistance. We know that around 80% of antibiotic prescribing takes place in primary care and many of these are for respiratory tract infections. There have been a number of initiatives and developments at a national level to get people thinking more responsibly about antibiotic prescribing. NICE issued guidance on Antimicrobial Stewardship (NG 15); the NHS and Public Health England jointly issued a Patient Safety Alert around AMS; there are prescribing quality measures and incentives and the DH would like us to get back to the level of prescribing that we had in 2010. The TARGET Guide to Resources provides more detail on these measures, and the TARGET toolkit helps you to optimise your use of antibiotics. TARGET Antibiotics Presentation - Main

5 The Iceberg of Gram Negative ResistanceCarbapenemases<2% ESBL Sensitive Some resistance Presenter notes: On a daily basis we don’t see the results of multi resistant infections, as they are the tip of the iceberg. However there is much resistance hidden within the community setting. 7% of the general population in England in a 2014 stool collection survey carried Extended beta lactamase producing E.coli in their gut. And you all know from your daily practice that antibiotic resistance in UTIs is increasing to trimethoprim, even though these organisms may not be multiresistant Courtesy of Gavin Barlow

6 UK prescribing: 80% of antibiotics are prescribed in general practice9 December, 2017 UK prescribing: 80% of antibiotics are prescribed in general practice DDD / 1000 inhabitants/day Hospitals outpatients Hospital inpatients Dentists Other General practice Interviews with GPs indicate that: GPs recognise the wider importance of resistance But they don’t really think that it is a problem in their own practice And they believe that hospitals and other prescribers such as vets are as important or more important contributors to resistance. However this data shows that 80% of antibiotics are prescribed in the community and therefore GP staff hold much of the responsibility for rising use and antibiotic resistance. However this doesn’t mean that the other groups antibiotic prescribing is not important. In deed it is and that is why there is the Start Smart Then Focus strategy in hospitals, a campaign with dentists with posters saying “antibiotics do not cure toothache,” and a strategy to improve antibiotic prescribing in animals. The good news is that in 2015 we saw the first fall in antibiotic use in general practice for some years. ESPAUR 2015 TARGET Antibiotics Presentation - Main

7 Europe Prescribing: EU Community Antibiotic Consumption9 December, 2017 DDD per 1000 inhabitants per day (2015) Presenter notes: However we still have some way to go compared to some other European countries. Although as this slide shows in comparison to other European countries we prescribe much less than Greece, which has a major resistance problem, in the community we do prescribe twice as much as the Netherlands which has a similar population to us. I suggest therefore that there is an opportunity to reduce our community antibiotic prescribing. The differences are partially due to cultural norms in the UK compared to other Northern EU countries who prescribe less for respiratory tract infections. Extra presenter notes: The EU expresses community antibiotic consumption in Defined Daily Doses per inhabitants and per day, which is slightly different to the ADQs used in the UK. Each bar refers to a specific country while the colours indicate the recorded consumption of the different antibiotic classes in that country. Total community antibiotic consumption ranged from 11 DDD per inhabitants and per day in Netherlands to 37 DDD per 1,000 inhabitants and per day in Greece. As in previous years, antibiotics of the penicillin class were the most frequently used antibiotics in all countries . The UK still prescribes more than any of our northern European colleagues. DDDs (or if we used ADQs) is influenced by antibiotic dose, so as clinicians use of amoxicillin increases from 250 to 500mg routinely, the ADQs and DDDs increase, even if the number of items remains the same. © ECDC TARGET Antibiotics Presentation - Main

8 Prescribing: Your data May 2016 – May 20179 December, 2017 Prescribing: Your data May 2016 – May 2017 Total antibacterial Items/STAR-PU Vs Co-amoxiclav, Cephalosporin and Quinolone % Items Presenter notes:– Antibiotic prescribing data is available from the NHS England Antibiotic Quality Premium monitoring dashboard here: Or data is available from FingerTips: https://fingertips.phe.org.uk/ This is free to access on the NHS England web site and will be updated at the start of each month. You should be able to access prescribing data for your CCG and insert it onto this slide. This scatter plot shows the variation in total number of antibiotic items on the vertical Y axis, and the % of the total that the co-amoxiclav, cephalosporin and quinolone items make up, on the horizontal X axis. As you can see there is a wide variation in use in total items across England, but also here locally in this CCG (seen in the darker dots). There is an even greater variation in the use of co-amoxiclav, cephalosporins and quinolones. This dot represents where you fall in the distribution compared to others in this CCG and nationally. You are … [describe location on the chart] The variation suggests that there is an opportunity for you to decrease your prescribing. TARGET Antibiotics Presentation - Main

9 Antibiotic prescribing in Primary Care vs European Targets09/12/2017 Current Position % Median prescribing rates (1) EU Target prescribing rates % (2) Cough/bronchitis 48% 0 - 30% Sore throat 60% 0 – 20% Otitis media Sinusitis So where are we at the moment compared to where we want to get. There has been some good news about primary care antibiotic prescribing with rates having fallen by 5% since 2016 and 11% since 2011, but these studies show that GPs still prescribe antibiotics in more than half of all respiratory infections. Targets set by the European Surveillance on Antimicrobial Consumption suggest we still have a long way to go and that we need to reduce prescribing by 2/3rds. 1. 2. Adriaenssens N, Coenen S, Tonkin-Crine S, et al. European Surveillance of Antimicrobial Consumption (ESAC): disease-specific quality indicators for outpatient antibiotic prescribing. Quality and Safety in Health Care. TARGET Antibiotics Presentation - Main

10 Why do GP staff prescribe antibiotics?21/05/2014 Why do GP staff prescribe antibiotics? Relief of symptoms Worry about complications/more serious illness Patient pressure Presenter notes: So, how do we change antibiotic prescribing? Lets go back to the fundamentals of practice. Why do we prescribe? We prescribe mainly for 3 reasons. Firstly, we want to help our patients to get better. We want to relieve their symptoms and we believe that antibiotics will help. Secondly, we prescribe because we worry that if we don’t patients may develop complications or more serious illness. We also prescribe because we think patients expect a prescription, usually antibiotics. Let’s take look at these three reasons for prescribing and examine the evidence supporting each of these reasons.. TARGET Antibiotics Presentation - Main

11 Symptom benefit from antibioticsextra slides 21/05/2014 Symptom benefit from antibiotics Total Duration untreated Beneficial effect from antibiotics NNT for one additional patient to benefit NNT for one additional adverse effect Otitis media 4 -12 days 8-12 hours 18 9 Sore throat 8 days 12-18 hours 6-20 15 Sinusitis 12-15 days 24 hours 8 Bronchitis 20-22 days 11-24 hours 10-22 24 Presenter notes: How useful are antibiotics for common respiratory tract infections? This table includes much of the research on what we know about common respiratory tract infections, how long the symptoms usually last , and how much patients benefit from taking antibiotics. As you can see from the circled column antibiotics reduce symptoms for between 8 and 24 hours. So at best about 12 hours in otitis media, an illness that lasts for 4 to 8 days; taking a look at the NNT Benefit and NNT Harm columns – 18 patients with OM need to be treated with antibiotics for one patient to benefit, but for 9 patients receiving antibiotics one will experience an adverse effect. For bronchitis, an illness that lasts for about three weeks, the reduction in days with cough was less than half a day and the reduction in days feeling ill was just over half a day with antibiotics. Any benefit that our patients achieve from antibiotics is tiny and the numbers needed to treat to achieve one satisfactory earlier resolution needs to be weighed against the one in 10 chance of causing side effects such as diarrhoea, vomiting, rash, allergic reaction (1 in 15) or the risk of carrying a resistance bacteria. So, unless symptoms are particularly severe, there is no reason for using antibiotics in the majority of patients presenting with respiratory symptoms because they do not help. Evidence This evidence is all outlined in the PHE antibiotic guidelines and NICE CG69, but most recent systematic reviews include: Otitis media Venekamp et al (2015) Antibiotics for acute middle ear infection (acute otitis media). Cochrane This systematic review included 13 RCTs involving 3401 children with otitis media (3938 episodes). Pain was not reduced by antibiotics at 24 hours. A third fewer had residual pain at 2-3 days (at which point pain levels are usually substantially reduced) and NNT for an additional beneficial outcome was 20. Antibiotics reduced the number of Tympanic Membrane perforations, but NNT for Benefit is 33. Severe complications were rare and did not differ between children given antibiotics and those given placebo. Antibiotics are most beneficial for children aged <2 yrs with bilateral AOM (NNTB 4) or with both AOM and discharge (NNTB 3). Immediate antibiotics were associated with a substantial increased risk of vomiting, diarrhoea or rash compared with no treatment (NNTH9). Sore throat Spinks A et al. (2013) Antibiotics for sore throat. Cochrane 27 RCTs of antibiotics for sore throat vs placebo including cases. Antibiotics were most beneficial if given at day three if throat swabs were positive for streptococcus (NNTB 6) compared to NNTB at day 7 of 21. Antibiotics reduced duration of symptoms by 16 hours on average. 90% resolve in 7 days. Advantages may be greater in low income countries (possibly recent travelers from these countries – personal communication Dr L Hendricks) where the risk of rheumatic fever is higher. NNTH is 15. Little P et al (2013) – 2 studies within the PRISM trial used a Clinical score compared to rapid antigen detection test to guide antibiotic use for sore throats. The RCT using clinical scores to predict streptococcal infection in patients and found that the use of FeverPAIN is likely to moderately improve symptom control and reduce antibiotic use. PHE and NICE guidance suggests Consider immediate antibiotics if symptoms severe or a short 48 hour back-up strategy may be appropriate, when the FeverPAIN score is 4 or over. Consider back-up or no antibiotic if score 2-3. Sinusitis Leminengre M et al. (2012) Antibiotics for clinically diagnosed acute rhinosinusitis in adults. Cochrane. 10 RCTs of antibiotics vs placebo including 2450 participants. Irrespective of treatment group 47% of patients were cured after 1 week, 71% after 14 days. 18 patients need to be treated for a faster cure rate between 7 and 14 days. If several of: purulent nasal discharge; severe localised unilateral pain; fever; marked deterioration after initial milder phase, patients were more likely to benefit from antibiotics, when PHE and NICE recommend a back-up antibiotic. One disease related complication (brain abscess) occurred in patient treated with antibiotics, but complications are rare. Bronchitis/LRTI (without pneumonia) Smith S et al. (2014) Antibiotic treatment of people with clinical diagnosis of acute bronchitis. Cochrane 17 trials with 5099 participants were included. The number needed to treat for one additional beneficial outcome was 22 (NNTB 22). The reduction in days with cough was 0.46 days and days feeling ill was 0.64 days (CI ). NNT for an additional adverse effect was 24. And how do we communicate this information to patients? Cochrane reviews Otitis media: Venekamp et al (2015); Sore throat: Spinks et al. 2013; Sinusitis: Leminengre M et al. (2012); bronchitis: Smith et al. (2014) TARGET Antibiotics Presentation - Main

