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Practical Guide

TO ANTIMICROBIAL STEWARDSHIP
IN HOSPITALS
Contents

Why implement antimicrobial stewardship


in hospitals ?
1. Antimicrobial use p.2
2. Combating antimicrobial resistance p.4
3. Defining antimicrobial stewardship p.6
4. G
 oals of antimicrobial stewardship
Introduction and evidence for success p.7
5. Implementation of Antimicrobial
Stewardship Programs p.11
The objective of this booklet is to provide practical
recommendations for healthcare workers in hospitals
to improve the quality of antibiotic prescribing and
thereby improve patient clinical outcomes. How to implement an Antimicrobial
Stewardship Program?
Most of the recommendations within this booklet have
been adapted from the IDSA Guidelines [Dellit et al., 2007], 1. Assess the motivations p.13
the Australian Hospital Stewardship Guidance produced 2. Ensure accountability and leadership p13
by the Australian Commission on Safety And Quality in 3. Set up structure and organization p.15
Healthcare [Duguid et al., 2010], National Stewardship Guidance
from Scotland [Nathwani et al., 2006], the UK [ DOH-ARHAI, Start smart 4. Define priorities and how to measure
progress and success p.16
then Focus, 2011] and, although less literature is available, from
other countries whenever possible. 5. Identify effective interventions for your setting p.17
6. Identify key measurements for improvement p.25
We hope that this booklet will inform, encourage and support
health professionals wishing to pursue the implementation 7. Educate and Train p.32
of antimicrobial stewardship initiatives, as well as combating 8. Communicate p.34
antimicrobial resistance.
Prof. Dilip Nathwani, MB; DTM&H, FRCP
Consultant Physician and Honorary Professor of Infection
Ninewells Hospital and Medical School Additional resources p.38
Dundee, Scotland, UK
dilip.nathwani@nhs.net

Dr Jacqueline Sneddon, MRPharmS, MSc, PhD


Project Lead for Scottish Antimicrobial Prescribing Group
Healthcare Improvement Scotland Bibliography p.40
Glasgow, Scotland, UK
jacqueline.sneddon@nhs.net

1
Animal
non-therapeutic

Why implement antimicrobial stewardship in hospitals?

Today, up to 85% of antibiotics have a non-human use and up to


75% have a non-therapeutic use. Antibiotic use in hospitals and the
community is common and often inappropriate [Figure 2]. In hospitals,
up to 50% of antimicrobial use is inappropriate [Dellit et al., 2007].

Why implement Figure 2. Unnecessary Antimicrobial Therapy.

antimicrobial stewardship 50

40
192 patients/36 Unnecessary Regimens
576 (30%) of 1941Antimicrobial Days

in hospitals? 30 33% 32%


20

16%
1. Antimicrobial use 10
10%
0
Misuse and over-use of antibiotics

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The last 50 years have witnessed the golden age of antibiotic discovery

ial inf
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ng ion
and their widespread use in hospital and community settings. Regarded

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as very effective, safe and relatively inexpensive, antibiotics have

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saved millions of lives. However, this has led to their misuse through

Co
use without a prescription and overuse for self-limiting infections
Adapted from Hecker MT. et al. Arch Intern Med. 2003;162:972-978.
[Figures 1 and 2] [Hoffman et al., 2007; Wise et al., 1999; John et al., 1997] and
as predicted by Fleming in his Nobel Prize lecture, bacterial resistance
has appeared and is growing fast [www.nobelprize.org]. Antimicrobial Prescribing Facts: The 30% Rule
~
 30% of all hospitalised inpatients at any given
Figure 1. Current use of antibiotics in the United States.
time receive antibiotics
Over 30% of antibiotics are prescribed
CDA
Human non-therapeutic Human therapeutic inappropriately in the4 community
Implementation of
infection control measures
Abx optimization
intervention Targ
6% 9% 3.5
Up to 30% of all surgical prophylaxis is
Incidence of CDAD/1000 patients-days

15% Animal therapeutic


inappropriate 3

2.5
~
 30% of hospital pharmacy costs are due to
70% Animal 2
non-therapeutic antimicrobial use
1.5
1
 0-30% of pharmacy costs can be saved by
1
antimicrobial stewardship programs
Source: www.pewhealth.org 0.5
[Hoffman et al., 2007; Wise et al., 1999; John et al., 1997]
0
1 jan 2003 1 Apr 2003 1 Apr 2004 1 Apr 2005

Four-week period
2 3
Why implement antimicrobial stewardship in hospitals?

The rising threat of antimicrobial resistance Figure 3 explains why antimicrobial resistance cannot be solved with
single interventions alone. All 3 aspects of the three pillars must
Antimicrobial resistance has been identified as a major threat by the be addressed. To ensure this happens at a hospital level requires a
World Health Organisation due to the lack of new antibiotics in the strong collaboration between infection prevention, environmental
development pipeline and infections caused by multi-drug resistant decontamination and antimicrobial stewardship teams [Moody et al., 2012].
pathogens becoming untreatable [Goossens et al., 2011; Carlet et al., 2011].
How we address this global challenge has been the subject of much
discussion and many initiatives [Carlet et al., 2012]. Figure 3. The 3 key drivers for resistance.

Antimicrobial exposure (dose, duration, type of antibiotic)


drives selection of resistant bacteria
2. Combating antimicrobial resistance
To overcome the threat of antimicrobial resistance, a three-pillar
approach has been advocated:
1 Optimise the use of existing antimicrobial agents
Antimicrobial Use
2 P revent the transmission of drug-resistant organisms through
infection control INFLUENCERS:
3 Improve environmental decontamination Human antimicrobial consumption
Agriculture antimicrobial consumption

Rationale for cohorting, private rooms, Germicides, Sub-MIC


handwashing, active surveillance residues, ionic surfactants
Double Room Double Room Double Room Double Room Room A Room A
Room A Room A Room A Room A Patient A Patient B
Patient A Patient B Patient A Patient B

Bedrail, call button, telephone,


commode, doorknob

Infection Control Environment

INFLUENCERS: INFLUENCERS:
Hand hygiene Germicides
Epidemiology 10% hypochlorite (sporicidal) for C. difficile
Outbreak investigations Cleaning Policy & Practice (What surfaces? How often?
Cohorting Is terminal cleaning enough? (NO!))
Active surveillance

White patients = Blue patients = Susceptible organism


non-infected/non-colonized infected or colonized Resistant organism
with MDRO with MDRO
Adapted from Owens RC Jr. et al. Diagn.Microbiol. and Infect. Dis. 2008; 61:110-28.

4 5
Why implement antimicrobial stewardship in hospitals?

