1. Use of antibiotics – how can we avert catastrophe?
Dr Damian Mawer
Clinical Microbiologist
York Teaching Hospital NHS Foundation Trust
Read through and cut down
Check Abx against local guideline
Send Mike self assessment questionnaire, scenarios on paper

2. Session Outline 14.00 Problems of antibiotic overuse
14.30 Group work (clinical scenarios)
14.40 Review clinical scenarios
15.20 End

3. Aims of this workshop Review antibiotic resistance data
28 November, 2018
Review antibiotic resistance data
Provide evidence showing the link between antibiotic prescribing and resistance in your patients
Demonstrate how reducing antibiotic prescribing can reduce antibiotic resistance, and also patient consultations
Review material available for supporting antibiotic stewardship in general practice
Discuss some clinical cases where we could improve our antibiotic prescribing
Suggest strategies and share materials
Show the evidence for using the materials
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. Balancing antibiotic benefits and risks
Bacterial resistance
Disrupt the microbiome
Superinfection (e.g. C. diff)
Side effects
Treat infection (sepsis)

5. C. Difficile infection rates are associated with antibiotic use
TARGET antibiotics presentation
C. Difficile infection rates are associated with antibiotic use
28 November, 2018
A recent Public Health England report shows that
Total (hospital and general practice combined) antibacterial consumption is highly correlated with Clostridium difficile infection rate, across Area Teams. So as antibacterial use increases, so does Clostridium difficile . This is another very good reason to only prescribe responsibly and reduce total antibiotic use, not just your broad spectrum antibiotics.
Extra notes for the presenter
This initial \PHE data suggests that about variation in total antibiotic use explains approximately 20% of the variation in Clostridium difficile across Area Teams, obviously more work needs to be done in this area to explain the reasons for the rest of the variation.
PHE surveillance data, Susan Hopkins 2014. 5

6. C. diff Vs Antibiotic Prescribng
Local C. diff trajectory was 30. Actual number of cases 33.
PHE fingertips

7. Human microbiome All body surfaces (especially the gut)
10x more cells than the body
Microbiota similar in healthy people
Disrupted by antibiotics and chemotherapy
Protects against pathogenic bacteria

9. Overuse Them, and Lose Them
"In such cases, the thoughtless person playing with penicillin is morally responsible for the death of the man who finally succumbs to infection with the penicillin-resistant organism. I hope this evil can be averted.“ Sir Alexander Fleming

15. Evidence: Antibiotic use in primary care increases resistance
TARGET antibiotics presentation
Evidence: Antibiotic use in primary care increases resistance
28 November, 2018
Antibiotic in last 6 months
Increased risk (Odds Ratio)
Antibiotic use
increases SUSCEPTIBILITY
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 antibiotic use in primary care cause increased risk of antibiotic resistant infections in our patients? Remember 80% of antibiotic prescribing is in primary care.
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 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.
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 15

16. Evidence: Risk of resistance persists for at least 12 months
TARGET antibiotics presentation
28 November, 2018
Evidence: Risk of resistance persists for at least 12 months
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
RTI
7 studies: n = 2,605
2.4 times
Presenter notes:
The risk of resistance was even greater in the first two months after an antibiotic as shown here for UTIs and Respiratory Tract infections, but was still higher 12 months after antibiotic use for both UTIs and RTIs.
Therefore in conclusion, individuals prescribed an antibiotic in primary care for a respiratory or urinary 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.
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 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. 16

17. Antibiotic resistance data from E.coli in blood cultures 2004 – 2013
TARGET antibiotics presentation
28 November, 2018
Evidence: Reducing prescribing reduces resistance
Antibiotic resistance data from E.coli in blood cultures 2004 – 2013
Ciprofloxacin
% blood culture isolates resistant
Cephalosporin
Presenter notes:
With this decrease in ciprofloxacin and cephalosporin use we have also seen a parallel decrease in resistance to ciprofloxacin and cefotaxime in blood cultures. 90% of E.coli bacteraemias are community acquired and therefore antibiotic use in the community has a great influence on these resistance rates. So congratulations – your decreased use of these agents is worthwhile and shows you can and do make a difference!
Extra presenter notes:
This is data from Public Health England.
At least 50% of bacteraemias are related to the urinary tract and 10% to urinary catheters.
The majority have had contact with a health professional in the previous 4 weeks – either in hospital or community setting. New data will be produced annually.
Livermore et al Lancet Infectious Diseases 2013 17

18. National drivers to reduce antibiotic prescribing
UK 5 year AMR Strategy
O’Neill Review: “halve inappropriate prescribing by 2020/21”
Quality Premium
Reduction in overall antibiotic prescribing
Reduction in broad spectrum prescribing (3 C’s)
Reduction in prescribing in UTI (trimethoprim: nitrofurantoin ratio, trimethoprim in patients >70)
QP for antimicrobials introduced elements: 1% reduction in total ABx prescribing, reduction in proportion of broad spectrum antibiotics (3 C’s) by 10% or below England median – 11.3%. CCG achieved both.
QP had same elements but 4% reduction on performance and 3 C’s had to be reduced by 20% versus 2014/15. Again all N Yorkshire CCG achieved both, though some individual practices didn’t manage the overall.
QP 2017/18 introduced inappropriate reduction in prescribing for UTI (driven by aim to reduce E.coli BSI). 2 elements: 10% reduction in TRI:NIT ratio. 10% reduction in TRI Px to pt >70 (both versus 2015/16 levels). Again S&R met both, but not all practices within the CCG.
QP 2018/19 is same again but no NIT:TRI ratio and greater emphasis in reducing overall prescribing.
QP credited with a 7.3% reduction in overall Abx prescribing

19. Overall prescribing
As demonstrated by the black line, antibiotic prescribing has fallen over the last 2-3yr and continues to do so.
Represents a 6% fall over 3yr in 2016.
Quality premium has undoubtedly had an impact.
Government’s Behavioural Insights Team (aka the nudge unit) also claims writing to practices with benchmarking results in also had an impact – reducing antibiotic prescription numbers by 3.3%.
Red line is Scar & Rye CCG, as some will have guessed, rate is falling but not as fast. Gap between local and national rate rising. Rachel reports CCG is struggling to hit the QP target.

20. Local CCG performance

21. Prescribing of the “3 C’s”

22. Prescribing for UTI

23. Summary
The impact of antibiotics on the microbiome may have a long-lasting impact
Antibiotic use selects for resistant bacteria which may make future infections more difficult to treat
Multi-resistant bacteria represent a local, as well as global, risk to health
Reducing prescribing to limit resistance is a national health priority

24. Questions?