12 extra slides 09/12/2017 Complications with lower antibiotic use: High vs low prescribing practices In a practice of 7,000, a 10% reduction in antibiotic prescribing for RTI might expect: 1 additional pneumonia each year 1 additional peritonsilar abscess each 10 years Presenter notes: Now lets look at complications. If we prescribe less do we see more complications? The short answer, perhaps, but hardly any. In a practice of 7000 patients, a 10% reduction in antibiotic prescribing for RTI may result in 1 additional pneumonia each year and 1 additional peritonsilar abscess every 10 years. This study stratified practices by their antibiotic prescribing rates into four quartiles. (>185, , and less than 115 antibiotic prescriptions per 1000 patients. They then looked at infection related complications – pneumonia, peritonsillar abscess, mastoiditis, empyema, meningitis and intracranial abscess. There was no significant reduction in peritonsilar abscess, mastoiditis, empyema, or intracranial abscess, in practices where antibiotics were given much more often, as you can see the confidence intervals cross one and the p values are over Although the slight increase in peritonsilar abscess they suggested would result in one additional peritonsilar abscess every 10 years. There was a significant reduction in pneumonia, indicating that this equated to one additional pneumonia per year. This indicates that we need to be careful in this area – and consider the age and risk of patients with suspected pneumonia, and consider using CRP too. BMJ 2016 Gulliford TARGET Antibiotics Presentation - Main

13 Antibiotics and complications09/12/2017 Antibiotics and complications Serious complications rare after URTI Sore throat and otitis media NNT>4000 Pneumonia more common after LRTI Age >65 years: NNT 39 Age < 65 years: NNT >100 Highlighted in PHE quick reference guide Acute cough & bronchitis NICE RTIs Antibiotics have little benefit if no co-morbidity. Consider a 7-day delayed antibiotic with advice. Symptom resolution can take 3 weeks. Consider immediate antibiotics if >80 years of age and one of: hospitalisation in past year; taking oral steroids; insulin-dependent diabetic; congestive heart failure; serious neurological disorder/stroke, or >65 years with two of the above. Consider CRP if antibiotic is being considered. No antibiotics if CRP<20mg/L and symptoms for >24 hours; delayed antibiotics if mg/L; immediate antibiotics if >100mg/L. Amoxicillin Penicillin allergy: doxycycline 500mg TDS 200mg stat then 100mg OD 5 days Presenter notes: Serious complications are rare after URTI, sore throats and otitis media. There are some patient groups at slightly higher risk of complications after LRTI or bronchitis and the current guidelines target prescribing for those at highest risk, for example in those aged 65 or older with 2 or more of: recent hospitalisation, diabetes, CCF or recent steroid use. and even then you still have to treat a number of patients for one to benefit. TARGET Antibiotics Presentation - Main

14 Reducing complication risk09/12/2017 Reducing complication risk Empowering clinicians to give Careful clinical assessment, including targeting treatment to those most at risk (clinical tools) Back-up / delayed antibiotics Safety netting including patient information leaflets Presenter notes: So most of the really large systematic reviews show that complications are rare. With careful clinical assessment to rule out more serious illness such as pneumonia or sepsis and the use of clinical tools, we can target treatment to those most at risk of complications. We have already discussed identifying those at greater risk of pneumonia. The FeverPAIN tool (see sore throat case study) is another example of clinical tools that help to target care. If we are unsure what to do or for patients who really want antibiotics we can use delayed or back up prescriptions. The PRISM trial shows that a back up prescriptions for sore throat helps to reduce complication rates. We need to provide clear advice around duration of illness and what symptoms or signs may mean that urgent care is needed. These can be reinforced by using patient information leaflets available on the TARGET toolkit, and we will show these later. TARGET Antibiotics Presentation - Main

15 The TARGET Antibiotics Toolkit9 December, 2017 TARGET stands for: Treat Antibiotics Responsibly, Guidance, Education, Tools TARGET aims to help clinicians and commissioners to use antibiotics responsibly and meet CQC requirements Resources include:- Leaflets to share with patients Clinical waiting areas posters and videos Audit tools Self-assessment checklist Training; webinars and e-Modules Antibiotic prescribing data TARGET presentations Presenter notes: So what is the TARGET Antibiotics Toolkit? TARGET stands for Treat Antibiotics Responsibly, Guidance, Education, Tools. The TARGET Antibiotics Toolkit is free on the RCGP website (and easy to find if you Google TARGET antibiotics). TARGET aims to influence prescribers’ and patients’ intentions to prescribe antibiotics by influencing their personal attitudes, social norms and perceived barriers to optimal antibiotic prescribing, and then facilitates this with action planning within the workshop. This is the landing page of the TARGET antibiotics website. The tools available on the website will help you to prescribe antibiotics responsibly and assist in the ensuring some of the Care Quality Commission regulations are met. The website has links to pages containing: Training resources for group or personnel continuing professional development around infections and antibiotic use. Patient information leaflets. A self-assessment check list like the one you just completed. Resources for clinicians to use in their waiting rooms. The PHE antibiotic and diagnostic guides. Other external links to other useful resources around antibiotic use. There is also a hard copy Guide to Resources. We will now go through some clinical scenarios, some evidence behind what can influence prescribing, and how the TARGET resources can be used to support you and your colleagues to use antibiotics even better than you are now. TARGET Antibiotics Presentation - Main

16 Clinical scenario 2: Acute cough9 December, 2017 Clinical Scenario Acute Cough Presenter notes: These cases are examples that can be printed out and discussed in pairs or groups, or with the group as a whole. Allow the participants to discuss the case for 2 minutes and specifically ask several different people what they would do and /or prescribe. TARGET Antibiotics Presentation - Main

17 Clinical scenario: Acute cough9 December, 2017 Clinical Scenario Acute Cough Please consider the following details:- 45 year old smoker with cough 1/52, green sputum Temp 37.8°C Has had several previous episodes of bronchitis and insists antibiotics ‘always help’ PEFR normal Scattered course creps and wheeze, vesicular breath sounds, no focal crepitation's Presenter notes: These cases are examples that can be printed out and discussed in pairs or groups, or with the group as a whole. Allow the participants to discuss the case for 2 minutes and specifically ask several different people what they would do and /or prescribe. It may be useful to also change the scenario slightly- how would this change if the patient was 81 years old and had been in hospital 6 months previously. TARGET Antibiotics Presentation - Main

18 Clinical scenario acute cough: PHE Antibiotic Management Guidance9 December, 2017 Clinical Scenario Acute Cough ILLNESS GOOD PRACTICE POINTS DRUG ADULT DOSE/ DURATION Acute cough & bronchitis NICE RTIs Antibiotics have little benefit if no co-morbidity. Consider a 7-day delayed antibiotic with advice. Symptom resolution can take 3 weeks. Consider immediate antibiotics if >80 years of age and one of: hospitalisation in past year; taking oral steroids; insulin-dependent diabetic; congestive heart failure; serious neurological disorder/stroke, or >65 years with two of the above. Consider CRP if antibiotic is being considered. No antibiotics if CRP<20mg/L and symptoms for >24 hours; delayed antibiotics if mg/L; immediate antibiotics if >100mg/L. Amoxicillin Penicillin allergy: doxycycline 500mg TDS 200mg stat then 100mg OD 5 d Presenter notes: We suggest you take your local guidance with you The TARGET website also has the national antibiotic guidance, which is used by most CCGs to develop their local guidance. This is a snapshot of the aims and principles of treatment section of the Management of Infection Guidance for acute cough. As you can see each section has links to other guidance, comments on when antibiotics should be used, recommended first and second line antibiotics dose and duration. For acute cough, we suggest that antibiotics have little benefit if no co-morbidity. We recommend amoxicillin first line; co-amoxiclav is not recommended second line, rather PHE recommends doxycycline second line. This PHE guidance on the TARGET website, also has an extensive rationale section which is really useful for trainers and trainees, or just when you want a bit more information for yourself or the patient. Presenter please tell the participants where to find your local guidance and how locums can get extra copies if needed. Rationale behind recommendations 1. NICE Clinical Guideline 69. Respiratory Tract Infections - antibiotic prescribing for self-limiting respiratory tract infections in adults and children in primary care. July RATIONALE: Describes strategies for limiting antibiotic prescribing in self-limiting infections and advises in which circumstances antibiotics should be considered. A no antibiotic or a delayed antibiotic prescribing strategy should be agreed for patients with acute cough/chronic bronchitis. In the 2 RCTs included in the review, the delay was 7-14 days from symptom onset and antibiotic therapy. Patients should be advised that resolution of symptoms can take up to 3 weeks and that antibiotic therapy will make little difference to their symptoms and may result in side effects. Patients should also be advised to seek a clinical review if condition worsens or becomes prolonged. The evidence behind these statements is primarily from the studies referred to below. There has been no systematic review of the evidence of length of antibiotic treatment for acute cough or bronchitis when antibiotics are prescribed. However the NICE pneumonia guidance group found evidence for the efficacy of 5 days’ antibiotic to treat pneumonia; therefore it is reasonable to consider that 5 days would also be effective in bronchitis. 2. Fahey T, Smucny J, Becker L, Glazier R. Antibiotics for acute bronchitis. In: The Cochrane Library, 2006, Issue 4. Chichester, UK: John Wiley & Sons, Ltd Accessed RATIONALE: Systematic review of nine studies (4 in primary care). Studies in primary care showed antibiotics reduced symptoms of cough and feeling ill by less than one day in an illness lasting several weeks in total. 3. Chronic cough due to acute bronchitis. Chest. 2006;129:95S-103S. RATIONALE: Clinical guidelines on managing cough associated with acute bronchitis. Large body of evidence including meta-analyses and systematic reviews does not support routine antibiotic use. 4. Wark P. Bronchitis (acute). In: Clinical Evidence. London. BMJ Publishing Group. 2008;07: RATIONALE: Discusses the evidence to support self care and limiting antibiotic prescriptions. Systematic review of 13 RCTs found that antibiotics only modestly improved outcomes compared with placebo. 5. Francis N et al. Effect of using an interactive booklet about childhood respiratory tract infections in primary care consultations on reconsulting and antibiotic prescribing: a cluster randomised controlled trial. BMJ 2009;339:2885. RATIONALE: Utilising an information booklet during primary care consultations for children with RTIs significantly decreased antibiotic use (absolute risk reduction 21.3% (95%CI, p<0.001). Reconsultation occurred in 12.9% of children in intervention group and 16.2% in control group (absolute risk reduction 3.3%, no statistical difference). There was no detriment noted to patient satisfaction in the intervention group. 6. Treatment of acute bronchitis available in Clinical Knowledge Summaries website: Accessed Acute exacerbation of COPD 1. Anthonisen MD, Manfreda J, Warren CPW, Hershfield ES, Harding GKM, Nelson NA. Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease. Ann Int Med 1987;106: RATIONALE: Describes the cardinal signs of an infective exacerbation of COPD and the evidence for commencing antibiotics. Randomised double blinded cross-over trial showed a significant benefit from using antibiotics. Success rate with antibiotic therapy 68% vs 55% with placebo. 2. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for Diagnosis, Management, and Prevention of COPD. Management of exacerbations. Updated December Discusses the aetiology, pathophysiology and evidence based therapeutic management of COPD. Antibiotic therapy is stratified according to severity of disease. S. pneumoniae, H. influenzae, M. catarrhalis remain the predominant pathogens in mild disease. 3. Chronic obstructive pulmonary disease. Management of COPD in adults in primary and secondary care. NICE Clinical Guideline 12 February Accessed RATIONALE: A meta-analysis of nine trials found a small but statistically significant effect favouring antibiotics over placebo in patients with exacerbations of COPD. Effect size 0.22 (95% CI, 0.1 to 0.34). Four studies assessed whether there was a relationship between severity of exacerbation and the effectiveness of antibiotic use. Three of these studies suggest that the worse the COPD severity of exacerbation (lung function impairment (FEV1, PEFR), purulence of sputum) then the greater the degree of benefit from antibiotics. 4. El Moussaoui R, Roede BM, Speelman P, Bresser P, Prins JM, Bossuyt PMM. Short-course antibiotic treatment in acute exacerbations of chronic bronchitis and COPD: a meta-analysis of double-blind studies. Thorax 2008;63: RATIONALE: In this meta-analysis they concluded that a short course of antibiotic treatment was as effective as the traditional longer treatment in patients with mild to moderate exacerbations of chronic bronchitis and COPD. The meta-analysis included 21 double-blind randomised clinical trials with 10,698 adults with exacerbation of COPD or chronic bronchitis, no antimicrobial therapy at the time of diagnosis and random assignment to antibiotic treatment for less than or equal to 5 days versus more than 5 days. At early follow-up (<25 days), the summary odds ratio (OR) for clinical cure with short treatment versus conventional treatment was 0.99 (95% CI 0.90 to 1.08). At late follow-up the summary OR was 1.0 (95% CI 0.91 to No trials of amoxicillin or doxycycline were included in the meta-analysis; however there is no microbiological reason that a 5 day course of these agents would be inferior to a 5 day course of clarithromycin in acute exacerbations of COPD. Available via PHE or RCGP websites with full rationale & references TARGET Antibiotics Presentation - Main