3. Defining antimicrobial stewardship 4. G


 oals of antimicrobial stewardship and
Antimicrobial stewardship [AS] is one of the key strategies to overcome evidence for success
resistance. The four main goals of antimicrobial stewardship are listed below with
It involves the careful and responsible management of antimicrobial use. examples of evidence that stewardship programs can help achieve
these goals. [McGowan et al,. 2012; Davey P et al., (Cochrane Database), 2013]
Antimicrobial stewardship:
Goal 1: Improve patient outcomes
is an inter-professional effort, across
the continuum of care l Improve infection cure rates

involves timely and optimal selection, dose and l Reduce surgical infection rates
duration of an antimicrobial l Reduce mortality and morbidity

for the best clinical outcome for the treatment or Table 1. Example of how appropriate antibiotics improve patient
prevention of infection outcome and reduce healthcare costs.
Inappropriate Appropriate
with minimal toxicity to the patient Antibiotics Antibiotics
Characteristic (n=238) (n=522)

and minimal impact on resistance and other Demographics
Age, mean SD (yr) 57.7 15.8 59.9 16.5
ecological adverse events such as C. difficile Male 48.7% 54.2%
Chronic health state
[Nathwani et al., 2012]
Immunosuppressed 32.4% 34.3%
Chronic dialysis 14.7% 7.1%
Nursing home resident 13.4% 18.2%

Coronary artery disease 11.7% 7.9%


Chronic obstructive pulmonary disease 21.6% 17.2%
Congestive heart failure 21.6% 18.1%
Malignancy 23.1% 34.1%
Diabetes mellitus 27.5% 20,1%
The right antibiotic Charlson score, mean SD
Disease severity
4.8 3.7 4.8 3.7

for the right patient, Acute Physiology and Chronic Health


Evaluation II, mean SD
23.2 6.6 23.9 6.7

at the right time, Need for mechanical ventilation


Need for vasopressors
62.6%
59.9%
51.5%
58.0%
Organ failures, mean SD 2.3 1.0 2.2 1.1
with the right dose, and Treatment with drotrecogin alfa (activated) 3.8% 4.4%

the right route, causing


the least harm to
Infection characteristics
Nosocomial
Community-acquired
Healthcare-associated
Additional factors
69.3%
5.9%
24.8%
48.7%
11.1%
40.2%

Length of stay before infection (mean SD) 15.3 + 20.7 7.5 + 14.9
the patient and future patients Length of stay before infection (median)
Hospital mortality
9
51.7%
1
36.4%
www/cdc.gov/getsmart/healthcare/inpatient-stewardship
Adapted from Shorr AF. et al., Crit. Care Med. 2011;39:46-51.

6 7
Why implement antimicrobial stewardship in hospitals?

Goal 2: Improve patient safety Goal 3: Reduce resistance


(Minimize unintended consequences of antimicrobials)
l R estricting relevant agents can reduce colonization or infection with
l R educe antimicrobial consumption, without increasing mortality Gram-positive or Gram-negative resistant bacteria.
or infection-related readmissions e.g. 22%-36% reduction in
antimicrobial use [Dellit et al., 2007]. Figure 5. Example of a reduction of fluoroquinolone use
l Reduce C. difficile colonization or infection by controlling the use associated with decreased MRSA and fluoroquinolone-
resistant P. aeruginosa isolation rates.
of high-risk antibiotics [Valiquette et al,. 2007].
250
Figure 4. Example of robust stewardship program with strict

FQ consumption (DDD/1000 PD)


implementation of infection control measures leading to sustained 200

reduction in C. difficile infection [CDI] cases during an epidemic.


150

4 Implementation of Abx optimization CDAD 250 100

Patient-days of antibiotic use/1000 patient-days


infection control measures intervention Targeted Abx
3.5 50
200
Incidence of CDAD/1000 patients-days

3
0

Ja 000
Ja 001
Ja 02
Ja 003
Ja 004
Ja 005
Ja 006
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1.5

FQ-resistant P. aeruginosa rate (%)


1 80
50
0.5
60
0 0
1 jan 2003 1 Apr 2003 1 Apr 2004 1 Apr 2005 1 Apr 2006 40

Four-week period
20

Adapted from Valiquette L et al., Clin. Infect. Dis. 2007;45:S112-121. 0


2
3
4
5
6
Ja 7
Ja 08

Ja 9
10
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MRSA rate (%)
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34% Adapted from Lafaurie et al., J. Antimicrob. Chemother. 2012;67:1010-5.


23%
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As

23%
Why implement antimicrobial stewardship in hospitals?

Goal 4: Reduce healthcare costs 5. 4Implementation


Implementation of of Antimicrobial
Abx optimization CDAD 250

Patient-days of antibiotic use/1000 patient-days


uman non-therapeutic
(without adverselyHuman therapeutic
impacting quality of care) infection control measures intervention Targeted Abx
6% 9% 3.5Stewardship Programs
200
S avings achieved15%by reducing antibiotic costs can be greater than

Incidence of CDAD/1000 patients-days


l Animal therapeutic A recent
3 global survey outlined the range of stewardship activities
the cost of the intervention or program (from $200,000 to $900,000 across
2.5 the continents [Table 3, Figure 6]. This survey provides some
150
depending on the studies) [Dellit et al., 2007]. Such cost-effectiveness understanding about current or planned activity and barriers.
70%emerging
data are sparse but Animal [Stevenson et al., 2012; Davey et al., (Cochrane 2

Database), 2013].
non-therapeutic For1.5example, depending on the continent, stewardship programs
100
are planned in a further 20-30% of cases and funding is the most
Table 2. Example of annual savings associated with the implementation important
1
barrier. 50
of an Antimicrobial Stewardship Program. 0.5
Table 3. Implementation of Antimicrobial Stewardship Programs
Year Method A* Method B** worldwide
0 0

2000 a
158,161 229,076 1 jan 2003 1 Apr 2003 1 Apr 2004 1 Apr 2005 1 Apr 2006
North America 67%
2001 548,002 1,267,638 Europe 65% Four-week period
2002 806,393 1,446,883 Asia 53%
2003 473,174 1,354,129 Oceania 48%
South America 46%
2004 244,160 1,555,048
Africa 13%
2005 419,613 2,005,202
192 patients/36 Unnecessary Regimens
576 (30%) of 1941Antimicrobial
2006 Days
983,690 2,172,756
Figure 6. Barriers to providing a planned AMS Programme.
2007 675,036 1,990,967
33% 2008
32% 817,503 2,557,972
2009 1,278,301 2,782,519 nia
ea
29%
Oc

2010 2,175,927 3,456,373


16%
ica th

2011b 1,770,827 2,406,399 20%


er ou

10%
Am S

Yearly average 920,070 2,064,441


Total savings 10,350,787 23,224,961
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Note: data are US dollars


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April-December 2000
ha

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January-June 2011
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* Method A: Inflation rate determined using the annual US consumer price index for Medical
Co

Care Commodities.
23%
** Method B: Inflation rate determined using an Anti-Infective Specific Index (see article).
ia
As

Adapted from Beardsley J et al. Inf. Control. Hosp. Epidemiol., 2012;33:398-400. 23%
a
ric

29%
Af

0% 5% 10% 15% 20% 25% 30% 35% 40%

No barriers Administration not aware


Lack of Information Technology Higher priorities
Prescriber opposition Lack of funding/people

Table 3 and Figure 6 are adapted from First global survey of antimicrobial stewardship
(AMS), Howard P. et al., ESCMID Study Group for Antimicrobial Policies (ESGAP) & ISC
Group on Antimicrobial Stewardship ECCMID 2013, Berlin Presentation Nr. 2448.
10 11
How to implement an Antimicrobial Stewardship Program?

