1. Session 3b: Antibiotic Stewardship
Facilitator notes:
Measures for Improvement
Session 3b: Antibiotic Stewardship
April 2018

2. Learning Objectives
Critically review measures for improvement of prescribing in terms of process and outcome
Discuss the relative merits of persuasive, restrictive and structural interventions
Critically analyse the content, availability and dissemination of policies and guidelines for antibiotic prescribing in the hospital

3. Content AMS elements Measuring the performance
Interpreting results (quality assurance)
Mesuring the intervention effect
Interventions to improve antibiotic prescribing practices for hospitalized inpatients
Barriers to intervention effect
Possible solutions

4. Antimicrobial stewardship programs ASP
The ultimate goal of an ASP is increasing the % of patients with infections who are sucessfully treated with a regimen that is minimally toxic and maximally cost-effective
Not practical outside of research setting
Components determining this outcome provide a part of the picture in the ASP assessment

5. HOW TO ASSESS THE ACTIVITIES OF ASP
Effective ASP
↑ improves appropriateness of antimicrobial use
↓ patient morbidity and mortality
↓ institutional bacterial resistance rates
↓ healthcare costs
Assessment key issues:
Goal (attainable and measurable)
Time period
Measurements
The impact of ASP on bacterial resistance can be difficult to assess due to multiple factors that can influence resistance development and spread. However there is an apparent association between antimicrobial drug use and emergence of resistance. ASP that reduces the inappropriate use of antimicrobials will decrease the selection pressure for the emergence of resistance, morbidity and mortality and finally cost.

6. HOW TO ASSESS THE ASP - measuring the performance -
Structure / Process measures:
types of recommendations, personnel involved, dedicated time
degree to which the intervention to change the use of AB has been successfully implemented (limiting inappropriate use, optimizing selection, dose, route and duration of treatment...)
Outcome measures:
adherence to guidelines,
antimicrobial drug use in volume and expenditures,
resistance rates,
% HAIs,
ADRs...
audit and feedback: few measures, but frequently fed back to the teams

7. Measures Level: Time: Metrics Population level - Aggregate
Quantity of total antimicrobial use
Antimicrobial drug expenditures
Resistance rates
Patient level
Rate of targeted antimicrobial use
Time:
Longitudinal anitimicrobial drug use
Point prevalence surveys
Metrics
DDDs
PDDs Rx
Patients reciving AB
Expenditures (local currency)

8. Interpreting results Quality assurance
Audits
Comparison of the data to some agreed upon standard (90% of patients receiving guideline-compliant th for pneumonia).
Often needed patient level data
Intrahospital comparison
Comparison of the data to the institution’s historical data or to other patient care groups in the institution (% of patients being switched from IV to PO th)
Patient level and/or aggregate (ecologic) data
Interhospital comparison / benchmarking
Used to identify potential problem areas in prescribing practice and to aid in establishing appropriate and attainable goals
Comparison of data to those obtained in similar institutions (MRSA rates)
Usually needed aggregate (ecologic) data

9. The quality of antimicrobial drug prescribing
- measured through indicators
- measurable elements of practice performance for which there is evidence or consensus that they can be used to assess quality
- judgment about the quality of care provided
- to be distinguished from performance indicators which are statistical devices for monitoring care provided

10. ANTIMICROBIAL PRESCRIBING QUALITY INDICATORS
STRUCTURE
PROCESS
OUTCOME
Hospital
Outpatient
CHOICE
DOSAGE
DURATION OF
TRETMENT/PROPHYLAXIS
TIMING
Policy, formulary
...
Morbidity, mortality
RESISTANCE
ADRs/toxicity
cost
Level of resistance

11. Improving the process has been described as the primary object of quality assessment
Results achieved represent the bottom line in defining quality