19 Clinical scenario acute cough: Feedback9 December, 2017 Clinical Scenario Acute Cough 45 year old smoker with cough 1/52, green sputum Temp 37.8°C Has had several previous episodes of bronchitis and insists antibiotics ‘always help’ PEFR normal Scattered course creps and wheeze, vesicular breath sounds, no focal crepitation’s Antibiotic little benefit as no co-morbidity Consider no, or 7d back up antibiotic with safety netting Share a leaflet with the patient – e.g. TARGET RTI leaflet Advise patient symptom resolution can take 3 weeks Presenter notes: These cases are examples that can be printed out and discussed in pairs or groups, or with the group as a whole. In this case a no, or back-up antibiotic prescription (7 day) strategy with safety netting advice using a patient leaflet (see TARGET) could be used as the symptoms do not suggest immediate antibiotic use is required. But the clinician needs to assess how ”ill” he considers the patient is. NICE Clinical Guideline 69. Respiratory Tract Infections - antibiotic prescribing for self-limiting respiratory tract infections in adults and children in primary care. July The NICE guidance suggests a no antibiotic or a delayed antibiotic prescribing strategy should be agreed for patients with acute cough/chronic bronchitis. In the 2 RCTs included in the review, the delay was 7-14 days from symptom onset and antibiotic therapy. Patients should be advised that resolution of symptoms can take up to 3 weeks and that antibiotic therapy will make little difference to their symptoms and may result in side effects. Patients should also be advised to seek a clinical review if condition worsens or becomes prolonged. In a European study of 3,000 primary care patients with acute cough across 13 countries, clinical outcome was similar whether antibiotics were given or not (Butler et al BMJ:339 b 2242). In an RCT of amoxicillin 1g tds vs placebo in 2061 patients 18yrs and over with acute LRTI when pneumonia was not suspected. New or worsening symptoms were significantly less common in amoxicillin (15.9%) than in the placebo group 19.3% (NNT30). Nausea, rash or diarrhoea were significantly more common in the amoxicillin group (number needed to harm 21). There was no increased benefit in those over 60 yrs (Little et al, Lancet Infect Dis 2013:123-9). In this same patient series those with a history of significant co-morbidities experienced a significantly greater reduction in symptom severity between days 2 & 4. Those with a short prior illness <7days, or non smokers antibiotics provided a modest benefit. (Br J Gen Pract 2014). TARGET Antibiotics Presentation - Main

20 9 December, 2017 Prescribing: 50% of total are amoxicillin Your Data October 2015 – September 2016 Clinical Scenario Acute Cough Total antibacterial Items/STAR-PU Vs Co-amoxiclav, Cephalosporin and Quinolone % Items Presenter notes:– Antibiotic prescribing data is available from the NHS England Antibiotic Quality Premium monitoring dashboard here: Or data is available from FingerTips: https://fingertips.phe.org.uk/ This is free to access on the NHS England web site and will be updated at the start of each month. You should be able to access prescribing data for your CCG and insert it onto this slide. This scatter plot shows the variation in total number of antibiotic items on the vertical Y axis, and the % of the total that the co-amoxiclav, cephalosporin and quinolone items make up, on the horizontal X axis. As you can see there is a wide variation in use in total items across England, but also here locally in this CCG (seen in the darker dots). There is an even greater variation in the use of co-amoxiclav, cephalosporins and quinolones. This dot represents where you fall in the distribution compared to others in this CCG and nationally. You are … [describe location on the chart] The variation suggests that there is an opportunity for you to decrease your prescribing. Even if you are very low and can rightly feel proud about your practice prescribing – we still prescribe almost double that in the Netherlands. TARGET Antibiotics Presentation - Main

21 Hawker et al J AC 2014; Ashworth et al BJGP 2005.9 December, 2017 Prescribing: Consultations, and amoxicillin prescribing for acute cough & cold has increased Clinical Scenario Acute Cough 537 UK GP practices Presenter notes: So why despite our discussions that we don’t usually prescribe for uncomplicated cases is prescribing increasing as shown in this graph? Think about your own prescribing – how often do you use amoxicillin for coughs? This data from general practices in England and Wales from the RCGP GP Research network shows that consultations for coughs and colds has increased since 2000, and the antibiotic prescribing has increased with it. The proportion of cough/cold episodes for which antibiotics were prescribed decreased from 47% in 1995 to 36% in 1999, before increasing to 51% in But there was marked variation in the percentage of patients in each practice that were prescribed antibiotics, in 2011 the 10th to 90th percentile range was 32%–65%. This variation was NOT influenced by age or social group. Variation in prescribing by practices persists. This study also looked at other infections: the proportion of GP consultations in which patients were prescribed antibiotics for sore throat was 62% in 2011 – but again with a wide range 10th to 90th percentile range of 45%–78%. There was a similar very wide range for the % of patients prescribed antibiotics who had a consultation for otitis media 63%–97% and all upper respiratory tract infections from 33%–74%. This suggests that all of us could probably reduce our antibiotic prescribing – but those at the higher end of the range could do so more than others. Think about your own prescribing – do you think you are at the upper end? If yes you may wish to consider CRP more actively CLICK TO BRING IN: In another longitudinal study Ashworth et al showed that practices that reduced their antibiotic prescribing also reduced their consultations for RTI, suggesting that patients can be retrained not to expect antibiotics and as a result consult less. So reducing your workload – or at least allowing you to concentrate on other things! Extra presenter notes from reference: Hawker et al. J Antimicrob Chemother. 2014: doi: /jac/dku291. Trends in antibiotic prescribing in primary care for clinical syndromes subject to national recommendations to reduce antibiotic resistance, UK 1995–2011: analysis of a large database of primary care consultations. This study measured trends in antibiotic prescribing in UK primary care in relation to nationally recommended best practice. Patients and methods: A descriptive study linking individual patient data on diagnosis and prescription in a large primary care database, covering 537 UK general practices during 1995–2011. Results: The proportion of cough/cold episodes for which antibiotics were prescribed decreased from 47% in 1995 to 36% in 1999, before increasing to 51% in There was marked variation by primary care practice in 2011 [10th–90th percentile range (TNPR) 32%–65%]. Antibiotic prescribing for sore throats fell from 77% in 1995 to 62% in 1999 and then stayed broadly stable (TNPR 45%–78%). Where antibiotics were prescribed for sore throat, recommended antibiotics were used in 69% of cases in 2011 (64% in 1995). The use of recommended short-course trimethoprim for urinary tract infection (UTI) in women aged 16–74 years increased from 8% in 1995 to 50% in 2011; however, a quarter of practices prescribed short courses in≤16% of episodes in 2011. For otitis media, 85% of prescriptions were for recommended antibiotics in 2011, increasing from 77% in All these changes in annual prescribing were highly statistically significant (P,0.001). Conclusions: The implementation of national guidelines in UK primary care has had mixed success, with prescribing for coughs/colds, both in total and as a proportion of consultations, now being greater than before recommendations were made to reduce it. Extensive variation by practice suggests that there is significant scope to improve prescribing, particularly for coughs/colds and for UTIs. Ashworth et al BJGP Variations in antibiotic prescribing and consultation rates for acute respiratory infection in UK general practices 1995–2000. analysed data from the General Practice Research Database, including all registered patients from 108 practices between 1995 and For each practice, numbers of consultations for acute respiratory tract infections and the proportion of consultations resulting in an antibiotic prescription were obtained. An age- and sex-standardised consultation ratio (SCR) and standardised prescription ratio (SPR) were calculated for each practice. We evaluated whether SPR and SCR values were associated. The results showed that for the mid-year data (1997), the crude consultation rate for all acute respiratory infections ranged from 125–1110 per 1000 registered patients at different practices; the proportion of consultations with antibiotics prescribed ranged from 45–98%. After standardising for varying age and sex structure of practice populations, practices with lower SPR values had lower SCR values (r = 0.41; P<0.001). This association was observed in each study year. Moreover, practices that demonstrated reductions in SPR between 1995 and 2000 also showed reductions in SCR (r = 0.27; P = 0.005). Consultation rates related to prescribing In a longitudinal study, practices who reduced prescribing experienced a reduced consultation rate Thus patients can be retrained not to expect antibiotics reducing your consultations Hawker et al J AC 2014; Ashworth et al BJGP 2005. TARGET Antibiotics Presentation - Main

22 The Patient Perspective: What do patients do when they have an RTI?9 December, 2017 Clinical Scenario Acute Cough 1,707 ≥16y in England Jan 2017 959, 56% throat, ear, sinus, chest infection or cough, flu 33% carried on most of their usual daily activities/ routine 23% took extra rest 34% took OTC medicine for symptoms 18% used alternative medicine (honey, herbal) for symptoms 5% Got advice from friend/family colleague 11% asked pharmacy for advice (6% in 2011) 22% Contacted or visited GP surgery 3% visited NHS walk in, 3% GP OOH, 2% Hosp A&E 3% used NHS choices, 1% telephoned NHS 111 0.4% took left-over antibiotics Presenter notes: Do patients expect antibiotics for RTIs? In a 2017 face to face survey in randomly selected homes, 56% of 1707 participants reported having an RTI in the past 12 months. We asked the 969 (74%) participants reporting cough, throat, ear, sinus, chest infection or flu symptoms in the last year VQ03 - Thinking of your MOST RECENT illness which of the following actions, if any, did you take as a result? A third reported that they carried on most of their usual activities or work (33% with no variation with age, but significantly higher in social grade AB, or higher education)), or took non-prescription medications available over the counter (34% ). One fifth (18%, women 21% vs men 14%) took other honey or herbal remedies, or took extra rest (23%, under 34 years more likely and if single or no children). Less than one-in-twenty sought advice from friends, colleagues or family, although this was significantly higher in younger participants years (12%). Use of websites for advice was very low, with only 3% seeking advice from websites One-tenth asked for advice at their pharmacy, while one-fifth (22%) contacted their local doctor’s surgery. Those who worked part-time (18%) were significantly more likely to have asked for advice at a pharmacy. Those with no educational qualifications versus those with any qualifications, and those over 65 years than those under 25 years, were significantly more likely to contact their GP or (no formal qualification 35% p<0.05 compared to all other groups; over 64 years 28% vs under 25 years 17%, p<0.05). If they had used a face to face health care service all were most likely to have last visited their doctors surgery (79%) but this was significantly lower in the younger age groups compared to those over 55 years (65% 15-24y, 71% y VS 94% 55-64y, 90% 65Y+ p<0.05 ). Younger patients were more likely to have visited an NHS walk in centre and said this was their last visit (21% 15-24y vs 0-1% over 55years). Younger participants year olds were significantly more likely to have used the NHS choices website (8%), visited an NHS walk in centre (6%) which is significantly higher than all other age groups except year olds (5%) or contacted NHS 111 (3%), than most other age groups McNulty, Lecky, Butler. Ipsos MORI survey January 2017 TARGET Antibiotics Presentation - Main