1. Assess the motivations


l  nalyse your situation and what problems you want to address.
A
There are many international guidelines available (see page 38),
but you will need to adapt them to your local situation.
How to implement l Define where you are and where you want to go, with
quantitative figures. One of the ways of obtaining these data is
an Antimicrobial Stewardship to measure the quantity and quality of antibiotic use (see Chapter 6).

Program?
l What can be implemented will depend on local needs/issues,
geography, available skills/expertise and other resources.
For example, easier or less costly approaches can include:
- Simple clinical algorithms
- Prescribing guidance for treatment, surgical prophylaxis
- Intravenous (IV) to oral conversion
EIGHT KEY STEPS - Provision of microbiological support
- Restricting availability of certain antibiotics (formulary restriction)
for implementing an - Automatic therapeutic substitution
Antimicrobial Stewardship Program (ASP) - IV antimicrobial batching
- Promoting education.
1 Assess the motivations [Goff et al., 2012]

2 Ensure accountability and leadership

3 Set up structure and organization 2. Ensure accountability and leadership


To ensure a successful Antimicrobial Stewardship Program:
4 Define priorities and how to measure l Theprogram should be supported by the senior hospital
progress and success management, who are accountable for the outcomes.
l A team of people and resources should be allocated by the
5 Identify effective interventions for your setting head of the organization to implement and evaluate the program.
l T he ASP team members must possess power, expertise, credibility
6 Identify key measurements for improvement
and leadership. These individuals need to convince managers
and healthcare staff of the added value of the program.
7 Educate and Train
A key component of a stewardship program is leadership and
culture of antibiotic use. This can be set out as a driver diagram
8 Communicate (see pages 14 and 16 for more details).

12 13
How to implement an Antimicrobial Stewardship Program?

Table 4. Driver Diagram Overarching Driver: Leadership and Culture. 3. Set up structure and organization
Secondary Key Change Specific Change Ideas
Driver Concepts
The key components of the structure and governance of the ASP are :
Promote Engage 1. Identify clinical providers as champions to be 1 D
 edicated resources, including dedicated personnel time for
a culture administrative and thought leaders about antibiotic stewardship.
clinical leadership stewardship activities, education, and measuring/monitoring
of optimal 2. Work with administrators to ensure that
antibiotic
to champion they understand the rationale and goals for antimicrobial use.
stewardship effort stewardship programs and interventions and
use within 2 A multidisciplinary AS team [AST] with core membership of:
provide support (financial and non-financial).
the facility
3. Engage a physician champion and core - an infectious diseases physician (or lead doctor or physician
team to enhance the focus of antimicrobial champion)
stewardship into the current process of care.
4. Bring disciplines together to improve
- a clinical microbiologist
communication and collaboration about - a clinical pharmacist with expertise in infection.
improving antibiotic use, including, as
appropriate: Other members could be specialist nurses, for example infection
- Infection preventionists; prevention or stewardship nurses, quality improvement /risk
- Hospitalists;
- Intensivists; management/patient safety managers and clinicians with an
- Emergency department physicians; interest in infection.
- Microbiologists;
- Pharmacists; 3 Governance within the hospitals quality improvement and
- Nurses; and
- Infectious disease experts. patient safety governance structure
5. Consider having the multidisciplinary group
perform a gap analysis of antimicrobial use
4 Clear lines of accountability between the chief executive,
at the facility to identify priority areas for clinical governance, drug and therapeutics committee, infection
improvement.
prevention and control committees, and the AST. Figure 7 illustrates
Adapted from www.cdc.gov/getsmart/healthcare/improve-efforts/driver-diagram/
such an organization structure.
overarching-driver

Figure 7. Model of Antimicrobial Prescribing Pathway and Organization


in Acute Hospitals in Scotland.

Medical Director Chief Executive Infection Control Manager

Drugs and Therapeutics Committee Risk Management or Patient Safety Committee


Antimicrobial
Stewardship Team
(AST) Clinical Governance Committee

Specialty-based Antimicrobial Pharmacist Infection prevention and control Committee


with responsibility for antimicrobial prescribing
Dissemination/feedback

Prescribing support/feedback
Ward Based clinical pharmacists Microbiologist/ Infectious Diseases Physician/clinician

PRESCRIBER Adapted from Nathwani D. et al., J. Antimicrob. Chemother. 2006;57:1189-1196.

14 15
How to implement an Antimicrobial Stewardship Program?

4. Define priorities and how to measure 5. Identify effective interventions


progress and success for your setting
The objectives of the ASP and how they are going to be achieved A range of stewardship interventions has been reviewed in the IDSA
and measured need to be agreed by all the key stakeholders guidelines [Dellit et al., 2007].
and communicated clearly.
When establishing a new stewardship program, it is best to start with
One way of doing this is to produce a Driver Diagram. A Driver the core strategies and focus on achieving and maintaining them
Diagram is a logic chart with three or more levels, including: before adding some of the supplemental strategies.
l A goal or vision,
l 
The high-level factors needed to achieve this goal (called
Table 5. Antimicrobial Stewardship Toolkit: Quality of Evidence to
primary drivers) support interventions.
l Specific projects and activities that would act upon these factors.
Core Strategies Supplemental Strategies
For more complex goals, each primary driver could have its own set Formulary restrictions and Streamlining / timely de-escalation
preauthorization* of therapy*
of secondary drivers (or lower level drivers).
Prospective audit Dose optimization*
Driver diagrams can help an ASP team to: with intervention and feedback*
l Explore the factors that need to be addressed to achieve a specific
Multidisciplinary stewardship team* Parenteral to oral conversion*
overall goal, Guidelines and clinical pathways*
l Show how the factors are connected, Antimicrobial order forms
l Act as a communication tool for explaining a change strategy Education
l Provide the basis for a measurement framework. Computerized decision support,
surveillance
Laboratory surveillance and feedback
Figure 8. Example of a Driver Diagram for Antimicrobial Stewardship
Combination therapies
Adapted from www.cdc.gov/getsmart/healthcare/improve-efforts/
Antimicrobial cycling
Adapted from Dellit et al. Clinical Infectious Diseases 2007; 44:159-77.
* Strategies with strongest evidence and support by IDSA.