12. Possible quality indicators for antimicrobial drug use
Drug oriented
Disease oriented
Patient oriented
Structure
Presence of an antimicrobial management team
Systematic ID advice for bacteremia (guidelines)
- Systematic weekly ward round in ICUs
Process
clinical indication for all antibiotic prescriptions
Systematic day 3 reassessment
IV-oral switch criteria
- One dose only for surgical prophylaxis
- Compliance to guidelines for ICU patients
Outcome
antibiotic consumption in DDDs and local currency
% IV/oral for some antibiotics: fluoroquinolones,...
% Clostridium difficile colitis
Resistance rates
- % patients with HAI
- Incidence of VAP in ICU patients

13. Measuring the impact of interventions (study design and methods)
Interventions should be planned
Multicentre intervention studies are needed to support an optimal applicability of results
More studies should incorporate end-points related to patient survival and cost/benefits of interventions

14. Randomized controlled trials (RCTs)
The "gold standard" in research
Less used in interventions studies of antibiotic use
RCTs are resource demanding (manpower, money)
Randomization is often difficult, and subject to biases (especially one-centre studies)
" Cluster randomization" is the preferred method: hospitals are randomized, not wards within one hospital possible to control for the "contamination" bias

15. Interrupted time-series analysis (ITS)
An ITS is particularly useful when a randomized trial is not feasible or unethical
Step 1: construct a time series of rates for your particular improvement focus (antibiotic use)
Step 2:  test statistically for a change in the outcome rates in the time periods before and after the implementation
The analyses should involve several data points before and after intervention (ideally, 24 monthly rates)

16. Other analytic methods used in intervention studies
Controlled clinical trials Study of one or more intervention groups compared to one or more control groups (without randomization) Controlled before / after studies (CBAs) Prospective evaluation of outcomes in one population, before and after intervention(s) Observational studies are usually not included in reviews of intervention effects!

17. The effects of interventions: current knowledge
A majority of studies have methodological flaws!
Effect evaluation is often made difficult by considerable heterogeneity of studies
Low external validity (applicability) of results from carefully monitored studies (e.g. RCTs) is a general aspect to be considered in "real life" situations…

18. Cochrane Collaboration (Davey et al
Cochrane Collaboration (Davey et al.) "Interventions to improve antibiotic prescribing practices for hospital inpatients"
Issue published 2005: studies from 1980 up to November 2003
Issue published 2013: studies from 1980 up to December 2006
Selected for review were:
Randomized clinical trials
Interrupted time series studies
Controlled clinical trials
Controlled before-and after studies

19. Cochrane 2013: Studies overview
Type of studies:
89 studies, 95 interventions reported
56 studies (63%) used interrupted time-series analysis
25 studies (28%) were randomized controlled trials, of which 5 were cluster RCTs

20. Results 52% of studies from USA 48% from 20 other countries Aim
Decrease antibiotic treatment 74
Increase antibiotic treatment 10
Both decrease and increase 5

21. Decrease Antibiotic Treatment
Change choice of antibiotic 64 (86%) Reduce % patients exposed 3 ( 4%) Reduce duration of treatment 7 (10%) 74

22. Main categories of interventions
Persuasive interventions: use of e.g. education, feedback and reminders to change prescribers behaviour Restrictive interventions: restriction of the freedom of prescribers to select some antibiotics Majority of the 89 Cochrane studies were "multi-faceted" – that is, more than one type intervention was used, often with a mix of persuasive and restrictive components.

23. Persuasive Interventions
Direct contact with prescriber
Intervention
Studies
Multi-faceted
Least
Most
Printed materials 4
Educational meetings 2
Reminders 8
88%
Audit and feedback 10
100%
Educational outreach
Academic detailing 6
Review & recommend change 18
78%
TOTAL 48
77%

24. Restrictive Interventions
Direct contact with prescriber
Intervention
Studies
Multi-faceted (+Persuasive)
Least
Most
Compulsory order form 5
100%
Expert approval 15
25%
Removal from clinical areas 14
50%
Review and make change 4
TOTAL 38
Automatic stop order: 4 studies
Cycling: 2 studies