23 McNulty, Lecky, Butler. Ipsos MORI survey January 2017The Patient Perspective 2017 n=249 Why they visited GP with RTI (not cold/runny nose) 30% Needed treatment to help symptoms 24% Symptoms severe (breathing 11%, sleep 14%) 26% Symptoms lasted longer than I expected 15% Worried illness could get worse 11% Wanted to know the cause 9% I usually go to doctor’s surgery with these symptoms 8% I already have another health condition Clinical Scenario Acute Cough What did they expect? 38% Expected antibiotics 18% Advice on need for antibiotics 34% Other treatment for symptoms 17% To find out cause 25% Advice about self-care 13% Rule out more serious illness Information about illness duration 4% For referral to hospital/specialist McNulty, Lecky, Butler. Ipsos MORI survey January 2017

24 The Patient Perspective: A 2017 survey showed patients trust GPs’ and nurses’ advice9 December, 2017 Clinical Scenario Acute Cough Presenter notes: We know patients trust GP’s, nurses and pharmacists to give them advice. 85% of participants in a 2017 survey of 1691 randomly selected members of the English public reported that they trusted their GP’s advice as to whether they needed antibiotics or not; 72% trusted their nurse and 71% trusted their pharmacist. So there is a great opportunity for clinicians and pharmacists to share information with patients about the need or not for antibiotics. Extra presenter notes: The 2017 survey also showed that 57% of of participants who had taken antibiotics or had an infection in the last year (received some information about the illness or antibiotics. Most participants were given information verbally (83%), in the GP surgery (65%). One-fifth (21%) were given the information in a printed format, and the professional went through or discussed the printed information with them in 42%. One in eight (14%) were given information at a pharmacy;–One-fifth how to take antibiotics but far fewer about other things related to antibiotics. About One –tenth  recalled being given some advice about the symptoms. so there is an opportunity to give more printed information about antibiotics and sef-care. This survey is also supported by another recent large Eurobarometer survey showing that 90% of the UK public would use their GP as a trustworthy source of antibiotic information. It’s worth sharing information about the need or not for antibiotics in consultations, and self care McNulty et al. Ipsos Mori 2017; Base: All respondents (1,691); Fieldwork: 24th Jan–5thFeb 2017 TARGET Antibiotics Presentation - Main

25 What is the evidence for back-up / delayed prescribing?9 December, 2017 Clinical Scenario Acute Cough English RCT comparing three treatment strategies for sore throat (n=582) Presenter notes: There has been much discussion about the use of giving delayed antibiotic prescriptions in acute uncomplicated infections, to reduce antibiotic use and reduce patient expectations (although patients understand the term back-up more easily – so we have now changed to this term. A Cochrane review has recently shown the benefits of this approach, without increasing complications in patients. This study in acute sore throat is an exampler. patients in 11 English GP practices were randomised into immediate antibiotics, delayed antibiotics and no antibiotics groups. There was no difference in recovery rates and high levels of satisfaction with all strategies. Compared to immediate antibiotics those given no antibiotics or delayed antibiotics had a reduction in belief in antibiotics for sore throat and were less likely to visit the GP again for similar symptoms. A more recent study of acute sore throat (the DESCARTE study) in fact showed that complications in those who received immediate were similar to those receiving a back-up prescription even though 30% did not collect the prescription, and were higher in the no antibiotic group. The back-up prescription is very useful to give to patients who have a high expectation for antibiotics, and can be given using the patient leaflet I will show you. Detailed results of Little et al: Median duration of antibiotic use differed significantly in the three groups (10 v 0 v 0 days, P < 0.001); 69% of patients in group 3 did not use their prescription. The proportion of patients better by day 3 did not differ significantly (37% v 35% v 30%, P = 0.28), nor did the duration of illness (median 4 v 5 v 5 days, P = 0.39), days off work or school (median 2 v 2 v 1, P = 0.13), or proportion of patients satisfied (96% v 90% v 93%, P = 0.09), although group 1 had fewer days of fever (median 1 v 2 v 2 days, P = 0.04). More patients in group 1 thought the antibiotics were effective (87% v 55% v 60%, P < 0.001) and intended coming to the doctor in future attacks (79% v 54% v 57%, P < 0.001). "Legitimation" of illness-to explain to work or school (60%) or family or friends (37%)-was an important reason for consultation. Patients who were more satisfied got better more quickly, and satisfaction related strongly to how well the doctor dealt with patient's concerns. In other studies delayed prescribing has led to the greatest reduction in future consultation in sore throat (Little 2007) and LRTI (Moore 2009). A Cochrane review of 10 studies has shown that delayed prescribing reduces antibiotic prescriptions without reducing satisfaction Antibiotic use (%) Satisfaction (%) Immediate 93 92 Delayed 32 87 No 14 83 Little, Williamson, Warner et al. BMJ . (1997) 314: DRAFT TARGET antibiotics presentation clinical scenario based -SG CMCN amendments

26 The Patient Perspective: Back-up/delayed Prescribing: What patients do9 December, 2017 Clinical Scenario Acute Cough Women compared with men (6% vs 4%) Presenter notes: This survey of the public showed that 5% of 3,385 members of the general public in 2017 reported being given a Back-up /delayed antibiotic prescription, so the strategy is being used a little by GPs. Click to bring in 42% reported not taking the antibiotic Of those 165 participants reporting being given a delayed/back-up antibiotic prescription, 57% reported starting to take it and 42% said they did not. (The sample size is too small to say any more about this group offered delayed antibiotics. ) When asked to score the acceptability of being given a delayed/back-up antibiotic out of 10 (where 1 completely unacceptable and 10 completely acceptable) the mean score was 8.5, with 59% scoring completely acceptable, and only 5 (3%) respondents scored 1. The commonest indication for a delayed/back-up antibiotic, as in 2014, was for chest infection, but urine infection now constitutes 16% (7% in 2014). So what is the Implication? With the continued low use, and lack of understanding of what it is by the general public and more than a quarter opposing the practice – more education and explanation will be needed, but the suggestion of great variation by area suggests that local activity may be having an affect Further notes for presenter: - other questions were asked about delayed antibiotics One-fifth of the general public (21%) know something about delayed /back-up antibiotic prescriptions s; and 14% of them fully aware, with a further 7% knowing the name or something about the practice. Women, those with children and those in social grades AB were more informed. This understanding is surprisingly slightly lower than in But interestingly, The North (30%) and south West (18%) were significantly more likely to be fully aware than all other areas – It would be interesting to speculate why this is – there has been a lot of AMS activity in the Northern area through the North of England Commissioning Support (NECS) using the TARGET leaflet, whereas North West and London have less activity. The RCTs of delayed prescribing have been undertaken in several areas within the South West, but not all. Support for delayed/backup antibiotic prescribing. Interestingly although there were slightly less fully aware of the term in 2017, than in 2014,  slightly more were supportive of the practice for throat, ear or urine infections, With a few percent more being strongly or tending to favour the practice, and a few percent less being strongly opposed. Women compared with men, those with children, and younger (under 35 years) compared with older (over 55 Years) more likely to support. There is no difference by social grade. Not surprisingly if they knew something about the practice of delayed/back –up prescribing they were more likely to support it (fully 54% for throat), than those who were not aware of the practice (37%). The North were significantly more likely to strongly support delayed prescribing for infections, but the differences were not as great as for awareness 42% reported not taking the antibiotic Acceptability score 1-10 Mean score 8.5 McNulty et al. Ipsos Mori 2017; Base: All respondents (3,385); Fieldwork: 24th Jan -12thFeb 2017 DRAFT TARGET antibiotics presentation clinical scenario based -SG CMCN amendments

27 A meta analysis of English Primary CareEvidence: Risk of resistance persists for at least 12 months after your prescribing 9 December, 2017 Clinical Scenario Acute Cough Increased risk of resistant organism Antibiotic in past 2 months Antibiotic in past 12 months RTI 7 studies: n = 2,605 2.4 times Presenter notes: Lets take a moment to reflect. What do you think about antibiotic resistance? Is it important in your practice? (Pause for feedback) Does your own antibiotic prescribing influence antibiotic resistance in your patients or community? (pause for feedback) Resistance is now with us in primary care and The risk of resistance is even greater in the first two months after an antibiotic as shown here for Respiratory Tract infections, but is still higher 12 months after antibiotic use for RTIs. Individuals prescribed an antibiotic in primary care for a respiratory infection have an increased risk of subsequently carrying resistant organisms – so that the next time they have an infection it may be with one of these antibiotic resistant organism. So in conclusion, any antibiotic use increases our future risk of carrying resistant bacteria, even if it is amoxicillin, as this resistance gene is often linked to others like trimethoprim. Details of paper: The review included 24 studies; 22 involved patients with symptomatic infection and two involved healthy volunteers; 19 were observational studies (of which two were prospective) and five were randomised trials. In five studies of urinary tract bacteria (14 348 participants), the pooled odds ratio (OR) for resistance was 2.5 (95% confidence interval 2.1 to 2.9) within 2 months of antibiotic treatment and 1.33 (1.2 to 1.5) within 12 months. In seven studies of respiratory tract bacteria (2605 participants), pooled ORs were 2.4 (1.4 to 3.9) and 2.4 (1.3 to 4.5) for the same periods, respectively. Studies reporting the quantity of antibiotic prescribed found that longer duration and multiple courses were associated with higher rates of resistance. Studies comparing the potential for different antibiotics to induce resistance showed no consistent effects. Only one prospective study reported changes in resistance over a long period; pooled ORs fell from 12.2 (6.8 to 22.1) at 1 week to 6.1 (2.8 to 13.4) at 1 month, 3.6 (2.2 to 6.0) at 2 months, and 2.2 (1.3 to 3.6) at 6 months. Therefore in conclusion, individuals prescribed an antibiotic in primary care for a respiratory infection have an increased risk of carrying resistant organisms – so that the next time they have an infection it is with a antibiotic resistant organism. The effect is greatest in the month immediately after treatment but may persist for up to 12 months. This effect not only increases the population carriage of organisms resistant to first line antibiotics, but also creates the conditions for increased use of second line antibiotics in the community. A meta analysis of English Primary Care Costello et al. BMJ. (2010) 340:c2096. TARGET Antibiotics Presentation - Main