Two core ASP strategies have emerged:

 Frontend strategies where antimicrobials are made


available through an approval process (formulary restrictions
and preauthorization).

 Back-end strategies are where antimicrobials are reviewed


after antimicrobial therapy has been initiated (prospective audit
with intervention and feedback)

16 17
How to implement an Antimicrobial Stewardship Program?

ADVANTAGES ADVANTAGES OF 5.1. Front end strategies


of FRONT-END STRATEGIES BACK-END STRATEGIES
Immediate reduction in use and Timely de-escalation of antibiotics 5.1.1. Antimicrobial Prescribing Policy
expenditure of restricted antibiotics Reduction in inappropriate use Hospital ASPs should include an Antimicrobial Prescribing Policy that
is regularly reviewed and updated.
A review of back-end versus front-end strategies reveals that A template for a hospital antimicrobial policy prepared in the UK by
back-end strategies, although more labour-intensive, are: the Specialist Advisory Committee on Antimicrobial Resistance [SACAR]
l More widely practiced and the important messages that need to be incorporated into the
policy [MINDME] are illustrated in Tables 6 and 7 from the Australian
l More easily accepted by clinicians Stewardship Guidelines [Duguid et al., 2010].
l Provide a higher opportunity for educational opportunities.
They probably provide a more sustained impact of improving the Table 6. Summary of contents of the SACAR template for hospital
antimicrobial policy.
overall quality of antimicrobial prescribing [Chung et al., 2013].
Title page
An example of such a system from Singapore is illustrated below.
name of policy, date, version, review date, and contact details
for normal hours and out-of-hours enquiries
Figure 9. Front- and Back-end Antimicrobial Stewardship Strategy.
Introduction section
FRONT-END STRATEGY BACK-END STRATEGY statement as to whether the guideline is mandatory or for guidance
only, contents and a local procedure for microbiological samples
Preauthorization Prospective audit
and restriction and feedback Summary list of available antimicrobials
unrestricted, restricted (approval of a specialist is required) or
Antibiotic prescription Antibiotic prescription
permitted for specific conditions
(by primary team) (by primary team) Regimens for treatment of common infections
treatment, prophylaxis and rules for switching from intravenous
First few doses permitted Day1: review dose and to oral administration
for selected antibiotics possibility of IV-to-oral switch
Adapted from Specialist Advisory Committee on Antimicrobial Resistance36 (SACAR)
Antimicrobial Framework. J. Antimicrob. Chemother. 2007;60:i87i90.
Day 4: review appropriateness
Institution restriction criteria considering microbiological
Continues unless intervened by ASP

for selected antibiotics culture results


Table 7. The Golden Rules of Antimicrobial Prescribing MINDME.
Day 7: review duration
of therapy M Microbiology guides therapy wherever possible
I Indications should be evidence based
Antimicrobial stewardship team or infectious diseases physician N Narrowest spectrum required
Approval Intervention to optimize D Dosage appropriate to the site and type of infection
antibiotic treatment
M Minimise duration of therapy
Patient E Ensure monotherapy in most cases
Adapted from Antibiotic Expert Group. Therapeutic guidelines: antibiotic. Version 14.
Adapted from Chung GW et al. Virulence 2013; 4:1-7. Melbourne: Therapeutic Guidelines Limited; 2010.

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How to implement an Antimicrobial Stewardship Program?

5.1.2. Clinical guidelines or care pathways 5.1.3. Formulary restrictions / approval systems
Clinical guidelines or care pathways should take into account local This involves determining the list of restricted antimicrobial agents
microbiology and antimicrobial susceptibility patterns, as well as local (broad spectrum and later generation antimicrobials) and criteria for
resource and priorities, clinician preference/views and potential risk their use combined with an approval system which is subject to
or unintended consequences. regular audit and feedback to the prescribers. It is essential that all
aspects of prescribing are supported by expert advice 24 hours a day.
Guidance on what advice to give for treatment and prophylaxis
is available in the Australian Guidelines (Table 8) although this will
depend on local burden and epidemiology. These guidelines and
policies should ideally be supported by a program of on-going
5.2. Back-end strategies
education for all relevant healthcare professionals.
5.2.1. Antimicrobial review methods
Table 8. Example of the United Kingdom Specialist Advisory Committee
on Antimicrobial Resistance recommended guidelines. Antimicrobial review methods are employed post-prescription and
outlined in the following table. The most appropriate interventions
Treatment of:
for your institution should be chosen, according to local resources.
Urinary tract infections
Upper respiratory tract infections
Table 9. Antimicrobial Review Methods.
Lower respiratory tract infections (community and hospital acquired pneumonia,
and exacerbations of chronic obstructive pulmonary disease) Commonly used
Soft tissue infections (injuries or bites, cellulitis, chronic ulcers and necrotising Review of indication for antibiotic and compliance with policy/guideline/formulary ;
fasciitis) note any recording of exception
Central nervous system infections (bacterial meningitis, viral encephalitis Review of appropriateness of antibiotic choice, dose, route and planned duration;
Gastrointestinal infections such as food poisoning and intra-abdominal sepsis review of drug allergy, review of agents that may provide duplicative therapy
Genital tract infections [potential overlapping spectra]
Bloodstream infections Review of directed therapy based on culture and susceptibility test results
Eye, ear, nose and throat infections Potential for conversion from IV to oral route
Sepsis of unknown origin Review requirement for therapeutic drug monitoring
Specific confirmed infections; for example, treatment regimens for methicillin- Review any antibiotic related adverse events
resistant Staphylococcus aureus, Clostridium difficile and tuberculosis
Endocarditis Less commonly used and
dependent on local resources
Prophylaxis use for: Clinical review by AST of specific resistant pathogens [e.g MRSA] or site of infection
Prevention of bacterial endocarditis (which patients should receive prophylaxis) [e.g blood stream infections]
Endoscopic procedures (which individuals, considered at high risk, should receive Specific review of high cost/high use/novel agents
prophylaxis; for example, neutropenic patients) Review of optimal dose [ PK/PD] in relation to dose and frequency; renal
Surgical procedures (recommendations for all common surgical interventions, adjustment, need for extended infusion, review of any potential drug interactions
including timing of initial dose and exceptional circumstances for repeat doses) Review of directed therapy based on microscopy or PCR or other rapid tests *
Splenectomy patients (provide details of both the immunisation and antimicrobial Review of empiric or directed therapy based on biomarkers *
prophylaxis requirements) * The lack of diagnosis and delay in microbiology remains a significant barrier to good stewardship and may
be a save of high cost. See Figure 10, page 27.