25. Structural Interventions
Studies
Multi-faceted (+Persuasive)
Rapid microbiology testing & PCR 4
100%
Test for inflammatory marker 3
Computerised decision support system 1
TOTAL 8

26. Summary of the main findings

27. Effect sizes of intervention categories
Persuasive interventions:
Average median effect across all study types: 3.5% – 42.5%
Restrictive interventions:
Average median effect across all study types: 34.7% – 40.5%
Importantly, restrictive interventions work faster than persuasive interventions and should be used when the need is urgent
This difference between restrictive and persuasive interventions diminishes over time ( ≥ 6 months)

28. Are intervention effects sustainable?

29. Difference in Effects Mean and 95% CI; Restrictive - Persuasive
Meta-regression of the difference in effect size between restrictive and persuasive interventions at
1, 6, 12 and 24 months after the intervention. The difference is Restrictive minus Persuasive so positive values
for the difference indicate greater effect size for Restrictive interventions and negative values indicate greater
effect size for Persuasive interventions. The bars show 95% CI for the mean difference

30. QI – Outcome - disease oriented AB use – resistance rates
2011. Klebsiella p. ESBL, ertapenem R- 28,1 %

31. 3rd generation Cephalosporins and fluoroQUinolones consumption (DDD/ 100 PD) in period of 21 month

33. Klebsiella pneumoniae ESBL ertapenem/ fluoroquinolone resistant in all Klebsiella pneumoniae ESBL isolates (%)

34. Barriers to intervention effects
Lack of infectious diseases personnel
Lack of financial resources
Inadequate health-information systems
Resistance from hospital administrators
Opposition from prescribing physicians
Physicians' lack of knowledge; cultural factors; "irrational behaviour”

36. ASP development and assessment
Identify standards
Assess current practice
Compare with standards or guidelines
Change practice to meet standards
Audits and feedback
ASP review

37. Possible solutions Local strategies tailored to the needs
Avoid the "ceiling effect": to intervene on already optimal areas
National initiatives
Innovative approaches are increasingly being sought to enhance the effect and sustainability of stewardship efforts
Computer support, electronic health records with antimicrobial stewardship modules & integrated clinical decision support
Web- or smartphone "app"-based prescriber aids
Social marketing & behaviour science theories
.....

38. Group activity Discuss
The relationship between variation in antibiotic use and variation in resistance rates / infections.
Draw on examples from your own areas of practice to illustrate that (Cl. difficile, ESBL enterobacteriaceae, Acinetobacter baumanii...)
What is the biggest problem in your settings and what has been done to change that
The impact of national initiatives on antimicrobial prescribing.

39. Facilitator notes:
Acknowledgements The creation of this training material was commissioned in 2014 by ECDC to Health Protection of Scotland, National Services Scotland, University of Chester and University of Dundee with the direct involvement of Eastaway A, C Wiuff, A Seaton, J Reilly, M Rivett. Adapted / modified by: S. Rosales Klintz, Karolinska Institutet, Stockholm, Sweden, 2015, ECDC MDRO course Diamantis Plachouras, ECDC, 2015, ECDC MDRO course Oliver Kacelnik, Norwegian Institute of Public Health, 2016, ECDC MDRO course The revision and update of this training material was commissioned in 2017 by ECDC to Transmissible (Netherlands) with the direct involvement of Rita Szabo, Remco Schrijver and Arnold Bosman

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Author: Dr Anne Eastaway, C Wiuff, A Seaton, J Reilly, Miss Michelle Rivett
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Adapted / Modified by:
S. Rosales Klintz, Karolinska Institutet, Stockholm, Sweden, 2015, ECDC MDRO course
Diamantis Plachouras, ECDC, 2015, ECDC MDRO course
Oliver Kacelnik, Norwegian Institute of Public Health, 2016, ECDC MDRO course
Rita Szabo, Remco Schrijver in collaboration with Transmissible (Netherlands), 2018
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