28 Cals et al, BMJ 2009;338:1374, NICE clinical guideline 1919 December 2017 Evidence for CRP and communication in acute cough in general practice Clinical Scenario Acute Cough Care for LRTI Antibiotics prescribed Usual care 68% Communication skills and leaflet 33% CRP to aid diagnosis 39% Both CRP & communication 23% I M P A C3 T NICE: Patients with LRTI symptoms if diagnosis of pneumonia has not been made and it is not clear whether antibiotics are needed C-reactive protein mg/litre Management Less than 20 Do NOT routinely offer antibiotics Consider delayed antibiotic prescription Greater than 100 Offer immediate antibiotics The IMPACT study in the Netherlands showed that use of communication skills with GPs in which they shared information with patients halved antibiotic use. This supports the use of shared information. CRP alone was also very effective and the combination of both decreased antibiotic use the most. Click to bring in information about NICE: Thus NICE guidance now suggests that: For people presenting with symptoms of lower respiratory tract infection in primary care, consider a point of care C-reactive protein test if after clinical assessment a diagnosis of pneumonia has not been made and it is not clear whether antibiotics should be prescribed. Use the results of the C-reactive protein test to guide antibiotic prescribing in people without a clinical diagnosis of pneumonia as follows: Do not routinely offer antibiotic therapy if the C-reactive protein concentration is less than 20mg/litre. Consider a delayed antibiotic prescription (a prescription for use at a later date if symptoms worsen) if the C-reactive protein concentration is between 20mg/litre and 100mg/litre. Offer antibiotic therapy if the C-reactive protein concentration is greater than 100mg/litre. NICE clinical guideline 191. Diagnosis and management of community- and hospital-acquired pneumonia in adults. Issued: December https://www.nice.org.uk/guidance/cg191 Accessed Reference for the IMPACT study: Effect of point of care testing for C reactive protein and training in communication skills on antibiotic use in lower respiratory tract infections: cluster randomised trial. Jochen W L Cals, Christopher C Butler, Rogier M Hopstaken, Kerenza Hood, Geert-Jan Dinant. BMJ 2009;338:b1374 doi: /bmj.b1374. Objective To assess the effect of general practitioner testing for C reactive protein (disease approach) and receiving training in enhanced communication skills (illness approach) on antibiotic prescribing for lower respiratory tract infection. Design: Pragmatic, 2×2 factorial, cluster randomised controlled trial. Setting: 20 general practices in the Netherlands. Participants: 40 general practitioners from 20 practices recruited 431 patients with lower respiratory tract infection. Main outcome measures: The primary outcome was antibiotic prescribing at the index consultation. Secondary outcomes were antibiotic prescribing during 28 days’ follow-up, reconsultation, clinical recovery, and patients’ satisfaction and enablement. Interventions: General practitioners’ use of C reactive protein point of care testing and training in enhanced communication skills separately and combined, and usual care. Results: General practitioners in the C reactive protein test group prescribed antibiotics to 31% of patients compared with 53% in the no test group (P=0.02). General practitioners trained in enhanced communication skills prescribed antibiotics to 27% of patients compared with 54% in the no training group (P<0.01). Both interventions showed a statistically significant effect on antibiotic prescribing at any point during the 28 days’ follow-up. Clinicians in the combined intervention group prescribed antibiotics to 23% of patients (interaction term was nonsignificant). Patients’ recovery and satisfaction were similar in all study groups. Conclusion Both general practitioners’ use of point of care testing for C reactive protein and training in enhanced communication skills significantly reduced antibiotic prescribing for lower respiratory tract infection without compromising patients’ recovery and satisfaction with care. A combination of the illness and disease focused approaches may be necessary to achieve the greatest reduction in antibiotic prescribing for this common condition in primary care. Trial registration Current Controlled Trials ISRCTN Cals et al, BMJ 2009;338:1374, NICE clinical guideline 191 TARGET Antibiotics Presentation - Main

29 TARGET antibiotics presentation 18.09.14TARGET: Patient Information Leaflets Treating Your Infection RTI Leaflet 9 December, 2017 Treating your infection RTI leaflet Clinical Scenario Acute Cough All sections can be personalised and added to by the GP “Most get better by” section educates patients about when to consult Safety netting Extra presenter notes: It would be useful to print off a copies of this leaflet and take enough with you for each GP. They can be found at The treating your infection leaflet has been developed through extensive feedback with patients and clinicians over the last 2 years. It is designed to be shared with the patient and completed with them during the consultation. Its aim is to increase the patients confidence to self-care, and to facilitate the use of back-up antibiotic, but it also allows the patients to go away with something, so ending the consultation on a positive note. Bring in personalised text box All sections can be personalised and added to by the GP. And it is important to share it with the patient and add extra infections , self-care instructions in the third column and alarm symptoms in the fourth column that may be required. Bring in ‘most get better by’ text box The ‘usually lasts’ section allows patients to understand not only for this consultation but also others when they should consult. This section has consistently been seen as very useful by patients of all ages. Bring in safety netting box Whatever the infection, in this era of antibiotic resistance and with increasing numbers of elderly or vulnerable patients, it is extremely important to give some clear safety netting instructions. These are some that can be used and saved by patients. Bring in back-up prescription box The back-up prescription can reduce antibiotic prescribing by about 30 to 40%, and is extremely useful for particularly demanding patients or just before a weekend to reduce visits to out of hours services. Bring in information box Although most patients know they shouldn’t take antibiotics for coughs and colds, far fewer know that sinusitis, ear infections and sore throats and many other infections get better on their own without antibiotics. Likewise they know little about antibiotic resistance, so we should take every opportunity to educate them. In % of antibiotics were taken without a prescription, this is a particular problem in patients under 24 years. So take the opportunity to stress not to share antibiotics. There is a READ code for delayed/ back-up antibiotics or leaflet given and if you Read code the infections featured the leaflet with EMIS and some other systems this leaflet will appear on your computer via the patient.co.uk system. Extra notes for presenter: Most prescribers have access to many leaflets, both paper ones and ones that can be printed off their computer system or the web. However, not all information resources are based on the best available evidence or have been developed through rigorous processes. The Antibiotic Information Leaflet has been developed through over 24 months of literature searching, consultation, focus groups with patients and staff, drafting and revision. Overview of the leaflet To use this leaflet properly, it is important that clinicians use it as a tool to interact with patients, rather than just handing it to them as a ‘parting gift’. In order to communicate this effectively you must make sure that you are very familiar with its content. Please make sure that, in addition to completing this training, you take some time to thoroughly familiarise yourself with the leaflet before you start using it. . Back-up prescription Information about antibiotics & resistance Read codes: Delayed:8CAk, Leaflet: 8CE TARGET Antibiotics Presentation - Main

31 TARGET: Resources for clinical and waiting areas9 December, 2017 Clinical Scenario Acute Cough Posters for Display Presenter notes: These posters and videos may make a difference to patient expectations about when to expect antibiotics, IF used in the waiting room where patients can see them and IF they have the time to digest the information. In % of the general public surveyed remembered seeing the first poster and 95% of these correctly answered that antibiotics don’t help most coughs and colds. Used alone without any other strategies posters will make little difference to patients expectations for antibiotics, but they can be used to reduce expectations and can be used as a prompt for dialogue – “you may have seen from the posters or videos in the waiting room that we in this practice encourage responsible antibiotic prescribing” The videos were developed with patients and each animal cartoon video appealed to different people. A recent small survey of their use showed that those patients who saw them remembered the messages – however often the video sound was muted, chairs were pointing in the wrong direction or the video screen was off. If you intend to use them please don’t make this mistake. Videos for patient waiting areas TARGET Antibiotics Presentation - Main

32 What actions can you agree with you team for this year?Acute cough: Reflect on actions your practice can take to improve prescribing 9 December, 2017 Evidence Most patients with acute cough do not require antibiotics reducing antibiotic prescribing can reduce consultations Patients trust you to give reassurance and advice QP demands sustained reduction of total antibiotics in primary care, with items /STAR-PU < 2013/14 mean. Clinical Scenario Acute Cough Presenter notes: Thus Most patients with acute cough do not require antibiotics Reducing antibiotic prescribing can reduce consultations Patients trust you to give reassurance and advice What actions can we agree for this year? Try to get to get participants to suggest some of the things that others have used in their practice – including the things on this list. The next slide details them Use antibiotic guidance so consistent approach in practice – use the local or direct to the PHE one with rationale on the RCGP website, and make sure used by all in the practice Use NO, or back-up antibiotic and safety net – discuss how this could be done in their practice Use the TARGET leaflet: discuss how they use leaflets and if they know about the TARGET leaflet Consider CRP to guide in difficult cases or for clinicians with particularly high antibiotic use Consider and audit of antibiotic use in acute cough using the resource on the RCGP website Complete the free RCGP RTI clinical course What actions can you agree with you team for this year? TARGET Antibiotics Presentation - Main

33 Can we now agree who will take these things forward and whenAcute cough: Reflect on actions your practice can take to improve prescribing 9 December, 2017 Clinical Scenario Acute Cough Ideas from other GP staff and medicine managers All staff use antibiotic guidance so consistent approach Use NO, or back-up antibiotic and safety net Use the TARGET leaflet – and set up on clinical system Consider CRP to guide in difficult cases Consider an audit of antibiotic use in acute cough Complete the free RCGP RTI clinical course (MARTI) Put up antibiotic posters and use as hook in consultation Presenter notes: Thus Most patients with acute cough do not require antibiotics Reducing antibiotic prescribing can reduce consultations Patients trust you to give reassurance and advice What actions can we agree for this year? Try to get to get participants to suggest some of the things that others have used in their practice – including the things on this list, and get them to agree who should be responsible to take the action forward and by when. Use antibiotic guidance so consistent approach in practice – use the local or direct to the PHE one with rationale on the RCGP website, and make sure used by all in the practice Use NO, or back-up antibiotic and safety net – discuss how this could be done in their practice Use the TARGET leaflet: discuss how they use leaflets and if they know about the TARGET leaflet Consider CRP to guide in difficult cases or for clinicians with particularly high antibiotic use Consider and audit of antibiotic use in acute cough using the resource on the RCGP website Complete the free RCGP RTI clinical course Can we now agree who will take these things forward and when TARGET Antibiotics Presentation - Main

35 Urinary Tract InfectionClinical scenario UTI 9 December, 2017 Urinary Tract Infection Clinical Scenario Please consider the following details:- 35 year old Strong smelling urine, Dysuria over 2 days Frequency Recent laparoscopy and removal endometriosis Had trimethoprim in the past month for suspected UTI post operation What should you ask? Presenter notes: These cases are examples that can be printed out and discussed in pairs or groups, or with the group as a whole. Find out more about the symptom severity and duration, Other urinary symptoms nocturia, haematuria, Other non-UTI symptoms – vaginal discharge, other GU symptoms, relationship to intercourse and sexual contacts, and if any symptoms of pyelonephritis – loin pain, rigors, fever. Other risk factors for antibiotic resistance or infection: hospitalisation details, perioperative complications, other antibiotics. Travel to country with high antibiotic resistance rates. TARGET Antibiotics Presentation - Main