Adapted from Specialist Advisory Committee on Antimicrobial Resistance (SACAR)


Antimicrobial Framework. J. Antimicrob. Chemother. 2007;60:i87i90. Adapted from Johannsson B. et al. Inf. Control. Hosp. Epidemiol. 2011; 32:367-374.

20 21
How to implement an Antimicrobial Stewardship Program?

5.2.2. Audit and direct feedback to prescribers These data can be used in an audit process to provide structured
feedback to prescribing teams and to define areas for improvement.
The audit and feedback process can be managed by either the medical At a national level, as illustrated in an example for Scotland [Table 10],
infection specialist or specialist pharmacist. However, depending on such point prevalence surveys can be used to establish baseline
the intervention, specialist nurses or clinical pharmacists can also be prescribing information and identify priorities for quality
trained to support this process. improvement. This information has contributed to the development
During clinical review, a range of point-of-care stewardship of national prescribing indicators. [Malcolm et al., 2012]
interventions are useful to provide direct and timely feedback to
the prescriber at the time of prescription or laboratory diagnosis,
and provide an opportunity to educate clinical staff on appropriate Table 10. Overview of prescribing from baseline PPS (May 2009)
and follow up PPS (September 2011).
prescribing.
Baseline PPS (May 2009) Follow up PPS
(Sept 2011)
Point-of-care interventions can include:
Measure Scotland Europe Scotland
appropriate use of guidance, Acute Acute Hospitals
Hospitals
indication for antibiotic, Number of patients 7,573 73,060 11,604
surveyed
choice of agent,
Number of patients (%) 2,289 21,197 3,728
prescribed antimicrobials (30.2%) (29.0%) (32.3%)
route [IV vs. oral] of administration of treatment,
Number of patients 1,432 14,403 2,268


timeliness of treatment, (%) prescribed single (62.6%) (67.9%) (60.8%)
antimicrobial
likelihood of on-going infection or not,

Number of prescriptions 1,731 17,947 2,147


(%) for parenteral (51.8%) (60.5%) (47.8%)
use of investigation, antimicrobials

Number of prescriptions 2,538 22,456 3,811


interpretation of microbiology with a view to


(%) with indication (75.9%) (75.7%) (86.8%)
de-escalation or stopping therapy, recorded in notes

Number of prescriptions 1939 17,223 2,245


duration of therapy.


(%) compliant with local (81.0%) (82.5%) (82.8%)
policy

Number of surgical 146 927 287



The types of interventions selected, how they are delivered and by prophylaxis prescriptions (49.3%) (27.0%) (59.5%)
(%) with duration single
whom, will be determined by local resources, need and available dose
expertise.

Number of surgical 57 723 81


Feedback on antimicrobial prescribing should be provided regularly prophylaxis prescriptions (19.3%) (21.1%) (16.8%)
(%) with duration = 1 day
to prescribers in the critical care setting, and areas of high and/

Number of surgical 93 1783 114
or poor quality antimicrobial use. prophylaxis prescriptions
(%) with duration >1 day
(31.4%) (51.9%) (23.7%)
One way of evaluating prescribing within a unit or hospital is through
regular point prevalence surveys (PPS) [Ansari et al., 2009; Seaton et al., 2007] Adapted from Malcolm W, Nathwani D, et al. Antimicrob. Resist. infect. Control. 2012;2:3.

22 23
How to implement an Antimicrobial Stewardship Program?

5.2.3. Use of diagnostic tools 6.Identify key measurements


The role of rapid diagnostics and biomarkers in antimicrobial for improvement
stewardship is recognised as a key recommendation by the IDSA.
If you cannot measure it, you cannot improve it
T he IDSA policy statement for combating antimicrobial Lord Kelvin 1824-1907
resistance and saving lives recommends Greater Investment Measurement of prescribing performance is essential to evaluate
in Rapid Diagnostics R&D and Integration into Clinical Practice the impact of stewardship interventions on clinical practice and
as one of the key strategies. [Dellit et al., 2007] demonstrate benefits for patients.
Establishing what to measure, the frequency of measurement and
Figure 10. The high cost of poor diagnosis of infection.
how the data will be communicated and acted upon are also key.
Individual health Public health Overall impact
In addition to the audit and feedback described in section 5.2.2, three other
Continued Increasing burden types of measurement are commonly used within stewardship programs:
No treatment Continued illness
transmission of disease
l Surveillance of antimicrobial use and resistance.
Lack of diagnosis
l Data collection for quality improvement.
Breakdown in disease
Waste of antibiotic l Analysis of hospital datasets to evaluate positive and negative
Mis- or over-use of control and in spread
resources
Syndromic antibiotics
Antibiotic resistance
of resistant pathogen consequences of interventions.
treatment Antibiotic-related Failure of health
and C. difficile
adverse events system to treat
infection
infection
6.1. S urveillance of antimicrobial use
Integration of diagnostics with other AMS interventions, to provide fast and resistance
accurate identification and susceptibility testing, will achieve
better clinical outcomes and timely streamlining/de-escalating Monitoring trends in antimicrobial use and resistance within a hospital
of empiric broad-spectrum antibiotics in seriously ill patients. over several years and also identifying small changes in a single ward
over a one-month period, are essential to:
Many studies have assessed algorithms based on procalcitonin
l Adapt empiric treatment according to local resistance trends
(PCT) as a rapid-reacting biomarker of bacterial infection for antibiotic
stewardship. Recent systematic reviews showed benefits of PCT l Demonstrate changes in practice over time.

among patients with respiratory tract infection and sepsis by significantly l Identify wards with high antimicrobial usage or use of non-policy
reducing antibiotic exposure as well as a trend towards reduced antimicrobials and define targeted interventions required
costs and reduced length of ICU stay [Schuetz et al., 2011; Agarwal et
al., 2011; Heyland et al., 2011; Mann et al., 2011; Matthaiou et al., 2012]. Measure improvement after implemented interventions
Near-patient rapid tests, e.g. influenza, Strep A, can be useful to
Surveillance of antimicrobial use and resistance is important:
identify patients with bacterial versus viral infections.
l at hospital, local, regional, national levels (i.e.: Strama [http://
Molecular diagnostics or screening tests providing a faster en.strama.se], Wales [Heginbothom M and Howe R, 2012], Australia [www.
result play an important role in pathogen detection in critically health.sa.gov.au/INFECTIONCONTROL])
ill patients which will improve antibiotic stewardship and clinical l and at global level (i.e.: ECDC: consolidation of resistance data
outcomes [Afshari et al., 2012].
at the European level [EARSS.net] with consolidation of antibiotic
However, the availability of these interventions in resource-limited use [ESAC.net], CDC National Antimicrobial Resistance Monitoring
environments is likely to be a challenge to their introduction. System [cdc.gov/NARMS])
24 25
1.5

How to implement an Antimicrobial Stewardship Program?

DDD/1000 BD per Quarter


1.5

1.5

1.5
6.1.1. How is antimicrobial use data collected ABC Calc is a simple computer tool to measure antibiotic
1.5
and analysed? consumption in hospitals and hospital wards. It transforms aggregated
data
1.5
provided by hospital pharmacies (generally as a number
l  ntimicrobial use at individual patient level, using an electronic
A
of
1.5 packages or vials) into meaningful antibiotic utilisation rates.
prescribing system through the Hospital Information System.
[http://www.escmid.org/research_projects/study_groups/esgap/abc_calc/]
1.5
l Data from hospital pharmacy computer systems, showing

1
02
03
06 4
01
02
03
07 4
01
02
03
08 4
01
02
03
09 4
01
02
03
20 04
01
02
03
20 04
01
02
03
04
50
Pareto charts are useful to provide an overview of antimicrobial

20 0

20 0

20 0

20 0
1.5

10

11
antimicrobials delivered to each ward and used as a proxy measure

0
20
for antimicrobials administered to patients. usage at ward levelinhibitor
1.5Beta-lactam/beta-lactamase and combinations
identify wards
(J01CR) that have high total usage

DDD/1000 BD per Quarter


or1.5Cephalosporins
high use of(J01D) Carbapenems (J01DH)
restricted antimicrobials. InFluoroquinolones
the example (J01MA)
below 50%
l The measure used is Defined Daily Dose (DDD) which represents
of piperacillin/tazobactam use occurs within 3 wards therefore
the average daily maintenance dose of an antimicrobial for its main 1.5
interventions to reduce use should focus on these wards.
indication in adults. For instance, the DDD of oral amoxicillin is 1.5
1000 mg, so a patient receiving 500 mg every 8 hours for 5 days Figure 12. Pareto chart displaying use of restricted antibiotics in a
hospital
1.5 in Lanarkshire.
consumes 7.5 DDDs.

Cumulative percentage
Piperacillin/Tazobactam use in Monklands (Feb 2010)

of use
1.5 6 100
l Usage data may then be divided by a measure of hospital 5 80
Cumulative percent

No of episodes
4
activity such as number of admissions or in-patient bed days to 1.5 3
60
40
2

01
02
03
06 4
01
02
03
07 4
01
02
03
08 4
01
02
03
09 4
01
02
03
20 04
01
02
03
20 04
01
02
03
04
20 0

20 0

20 0

20 0
provide more meaningful trend analysis. In-patient bed days is

05

10

11
1 20

20
0 0
more commonly used as this data can usually be obtained earlier 18 14 5 inhibitor
Beta-lactam/beta-lactamase 4 26combinations
(ITU) 17 (J01CR)
15 ERU 2 7
Cephalosporins (J01D) Carbapenems (J01DH) No of episodes
Fluoroquinolones of use
(J01MA)
than admissions data. 50% Ward

Source: Steve McCormick, Lead Antimicrobial Pharmacist, NHS Lanarkshire - presented


l Other denominators are also used and their strengths and limitations
at Quality Improvement within Acute Medicine Workshop organized by the Scottish
have been described [Monnet et al., 2007; Berrington et al., 2010] Antimicrobial Prescribing Group and Society for Acute Medicine - June 2010.
65
Hospital level data may be transferred to a national database for
further analysis.
6.1.2.
60
55
How is antimicrobial resistance 2005
2006
data2009
2010

Cumulative percentage
Piperacillin/Tazobactam use in Monklands (Feb 2010)
50 6 collected and analyzed?
No of episodes of use
2007 2011 100
5 45 2008 80
4 Cumulative percent
60
Figure 11. Trends in Specific Antibacterial Group Usage for All-Wales Resistance data is obtained from the Microbiology laboratory through
Resistance (%)

40 3
40
35 2
hospitals from 20052011. computer1 systems. Hospital level data may then be transferred
20 to
30
0 0
1.5
national databases. Examples from two UK countries, Wales and
25 18 14 5 4 26 (ITU) 17 15 ERU 2 7
20 No of episodes of use
Scotland,
15
50%
are shown in FiguresWard
13 and 14.
DDD/1000 BD per Quarter

1.5 30 2008
10
Figure
5
13. All-Wales resistance rates for E. coli bacteraemia
2009 (2005
1.5
to 2011).
0
25 2010
3GC AMO COA CARB CXM FQ GEN PTZ
1.5 65
20
Resistance (%)

60 2005 2009
1.5 55 2006 2010
50 15 2007 2011
1.5 2008
45
10
Resistance (%)

40
1.5
35
1.5 30 5
25
1
02
03
06 4
01
02
03
07 4
01
02
03
08 4
01
02
03
09 4
01
02
03
20 04
01
02
03
20 04
01
02
03
04
50

20 0

20 0

20 0

20 0

10

11

20 0
0
20

ne

cin

cin

em

zo

rim

AG
15
a

xim

im

im

CF
Beta-lactam/beta-lactamase inhibitor combinations (J01CR)
icl

/ta
xo

xa

C/
en

op
am
ta x

zid

3G
ox

ro

ria

pip
flo

3G
10
op

en
fta

nt
fo
m

fu

Cephalosporins (J01D) Carbapenems (J01DH) Fluoroquinolones (J01MA)


ft

ro

er

m
ge
ce
-a

ce
ce

ce

cip

tri
co

5
0
3GC AMO COA CARB CXM FQ GEN PTZ
Adapted from Heginbothom M and Howe R. A Report from Public Health Wales Adapted from Heginbothom et al. A Report from Public Health Wales Antimicrobial
Antimicrobial Resistance Programme Surveillance Unit. 2012. Resistance Programme Surveillance Unit. 2012.

26 27
ntage

Piperacillin/Tazobactam use in Monklands (Feb 2010)


f use

6 100
How to implement an Antimicrobial Stewardship Program?