36 Clinical scenario UTI: PHE guidance 20159 December, 2017 Urinary Tract Infection Clinical Scenario Treat women if severe/or ≥ 3 symptoms & no vaginal discharge Women mild/or ≤ 2 symptoms: pain relief, and consider delayed antibiotic prescription If cloudy urine use dipstick to guide treatment. Nitrite plus blood or leucocytes has 92% PPV; - treat Nitrite, leucocytes, blood all negative 76% NPV: Consider back-up / delayed antibiotic Urine NOT cloudy 97% negative predictive value, do not treat unless other risk factors Presenter notes: These cases are examples that can be printed out and discussed in pairs or groups, or with the group as a whole. PHE and SIGN guidance both indicate that if Severe or ≥ 3 symptoms of UTI (Dysuria, Frequency, Suprapubic tenderness, Urgency, Polyuria, Haematuria)with no vaginal discharge or irritation that 90% of these case will have a positive urine culture and therefore empirical antibiotics should be given. If mild or 2 symptoms obtain a urine culture and dipstick if cloudy. If not cloudy consider another diagnosis and a delayed ?back up antibiotic. Presenter Bring in antibiotic guidance : Use nitrofurantoin first line (if GFR over 45ml/min; GFR 30-45:only use if resistance & no alternative) as resistance & community multi-resistant ESBL increasing Trimethoprim (if low risk of resistance) and Pivmecillinam are alternative first line agents. Always safety net. In treatment failure: always perform culture So what about this case? If happy lower UTI nitrofurantoin, as post –op and recent antibiotic, it would be worth sending a urine for culture and susceptibility. If worried about pyelonephritis – co-amoxiclav Additional advice from SIGN National guidance In SIGN. Management of suspected bacterial urinary tract infection in adults: a national clinical guideline. Scottish Intercollegiate Guidelines Network Accessed RATIONALE: Diagnosis in women: expert consensus is that it is reasonable to start empirical antibiotics in women with symptoms of UTI without urine dipstick or urine culture. Diagnosis in men: a urine sample is recommended because UTI in men is generally regarded as complicated (it results from an anatomic or functional abnormality) and there are no studies on the predictive values of dipstick testing in men. Duration of treatment for men: there is no evidence to guide duration of treatment; expert consensus is that 7 days of antibiotics should be used because men are likely to have a complicating factor. Second line treatment: resistance is increasing to all antibiotics used to treat UTI, if possible antibiotic choice should be based on microbiology results. PHE guidance also at TARGET Antibiotics Presentation - Main

37 TARGET: Antibiotic and diagnostic Guides9 December, 2017 Urinary Tract Infection Clinical Scenario Antibiotic Management Guidance Fungal skin and nail infections Infectious diarrhoea H. pylori UTI Vaginal discharge Venous Leg Ulcers Presenter notes optional slide: Evidence based diagnostic guides can be found for each of the above topics If you would like to improve the diagnosis of UTI in your patients – why don’t you use the PHE diagnostic guidance flow charts. These could really help you to minimise unnecessary antibiotic use and use of dipsticks These are some of the diagnostic guides available from Public Health England, which could help you to optimise your antibiotic use. TARGET Antibiotics Presentation - Main

38 Urinary symptom – quick reference PHE guide9 December, 2017 Notes for presenter This is the UTI quick reference guide – you may wish to go to the webiste and print it off if you are intending to discuss the diagnosis of UTIs in detail in the session https://www.gov.uk/government/publications/urinary-tract-infection-diagnosis TARGET Antibiotics Presentation - Main

39 Evidence: Antibiotic resistance is increasing9 December, 2017 Urinary Tract Infection Clinical Scenario Trimethoprim resistance by age group (Welsh data) Notes for presenter This data from Welsh primary care patients (who I think would be considered similar to the rest of the UK!), shows that antibiotic resistance in organisms from urine specimens is slowly increasing, and is significantly higher in those over 80 years. This data does not represent the data for all patients presenting to you with acute uncomplicated UTI, as we know most GPs tend to only send urines to the laboratory from patients with recurrent UTI or persistent symptoms, but it certainly gives us some indication of the greater resistance in the elderly and how it is slowly increasing over time. It is likely to be about half the rate showed on this biased lab data in community patient urines. What are the implications of this data? It suggests that nitrofurantoin would be a better choice first line in acute uncomplicated UTI as resistance is lower. However nitrofurantoin should not be used if upper UTI is suspected or the eGFR is less than 45 ml/min. Another choice may be pivmecillinam if your laboratory undertakes susceptibility testing on this antibiotic. Furthermore, all patients should be told to come back to the GP if their symptoms haven't improved by 3 days or have got worse despite antibiotics. You can still use trimethoprim if you have a urine susceptibility, or the patient is younger, or your local susceptibility data indicates that resistance is very low. Alternatively you could do your own audit of your practice results, to see how may women with suspected UTI have one, what they are prescribed, the clinical outcome in your patients with UTI, and see if there has been an increase in patients returning after being given trimethoprim. Extra note for the presenter: If you have this data for your own area this will be much stronger information than presenting this information from Wales. If you send this slide to your local microbiology department they should be able to produce similar data for you. Routine laboratory data generated by the Welsh Antimicrobial Resistance Programme, Public Health Wales TARGET Antibiotics Presentation - Main

40 Urinary Tract InfectionClinical scenario UTI: Elderly patient 9 December, 2017 Please consider the following details:- 80 year old resident in nursing home Strong smelling urine, but clear looking Increasing confusion over 2 days Positive dipstick – nitrites and leucocytes No history of fever, temp 37.4°C. Has had antibiotics in past for suspected UTI What should you ask? Urinary Tract Infection Clinical Scenario Presenter notes: These cases are examples that can be printed out and discussed in pairs or groups, or with the group as a whole. See next slide for these factors below written out Ask about new or worsening urgency/incontinence, frequency suprapubic pain or flank or loin tenderness, or gross haematuria Why was she given previous antibiotics, and what were they and for how long Hydration other symptoms suggesting another infection Also look for signs of sepsis or pyelonephritis TARGET Antibiotics Presentation - Main

41 Clinical scenario UTI: Elderly patient9 December, 2017 Urinary Tract Infection Clinical Scenario 80 year old resident in nursing home Strong smelling urine, but clear looking Increasing confusion over 2 days Positive dipstick – nitrites and leucocytes No history of fever, temp 37.4°C. Has had antibiotics in the past for suspected UTI Ask about New or worsening urgency/incontinence, frequency Suprapubic pain or flank or loin tenderness, or Gross haematuria Hydration, and fluid intake other symptoms suggesting another infection Why was she given previous antibiotics, and what were they and for how long Recent hospitalisation and operations Also look for signs of sepsis or pyelonephritis Presenter notes: These cases are examples that can be printed out and discussed in pairs or groups, or with the group as a whole. The treatment of UTI in older people should follow the same principles as in younger patients and should be based on whether the infection is uncomplicated or whether there is evidence of pyelonephritis or bacteraemia. Empirical diagnosis of UTI in delirium:  For residents who do not have an indwelling catheter, minimum criteria for initiating antibiotics included acute dysuria alone or fever (>37.9ºC or 1.5ºC increase above baseline temperature) and at least one of the following: new or worsening urgency/incontinence, frequency, signs of irritation of the urinary tract such as suprapubic pain or flank or loin tenderness, or gross haematuria [Loeb et al Conf]. A positive urine culture or dipstick test will not differentiate between UTI or asymptomatic bacteriuria, and there is no robust evidence for the use of leucocyte esterase or nitrite by urine dipstick testing in the elderly [SIGN 2006]. Patients with asymptomatic bacteriuria may also have white blood cells in the urine, as the immune system does not differentiate between asymptomatic carriage and infection. In addition UTI should be considered if there are signs of septicaemia and generalized illness: nausea, vomiting, rigors, new or increasing malaise and confusion, tachycardia, tachypnoea, poor peripheral circulation, reduced urine output, low blood pressure [SIGN 2006]. There is some concern that there may be some mismanagement of cases of UTI infection in the community. By 2011 E. coli accounted for almost one third (32.2%) of all bacteraemia reports in England, with a 35% increase between 2007 and Half of E.coli bacteraeimias were from a urogenital source, half had a healthcare interaction in the prior four weeks and 10% have a urinary catheter. This suggests that a proportion of community onset bacteriuria is being missed by clinicians in the community or inappropriate antibiotics are being given. Patients or their carers should be advised to collect and commence antibiotics prescribed promptly, and what symptoms or signs should prompt them to contact their GP again. For patients with recent hospitalisation or antibiotics or operation, consideration should be given to the prescription of pivmecillinam, co-amoxiclav or ciprofloxacin over trimethoprim, but if these are prescribed always safety net and send a urine specimen for culture and susceptibility, so that treatment can be modified on receipt of the culture result. TARGET Antibiotics Presentation - Main

42 Urinary Tract InfectionClinical scenario UTI: Elderly patient: criteria for initiating antibiotics 9 December, 2017 Urinary Tract Infection Clinical Scenario 80 year old resident in nursing home Criteria for initiating antibiotics include: Acute dysuria alone OR in dementia/delirium Fever (>37.9ºC or 1.5ºC increase above baseline) AND > 1 new or worsening urgency/incontinence, frequency, signs of irritation of the urinary tract such as suprapubic pain or flank or loin tenderness, or gross haematuria Presenter notes: These cases are examples that can be printed out and discussed in pairs or groups, or with the group as a whole. National guidance indicates that older men and women should not receive antibiotic treatment for asymptomatic bacteriuria. Why is this? Mortality and the frequency of symptomatic episodes are not reduced, but for every three people given antibiotics, one will experience adverse effects (such as rash or GI symptoms) [Nicolle et al 1987]. The treatment of UTI in older people should follow the same principles as in younger patients and should be based on whether the infection is uncomplicated or whether there is evidence of pyelonephritis or bacteraemia. Signs of sepsis include: nausea, vomiting, rigors, tachycardia, new or increasing malaise and confusion, low BP, tachypnoea, poor peripheral circulation, reduced urine output. In uncomplicated UTI (i.e. believed to be without renal tract or bladder pathology) a three day course of nitrofurantoin (if eGFR>44ml/min), pivmecillinam or trimethoprim may be used in women as systematic reviews have shown that there was no significant difference in persistent UTI, clinical failure or re-infection rates but side-effects were higher in those given 7 days treatment [Lutters et al 2002]. In men again antibiotics should only be prescribed if they are symptomatic. There is no evidence to guide duration of treatment; but expert consensus is that seven days of antibiotics should be used because men are more likely to have a complicating factor, and a urine sample is recommended [Grabe et al 2009]. Empirical diagnosis of UTI in delirium: Available evidence indicates that clinicians should only start empirical antibiotics and send urine for culture if a patient has two or more signs of infection, especially dysuria, fever > 38 o or new incontinence [Benton et al 2006-Loeb et al Conf, Loeb et al 2005]. A positive urine culture or dipstick test will not differentiate between UTI or asymptomatic bacteriuria, and there is no robust evidence for the use of leucocyte esterase or nitrite by urine dipstick testing in the elderly [SIGN 2006]. Patients with asymptomatic bacteriuria may also have white blood cells in the urine, as the immune system does not differentiate between asymptomatic carriage and infection. In older patients, diagnosis should be based on a full clinical assessment, including vital signs. In patients who can explain their symptoms, dysuria (as in younger women) is the most diagnostic symptom. For residents who do not have an indwelling catheter, minimum criteria for initiating antibiotics included acute dysuria alone or fever (>37.9ºC or 1.5ºC increase above baseline temperature) and at least one of the following: new or worsening urgency/incontinence, frequency, signs of irritation of the urinary tract such as suprapubic pain or flank or loin tenderness, or gross haematuria [Loeb et al Conf]. In addition UTI should be considered if there are signs of septicaemia and generalized illness: nausea, vomiting, rigors, new or increasing malaise and confusion, tachycardia, tachypnoea, poor peripheral circulation, reduced urine output, low blood pressure [SIGN 2006]. For patients with recent hospitalisation or antibiotics or operation, consideration should be given to the prescription of pivmecillinam, co-amoxiclav or ciprofloxacin over trimethoprim, but if these are prescribed always safety net and send a urine specimen for culture and susceptibility, so that treatment can be modified on receipt of the culture result. Further notes on asymptomatic bacteriuria: In a cohort study, 318 elderly residents in care homes were followed for 9 years with urine cultures every six months [Abrutyn et al 1994]. Asymptomatic bacteriuria occurred in 25% of women >65years and 10% of men >65years. Although patients with bacteriuria had a higher mortality it was not an independent risk factor for mortality in elderly women without catheters. That is bacteriuria was an incidental finding and residents died with their bacteriuria rather than because of it. First line treatment in elderly now nitrofurantoin for 3 days If eGFR>44ml/min send urine and start pivmecillinam or trimethoprim if sensitive on recent culture Also look for signs of sepsis – if present admit TARGET Antibiotics Presentation - Main

44 Why do we need to worry about our antibiotic use in UTI?9 December, 2017 Urinary Tract Infection Clinical Scenario TARGET Antibiotics Presentation - Main

45 Evidence: Antibiotic resistance affects your patients with UTI9 December, 2017 Urinary Tract Infection Clinical Scenario Clinical outcomes of UTIs in English general practice treated with empirical trimethoprim Prospective study of 497 women (18–70 years) with ≥ 2 UTI symptoms Patients with p-value Resistant UTI Susceptible UTI Median time to symptom resolution (207) 7 days 4 days 0.0002 Re-consultation in first week or less (317) 17/44, 39% 17/273, 6% <0.0001 Further antibiotic in first week (317) 16/44, 36% 11/273, 4% Still had bacteriuria at 1 month (132) 8/19 42% 23/113, 20% 0.04 Presenter notes: So first what is the evidence that antibiotic resistance is important in your day to day practice? Maybe you could consider when you last had a patient with UTI reconsult after treatment. Pause see if there are nods or not This study looked at clinical outcome in acute uncomplicated UTI in women treated with empirical trimethoprim. Click for next part of the slide Patients with a UTI resistant to the antibiotic in the left column in red took twice as long to become asymptomatic compared to those with a susceptible organism shown in green. Furthermore 40% of those with a resistant organism reconsulted in the first week, compared to only 6% with a susceptible organism. In fact half of those patients who reconsulted in the first week had a resistant organism grown from their urine, and the majority of these had further antibiotics in that first week. And at one month 42% of those patients with a resistant organism still had the same resistant bacteria in the urine, and this would have been much greater but 11 of these 19 patients had received a second antibiotic. Extra notes for presenter, Study reference details: McNulty et al. studied whether patients with an uncomplicated community-acquired urinary tract infection (UTI) and an isolate resistant to trimethoprim had worse clinical outcomes following empirical treatment with trimethoprim 200 mg twice daily for 3 days than did those with a susceptible isolate. This was a prospective cohort study of clinical outcome where 497 women (18–70 years) presenting to general practitioner surgeries in Norwich and Gloucester with at least two symptoms of acute (<7 days) uncomplicated UTI were enrolled. Significant bacteriuria was defined as 104 cfu/mL from a mid-stream urine (MSU). The results showed that of enrolled patients, 75% (334/448) had significant bacteriuria and trimethoprim resistance was present in 13.9% (44/317) of isolates. Patients with resistant isolates had a longer median time to symptom resolution (6 versus 3 days, P = ), greater reconsultation to the practice (39% versus 6% in first week, P < ), more subsequent antibiotics (36% versus 4% in first week, P < ) and higher rates of significant bacteriuria at 1 month (42% versus 20% with susceptible isolate, P = 0.04). Half of patients reconsulting in the first week had a resistant organism. McNulty et al. J. Antimicrob. Chemother. (2006) 58 (5):  TARGET Antibiotics Presentation - Main

46 Evidence: Antibiotic use in UTI increases resistance9 December, 2017 Urinary Tract Infection Clinical Scenario Costelloe: Examined previous antibiotic use and subsequent resistance 5 studies of UTI with 14,348 patients in general practice This Forest plots shows individual study and pooled odds ratio of increased risk Antibiotic in last 6 months Increased risk (Odds Ratio) Antibiotic use decreases RESISTANCE increases RESISTANCE Steinke Any antibiotic 1.36 Donnan Trimethoprim 1.67 3.95 Hillier Amoxicillin 1.83 1.65 2.57 Metlay Sulpha / trim 4.10 Pooled results 14,348 pts 2.18 0.6 1 5 Presenters notes: So we have shown that resistance is important and is increasing – but does our antibiotic use cause increased risk of antibiotic resistant infections in our patients? This study goes some way to show that. These researchers examined 5 studies of UTI with 14,348 patients in primary care Presenter click to bring in table It found that antibiotic use in the past 6 months increased the risk of resistance two times. This forest plot shows risk of having a resistant organism if patients have had an antibiotic in the last 6 months. As you can see risk was increased in all the studies as the odds ratios (the blue squares) are to the right of the line. Presenter click to bring in text Longer duration and multiple courses of antibiotics were associated with greater resistance. What is important to note is that resistance to one antibiotic (for example amoxicillin or trimethoprim) can be linked to other resistance genes, so use of these antibiotics although considered narrower spectrum can increase resistance to other antibiotics too. Details of paper: The review included 24 studies; 22 involved patients with symptomatic infection and two involved healthy volunteers; 19 were observational studies (of which two were prospective) and five were randomised trials. In five studies of urinary tract bacteria (14 348 participants), the pooled odds ratio (OR) for resistance was 2.5 (95% confidence interval 2.1 to 2.9) within 2 months of antibiotic treatment and 1.33 (1.2 to 1.5) within 12 months. In seven studies of respiratory tract bacteria (2605 participants), pooled ORs were 2.4 (1.4 to 3.9) and 2.4 (1.3 to 4.5) for the same periods, respectively. Studies reporting the quantity of antibiotic prescribed found that longer duration and multiple courses were associated with higher rates of resistance. Studies comparing the potential for different antibiotics to induce resistance showed no consistent effects. Only one prospective study reported changes in resistance over a long period; pooled ORs fell from 12.2 (6.8 to 22.1) at 1 week to 6.1 (2.8 to 13.4) at 1 month, 3.6 (2.2 to 6.0) at 2 months, and 2.2 (1.3 to 3.6) at 6 months. Therefore in conclusion, individuals prescribed an antibiotic in primary care for a respiratory or urinary infection have increased risk of developing bacterial resistance to that antibiotic. The effect is greatest in the month immediately after treatment but may persist for up to 12 months. This effect not only increases the population carriage of organisms resistant to first line antibiotics, but also creates the conditions for increased use of second line antibiotics in the community. Longer duration and multiple courses associated with greater resistance Costelloe C et al. BMJ 2010;340:bmj.c2096 TARGET Antibiotics Presentation - Main

47 Evidence: Risk of resistance persists for at least 12 months after your prescribing9 December, 2017 Urinary Tract Infection Clinical Scenario A meta analysis of English Primary Care infections Increased risk of resistant organism Antibiotic in past 2 months Antibiotic in past 12 months UTI 5 studies: n = 14,348 2.5 times 1.33 times Presenter notes: So how long does the risk of antibiotic resistance last after a course of antibiotics? The risk of resistance is greatest in the first two months after an antibiotic as shown here for UTIs, but is still higher 12 months after antibiotic use for UTIs. Individuals prescribed an antibiotic in primary care for any infection have an increased risk of subsequently carrying resistant organisms – so that the next time they have an infection it may be with one of these antibiotic resistant organism. So in conclusion, any antibiotic increases our future risk of carrying resistant bacteria. This will be particularly so for antibiotics that attain higher concentrations in the gut. And less so for those that only concentrate in the urine, or are inactive in the gut. Details of paper: The review included 24 studies; 22 involved patients with symptomatic infection and two involved healthy volunteers; 19 were observational studies (of which two were prospective) and five were randomised trials. In five studies of urinary tract bacteria (14 348 participants), the pooled odds ratio (OR) for resistance was 2.5 (95% confidence interval 2.1 to 2.9) within 2 months of antibiotic treatment and 1.33 (1.2 to 1.5) within 12 months. In seven studies of respiratory tract bacteria (2605 participants), pooled ORs were 2.4 (1.4 to 3.9) and 2.4 (1.3 to 4.5) for the same periods, respectively. Studies reporting the quantity of antibiotic prescribed found that longer duration and multiple courses were associated with higher rates of resistance. Studies comparing the potential for different antibiotics to induce resistance showed no consistent effects. Only one prospective study reported changes in resistance over a long period; pooled ORs fell from 12.2 (6.8 to 22.1) at 1 week to 6.1 (2.8 to 13.4) at 1 month, 3.6 (2.2 to 6.0) at 2 months, and 2.2 (1.3 to 3.6) at 6 months. Therefore in conclusion, individuals prescribed an antibiotic in primary care for a urinary infection have an increased risk of carrying resistant organisms – so that the next time they have an infection it is with a antibiotic resistant organism. The effect is greatest in the month immediately after treatment but may persist for up to 12 months. This effect not only increases the population carriage of organisms resistant to first line antibiotics, but also creates the conditions for increased use of second line antibiotics in the community. Costello et al. BMJ. (2010) 340:c2096. TARGET Antibiotics Presentation - Main

49 Evidence: Antibiotics increase the risk of Clostridium difficile9 December, 2017 60% of all C.difficile diarrhoea is now community acquired – why? Significant association between any antibiotics in the past 4 weeks & C.difficile Urinary Tract Infection Clinical Scenario Community study Leeds & Truro % positive who had each antibiotic Presenters notes: Furthermore there is evidence that your antibiotic prescribing increases the risk of Clostridium difficile in your patients. In 2013 English surveillance data showed that half of all cases of C.difficile were community acquired and had no recent hospital visits. So what is causing this? There is evidence now that exposure to most antibiotics including amoxicillin increases your risk of C.difficile. Bring in first graph This case control study of 2000 patients with diarrhoea showed that 2% were positive for C.difficile toxin. Those who’d had two courses of antibiotics were at the greatest risk of C.difficile compared to controls. But patients who’d had a beta lactam, ampicillin or cephalosporin were also significantly more likely to have Clostridium difficile. Bring in second graph This second study is a very large meta-analysis of both community and hospitalised patients to see which antibiotics put you most at risk of C.difficile. All antibiotics except tetracycline (that may be protective) put patients at increased risk of C.difficile – but some more than others – and the risk increases as you go down the bar chart. Here when the authors say penicillins they mean co-amoxiclav, ampicillin and amoxicillin as well as penicillin itself. In conclusion any antibiotic will increase your patients risk of C.difficile – so we need to consider this when prescribing. Extra notes for presenter on reference Wilcox et al. estimated the incidences of community-associated CDI in 2000 in two distinct settings in England, one urban (29.5 cases per 100,000 population) and the other rural (20.2 cases per 100,000 population), by examining faecal samples (n 2,000) submitted by general practitioners from individuals with diarrhoea in the community (214). In both settings, 2.1% of samples were cytotoxin positive. Notably, hospitalization in the preceding 6 months was significantly associated with CDI (45% versus 23%; P 0.02). However, almost half of the cases had not received antibiotic therapy in the previous month, and approximately one-third had neither exposure to antibiotics nor recent hospitalization. Interestingly, contact with infants aged 2 years was significantly associated with CDI (14% versus 2%; P 0.02). Reference Deshpande et al JAC 2013 Eight studies (n¼30184 patients) met their inclusion criteria. Antibiotic exposure was associated with an increased risk of CA-CDI (OR 6.91, 95% CI 4.17–11.44, I2¼95%). The risk was greatest with clindamycin (OR 20.43, 95% CI 8.50–49.09) followed by fluoroquinolones (OR 5.65, 95% CI 4.38–7.28), cephalosporins (OR 4.47, 95% CI 1.60–12.50), penicillins (OR 3.25, 95% CI 1.89–5.57), macrolides (OR 2.55, 95% CI 1.91–3.39) and sulphonamides/trimethoprim (OR 1.84, 95% CI 1.48–2.29). Tetracyclines were not associated with an increased CDI risk (OR 0.91, 95% CI 0.57–1.45). Conclusions: Antibiotic exposure was an important risk factor for CA-CDI, but the risk was different amongst different antibiotic classes. The risk was greatest with clindamycin followed by fluoroquinolones and cephalosporins, whereas tetracyclines were not associated with an increased risk. Odds ratio for risk of C.difficiie Wilcox, Mooney et al. JAC 2008;62:388-96; Deshpande et al JAC 2013 TARGET Antibiotics Presentation - Main