Figure 14. Antimicrobial resistance (with 95% confidence intervals) in Table 11. AMS program measures for quality improvement.
K. pneumoniae isolated from blood cultures in 2008 (n=512), 2009 Structural indicators
(n=672) and 2010 (n=715). Availability of multi-disciplinary antimicrobial stewardship team
Availability of guidelines for empiric treatment and surgical prophylaxis
30 2008 Provision of education in the last 2 years
2009
25 2010 Process measures
Amount of antibiotic in DDD/100 bed days
20 - Promoted antibiotics
Resistance (%)

- Restricted antibiotics
15 Compliance with acute empiric guidance (documented notes and policy
compliance)
10 % appropriate de-escalation; % appropriate switch from IV to oral
Compliance with surgical prophylaxis (<60 min from incision, <24 hours and
5 compliance with local policy
Compliance with care bundles all or nothing (3-day antibiotic review bundle,
0 ventilator-associated pneumonia, community-acquired pneumonia, sepsis)
av

in

em

zo

rim

AG
xim

on

im

im

ici

CF
c
icl

/ta
xa

C/
en

Outcome measures
op
am
tax

zid
iax

3G
ox

ro

pip
flo

3G
op

en
ftr

fta

nt
fo
m

fu

ro

er

m
ge
ce
-a

ce
ce

ce

cip

C. difficile rates
m

tri
co

Adapted from Scottish Antimicrobial Prescribing Group (SAPG), Report on Antimicrobial Surgical Site Infection (SSI) rates
Use and Resistance in Humans in 2010. Surveillance of resistance
Mortality: Standardized Mortality Rates (SMRs)
At national level, resistance surveillance is particularly important Balancing measures
Mortality
to identify emerging resistance in common pathogens or multi- SSI rates
resistant organisms such as Gram negative bacteria which produced Readmission within 30 days of discharge
extended spectrumNational
beta lactamase (ESBL) or carbapenemase enzymes.
data: compliance with indication documented
Admission to ICU
and overall median throughout data collection period
Rate of complications
100 Medical and surgical admissions Treatment-related toxicity (e.g. aminoglycoside-related toxicity)
ChangesChemother.
Adapted from Dumartin et al. J. Antimicrob. to guidance means some times Morris et al.
2011;66:1631-7;
6.2. Data
95 collection for quality are not achivable. Consultants have discussed
Inf. Control. Hosp. Epidemiol. 2012;33[3]:500-506.
this with Microbiology and Antibiotic Pharmacy.
improvement
90
Agreement reached.

6.2.1. Examplesantibiotic
ofWorking
measures
with for
ALL improvement
19 theatres
Antimicrobial
85
stewardship is part of many patient safety programs. To pharmacy reporting and 17
at 100% this month
A common quality improvement methodology is the Plan- Do-
1
-11

11

1
11

11

1
12

12
-12

M 2
-12

12
r-1

l-1

t-1
v-1

c-1

r-1

measure the performance of these programs, data is primarily used


n-

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b-

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ay

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ay
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M

100 goal =95.00

for 3 purposes [Solberg et al., 1997]: Medical median


Medical admissions Target 90 Study- Act model.
Surgical admissions Surgical median 80 Data collection
l  ccountability (e.g. targets)
A 70
60
What form
are as part How will we know Plan
of theatre checklist
we trying to that a change is
l Improvement National data: compliance with policy (antibiotic choice) 50
100 and overall median throughout data collection period 40 accomplish?
Not recording on sheet an improvement?
Medical and surgical admissions Act Do
l Research.
95 30
20 What changesReview
can wein line
make that
with SIGN guidelines +5 new theatres
A range90of such measures for antimicrobial stewardship programs have 10
0
will result in improvement?
Study
been proposed.
85 They can be summarized as four types (see Table 11):
1-2 06
3-2 07
5-2 07
7-2 07
9-2 07
11 007
1-2 07
3-2 08
5-2 08
7-2 08
9-2 08
11 008
1-2 08
3-2 09
5-2 09
7-2 09
9-2 09
11 009
1-2 09
3-2 10
5-2 10
7-2 10
9-2 0
11 010
1-2 10
3-2 11
1
01

01
0
0
0

-20
0
0
0
0
0

-20
-20

0
0
0
0

-20
0
0
0
0

-20

structural,
80 process, outcomes and balancing (are the changes causing
11

www.ihi.org/knowledge/Pages/HowtoImprove/ScienceofImprovementHowtoImprove
Month

new problems?) [www.abs-international.eu; Dumartin et al., 2011].


1
-11

11

1
11

11

1
12

12
-12

M 2
-12

12
r-1

l-1

t-1
v-1

c-1

r-1
n-

g-
p-

n-

b-

n-
ay

ar

ay
Ju

Oc
Ap

Ap
De
No
Au
Ju

Se

Ja
Fe

Ju
M
M

Quality improvement programs often use annotated run charts to display


data and show the effects of changes. Figure 15 shows an example of
a run chart used to measure improvement of administration of surgical
antibiotic prophylaxis on time.
28 29
How to implement an Antimicrobial Stewardship Program?

400

Macrolide/Lincosamide Prescriptions (millions)


Prescriptions Prescriptions

Fluoroquinolone Prescriptions (thousands)


2.5 1.75 2.5
Resistance Resistance

MRSA Resistance to Ciprofloxacin (%)


1.50

MRSA Resistance to Clindamycin (%)


300
Figure 15. Improvement in administration of on-time surgical 6.3.200 Analysis of hospital datasets 2.0
1.5
1.25
1.00
2.0
1.5
antibiotic prophylaxis. Changes to guidance means some times 1.0 0.75 1.0
are not achivable. Consultants have discussed Linkage
100 of hospital datasets such as hospital admissions, laboratory 0.5
0.50
0.25 0.5
this with Microbiology and Antibiotic Pharmacy.
Agreement reached. data 0and patient outcomes allows measurement of the impact of 0.0
-0.5
0.00
-0.25
0.0
-0.5
stewardship
-100 interventions on patient morbidity and mortality. -1.0
-0.50
-0.75 -1.0
30 Working with ALL 19 theatres -1.5 -1.00 -1.5
30 2008 -200 -1.25
antibiotic pharmacy reporting and 17
2008
2009 This provides information about effects of antimicrobial interventions -2.0 -1.50 -2.0
2009 this month
at 100%
-300 -2.5 -1.75 -2.5
25
100 25 goal =95.00
2010
2010 on clinical outcome, i.e. how restriction of cephalosporins and

n
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ar
Mr
ay
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n
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ar
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ay
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Ap

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De
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Ju

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90 fluoroquinolones has resulted in reduced Clostridium difficile

M
20
(%)

80 20 Data collection
rates by linking antimicrobial usage data and microbiology data
(%)

70
Resistance

form as part
Resistance

60 15
15 of theatre checklist [Talpaert et al., 2011, Vernaz et al., 2009, Mamoon et al., 2012].
50
40 10 Not recording on sheet
30
10 Figure 17. New cases of CDI and the number of OBDs before and after
20 5 Review in line the introduction of revised antibiotic guidelines.
10 5 with SIGN guidelines +5 new theatres
60 Introduction of revised antibiotic guidelines 15 000
0
0
0 14 000
m m 1- 06
icl ic3-l 07
ce ce av5 2a0v07
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ce ce e9-2e07
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Month

Cases/predicted values
13 000
Source: Scottish Patient Safety Program. 40
er er
co co

12 000
30

OBDs
11 000
6.2.2. Examples of measures used 20
10 000
for accountability e.g. targets 10 9 000