50 NHS Organisation Targets for C. difficile infections:Consider: reduced 3Cs will also help reduce Clostridium difficile in the community 9 December, 2017 Urinary Tract Infection Clinical Scenario Reduce use of Ciprofloxacin Cephalosporins Co-amoxiclav Increase use of Nitrofurantoin Trimethoprim Pivmecillinam for UTI Trimethoprim still good for UTI in younger patients, or if known results Presenter notes: Reducing Clostridium in the community is a priority for many CCGs so you may wish to specifically address this in the priorities for each practice Reducing Clostridium in the community is a priority for many CCGs – you can help do this by specifically thinking about your prescribing of ciprofloxacin, cephalosporins and co-amoxiclav for UTI and only using co-amoxiclav when definitely needed. First line co-amoxiclav is only recommended for: Pyelonephritis in pregnancy Facial cellulitis or prophylaxis post dog or human bites Diverticulitis In UTI use macrodantin (which can be taken twice daily) first line unless e-GFR is below 45ml/min. Still consider trimethoprim in patients under 60 years with no risk factors for resistance. Consider pivmecillinam in the older patients if your lab undertakes susceptibility testing for it. Co-amoxiclav ONLY recommended for: Pyelonephritis in pregnancy Facial cellulitis or prophylaxis post dog or human bites Diverticulitis Persistent sinusitis second line NHS Organisation Targets for C. difficile infections: TARGET Antibiotics Presentation - Main

51 Urinary Tract Infection9 December, 2017 Quality Premium (QP) 2017/19 Urinary Tract Infection Clinical Scenario Aims to reduce gram negative bloodstream infections and inappropriate antibiotic prescribing The required performance in 2017/19 must be: A >10% reduction in number of E coli blood stream infections across primary and secondary care trimethoprim:nitrofurantoin prescribing ratio for UTI in primary care (baseline 2015/16) trimethoprim items for patients >70 years (baseline 2015/16) Sustained reduction of total antibiotics in primary care, with items /STAR-PU < 2013/14 mean. The Quality Premium (QP) was introduced in 2015/16 to reward clinical commissioning groups (CCGs) for improvements in the quality of the services that they commission and for associated improvements in health outcomes and reducing inequalities. The QP scheme was re-launched for 2016/17 and now for 2017/19 and continues to have an AMR component. The NHS England Antibiotic Quality Premium 2017/19 aims to reduce gram negative bloodstream infections and inappropriate antibiotic prescribing. The required performance in 2017/19 must be: A 10% reduction (or greater) in the number of E coli blood stream infections across the whole health economy; collection and reporting of a core primary care data set for all E coli blood stream infections. A 10% reduction (or greater) in the trimethoprim:nitrofurantoin prescribing ratio for UTI in primary care, based on CCG baseline data from 2015/16; a 10% reduction (or greater) in the number of trimethoprim items prescribed to patients aged 70 years or greater on baseline data from 2015/16. Sustained reduction of inappropriate prescribing in primary care, in which items per STAR-PU must be equal to or below England 2013/14 mean performance value. Further information is available here: https://www.england.nhs.uk/resources/resources-for-ccgs/ccg-out-tool/ccg-ois/qual-prem/ Or data is available from FingerTips: https://fingertips.phe.org.uk/ TARGET Antibiotics Presentation - Main

52 Urinary Tract Infection9 December, 2017 PHE Fingertips Urinary Tract Infection Clinical Scenario PHE Fingertips is a rich source of indicators across a range of health and wellbeing themes including AMR local indicators. With these profiles you can: Browse AMR indicators at different geographical levels Benchmark against the regional or England average Export data to use locally Compare how you are doing – lets look now! A per the previous slide, data is available from FingerTips: https://fingertips.phe.org.uk/ Data have been uploaded across six domains: Supporting NHS England Initiatives Antimicrobial Resistance (AMR) Antibiotic Prescribing Healthcare-Associated Infections (HCAI) Infection Prevention and Control (IPC) Antimicrobial stewardship (AMS) Antibiotic prescribing and antibiotic resistance are inextricably linked, as overuse and incorrect use of antibiotics are major drivers of resistance. AMR local indicators are publically available data intended to raise awareness of antibiotic prescribing, AMR, HCAI, IPC and AMS; and to facilitate the development of local action plans. The data published in this tool may be used by healthcare staff, commissioners, directors of public health, academics and the public to compare the situation in their local area to the national picture. For further information about this profile, please click here to download the user guide. TARGET Antibiotics Presentation - Main

53 TARGET Urinary Tract Infection Information leafletFor Women outside care homes with suspected UTIs or uncomplicated recurrent UTIs 9 December, 2017 Outcome and plan can be personalised Possible urinary symptoms & other things for GP & patient to consider Picture helps patients understand cause How to prevent UTIs Presenter notes: The Patient Urinary Tract Infection (UTI) Information leaflet has been designed to be used during consultation with women who have a suspected UTI It is a useful tool for clinicians to use whether the patient needs an antibiotic prescription or not. It explains the treatment decision pathway, and therefore is also helpful for less experienced staff. It includes information on the types of UTI, which are often misunderstood by patients and health care staff, illness duration, self-care advice, prevention advice and advice on when to re-consult. Use of this leaflet has been approved by PHE, RCGP, NHS Wales, Scottish UTI Network (SUTIN), RPS and BIA.  The leaflet can also be linked to your computer clinical systems Self-care & safety netting advice Flow chart helps patient understand antibiotics and resistance TARGET Antibiotics Presentation - Main

54 Percentage of public in favour of back-up delayed antibiotic prescriptions9 December, 2017 Urinary Tract Infection Clinical Scenario In % of general public reported having been given a back-up antibiotic prescription 16% of these were for suspected UTI Presenter notes: In a 2017 survey of the general public in January 2017:5% of 3,325 general public reported having been given a back-up antibiotic prescription, 16% of these were for suspected UTI Delayed antibiotics is an increasing option for suspected UTI, if milder symptoms – as 75% of women years treated for UTI in a recent UK study turned out to have negative culture. The same survey showed that 46% of the public were in favour of the use of delayed or back-up antibiotics for UTI – but a quarter were unsure and a quarter opposed, so we do need to explain the purpose of this approach carefully to patients. – using the leaflet will facilitate this. So a thorough explanation of rationale and how to collect the prescription may be needed for some patients McNulty, Butler, et al Ipsos Mori 2014 DRAFT TARGET antibiotics presentation clinical scenario based -SG CMCN amendments

56 What can you do to learn more about UTI? Use TARGET Training ResourcesTARGET antibiotics presentation 9 December, 2017 What can you do to learn more about UTI? Use TARGET Training Resources Urinary Tract Infection Clinical Scenario Managing Urinary Tract Infections Managing Acute Respiratory Tract Infections Antibiotic Resistance in Primary Care Presenter notes: These are examples of the training resources available on the TARGET antibiotics website. Each of these training tools are free and you do not need to be registered with the RCGP to use them. They also count towards your CPD. Extra presenter notes: You may wish to complete these educational modules yourself so that you can reflect on the training opportunities and give advice on how useful they are. They can be accessed here: MARTI: MUTS: Antibiotic Resistance in Primary Care: UTI: Skin Infections: Diarrhoea: Skin Infections Managing Infectious Diarrhoea

57 How could your practice improve antibiotic prescriptions for UTI?9 December, 2017 Agree antibiotic choice in line with local guidance Agree diagnostic tests in line with local laboratory Consider a non UTI cause in post-menopausal women Remember inflammation due to sexual activity can cause urinary symptoms due to mild urethritis Consider back-up prescription in those with mild symptoms Always do safety netting especially in the elderly Use the TARGET UTI patient leaflet during consultations Use computer reminders for leaflets & back-up prescriptions Do a UTI audit Do RCGP Management of UTI free online course Use stand-by rather than daily prophylaxis for recurrent UTI and review 6 monthly for need Urinary Tract Infection Clinical Scenario Presenter notes: TARGET Antibiotics Presentation - Main

58 In summary Reducing antibiotic prescribing in your practice9 December, 2017 Reducing antibiotic prescribing in your practice Makes difference to resistance in your patients Helps to slow future antibiotic resistance Increase patient self-care Helps to reduce future consulta-tions Presenter notes: Thus in summary, I hope you agree that the evidence suggests that by reducing the antibiotic prescribing in your practice – you can: Make a difference to the care of individual patients. Help to slow the development of future resistance in our community. AND as a bonus help to increase patient self-care and reduce future consultations for minor infections. TARGET Antibiotics Presentation - Main

59 Use the TARGET antibiotics toolkitPossible solution for you 9 December, 2017 How can we fit together the evidence and change behaviour during consultation with our patients to improve antibiotic prescribing? Evidence Practice Patient GP Presenter notes: So how can we fit all of this evidence together and change behaviour within the practice consultation with our patients to improve prescribing? Use the TARGET antibiotics toolkit TARGET Antibiotics Presentation - Main

60 What can and will you do? Actions 9 December, 2017Presenter notes: So what can and will you as an individual and as a practice do to help? Please can we discuss a plan? Need to discuss a plan with each practice They are all evidence based Get them to do the planning – so moves on within the practice Get them to prioritise Get them to plan review with audit. Identify a person to take forward Find the individual with computer interest and get them to help with a computer reminder linking to the TARGET patient shared information. Action plan, timescale, review date 3 year plan – as a lot going on and can’t do it all now Need to show them the scale of change which can be attained TARGET Antibiotics Presentation - Main

61 Action planning: Developing priorities, for you now9 December, 2017 Aim to start rolling back to prescribing in 2010 And halve E.coli bacteraemias HOW Use the leaflets to reduce patient expectations Develop computer prompt to increase use of leaflet Use back-up/delayed prescribing (the leaflet will help) Refer to the posters to introduce antibiotics Make sure everyone has access to antibiotic guidance Do an antibiotic audit with action planning Decide now who will be responsible for each of these agreed actions Presenter notes: The DH would like to encourage you to get back to the prescribing levels of 2010. This will help as I said to reduce Clostridium locally (and is a priority for many CCGs), and help control antibiotic resistance rates. Ask them what they are going to do: then bring up the list of things other practices have done. And see which ones they will agree to Use the leaflets to reduce patient expectations Develop computer prompt or use patient.co.uk to increase use of leaflet Use back-up/delayed prescribing (the leaflet will help) Refer to the posters to introduce antibiotics Make sure everyone including locums and trainees and nurses have access to antibiotic guidance Do an antibiotic audit Give an individual responsibility of taking these forward TARGET Antibiotics Presentation - Main

62 Many thanks 9 December, 2017 Please complete the evaluation form so we can send you your CPD certificate TARGET Antibiotics Presentation - Main