0
Compliance with policy is a process measure. 8 000

M 05
Ju 05
Ju 05
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5
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O ber
ve er
ce er
Ja ber

ch
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ay
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A ly
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ve er
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Figure 16.a. Indication documented in patients notes. Ap

m
National data: compliance with indication documented
National data:
and overall compliance
median with indication
throughout documented
data collection period OBD CDI Predicted values (negative binomial regression)
100 and overallMedical
medianand
throughout
surgical data collection period
admissions
100 Medical and surgical admissions OBD = Occupied Bed Days
Adapted from Talpaert et al., J. Antimicrob. Chemother.
Changes to guidance 2011;66:2168-74.
means some times
Changes to guidance means some times
95 are not achivable. Consultants have discussed
95 arewith
this not Microbiology
achivable. Consultants havePharmacy.
and Antibiotic discussed
this with Microbiology and Antibiotic
AgreementPharmacy.
90
Figure 18. Correlation between antibiotic use and resistance. reached.
Agreement reached.
90
400

Macrolide/Lincosamide Prescriptions (millions)


Working with
Prescriptions A ALL 19B theatres Prescriptions
Fluoroquinolone Prescriptions (thousands)

85 Working
antibiotic 2.5
with
pharmacy 1.75
ALL 19 theatres
reporting and 17 2.5
Resistance Resistance

MRSA Resistance to Ciprofloxacin (%)


1.50

MRSA Resistance to Clindamycin (%)


85 antibiotic pharmacy
2.0 300 reporting and 17 2.0
at 100%
1.25 this month
MM 1 1
-11-11

11 11

1 1
11 11

11 11

1 1

1 1

1 1
12 12

12 12
-12-12

MM 2 2
-12-12

12 12
r-1r-1

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at 100% this month


n- n-

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ay ay

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0.75
100 goal =95.00 1.0 1.0
Medical admissions Medical median Target 90 100 0.50
90 0.5 0.25 0.5
Medical admissions Medical median Target 80
Surgical admissions Surgical median 80 Data collection 0.0 0.00 0.0
Surgical admissions Surgical median 70 0 Data collection
form as part -0.25
70 formchecklist
as part -0.5 -0.5
Figure 16.b. Antibiotic choice compliant with policy. 60
60
of theatre
-100 of theatre checklist -1.0
-0.50
-0.75 -1.0
National data: compliance with policy (antibiotic choice) 50
100 National data:median
and overall compliance with policy
throughout (antibioticperiod
data collection choice) 50 Not recording on sheet -1.5 -1.00 -1.5
100 and overallMedical
medianand
throughout 40 -200
Not recording on sheet -1.25
surgical data collection period
admissions 40
30
-2.0 -1.50 -2.0
95 Medical and surgical admissions 30 -300 -2.5 -1.75 -2.5
95 20 Review in line
20 Review
with SIGN in line
guidelines +5 new theatres
90 10
n
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90 10 with SIGN guidelines +5 new theatres


0
85 0 Seasonal pattern of antibiotic prescriptions and MRSA, showing 1-month lag.
1-2 10-26 06
3-2 30-27 07
5-2 50-27 07
7-2 70-27 07
9-2 90-27 07
11 10107007
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3-2 30-28 08
5-2 50-28 08
7-2 70-28 08
9-2 90-28 08
11 10108008
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5-2 50-29 09
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11 10109009
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3-2 31-02 10
5-2 51-02 10
7-2 71-02 10
9-2 91-02 10
11 10110 010
1-2 11-02 10
3-2 31-12 11
1 1

85
01 01

A Mean monthly seasonal variation for quinolone prescription and MRSA isolates resistant to
0 0
0 0
0 0
0 0

-20 -20
0 0
0 0
0 0
0 0
0 0

-20 -20
-20 -20

0 0
0 0
0 0
0 0

-20 -20
0 0
0 0
0 0
0 0

-20 -20
11 11

80 Month
ciprofloxacin calculated by seasonal-trend decomposition procedures based on LOESS (STL) method.
80 Month
B Mean monthly seasonal variation for macrolide and licosamide prescription and MRSA
MM 1 1
-11-11

11 11

1 1
11 11

11 11

1 1

1 1

1 1
12 12

12 12
-12-12

MM 2 2
-12-12

12 12
r-1r-1

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resistant to clindamycin calculated by STL method. Prescription data source: IMS Health,
Note: non-zero y-axes. Xponent, 1999-2007. Resistance data source: The surveillance Network Database-USA (Focus
Source: Empirical Prescribing Indicator Report April 2011 June 2012. Scottish Antimi- Diagnostics, Hendon, VA). Abbreviation: MRSA, methicillin-resistant Staphylococcus aureus.
60 Introduction of revised antibiotic guidelines 15 000
crobial Prescribing Group August 2012. Adapted from Sun L, et al. Clin. Infect. Dis. 2012;55:687-94.
50 Move to Riverside Building 14 000
30 13 00031
d values

40
How to implement an Antimicrobial Stewardship Program?

7. Educate and Train Educating patients and the general public about hygiene and
antibiotic use is also important, and may indirectly support hospital
Education is a key component of any Antimicrobial Stewardship education efforts. National and regional public health campaigns,
Program. It should include healthcare professionals from all care including education aimed at parents and children, have had a variable
settings, as well as patients and the public. level of success [Huttner et al., 2010].
By increasing peoples knowledge and understanding of how Some examples of public awareness campaigns:
antimicrobials should be used to treat common infections and why l www.e-bug.eu
inappropriate use may lead to resistance and loss of effective treatments, l www.ecdc.europa.eu/en/eaad
this valuable resource can be protected for future generations. l www.cdc.gov/getsmart

7.1. Who should receive education 7.2. How should an education program be
in hospitals? designed?
Prescribers and other healthcare staff with modules adapted to Programs should take into account local recommendations for
their background including: antimicrobial stewardship, if available. If not, they could be inspired by
international policies (see section on Additional Resources, page 38).
l Undergraduate curriculum
Educational measures recommended in the literature to improve
l Internship
antibiotic use in hospitals are shown in Table 12.
l Professional training for new staff
Table 12. Main antimicrobial stewardship strategies recommended in the
l Continuing professional development for all prescribers international literature to improve antibiotic use at the hospital level.
l Postgraduate education Passive educational measures
Developing/updating local antibiotic guidelines
The content of education should be adapted to each profession Educational sessions, workshops, local conferences
and include: Active interventions
l Basic knowledge of infection management, Clinical rounds discussing cases
Prospective audit with intervention and feedback
l Basic microbiology
Reassessment of antibiotic prescriptions, with streamlining
l Importance of prudent prescribing in tackling antimicrobial resistance. and de-escalation of therapy
l B est practices for prescribing to support safe and effective prescribing, Academic detailing, educational outreach visits
administration and monitoring of antimicrobial therapy. Adapted from Pulcini C and Gyssens IC. Virulence 2013;4:192202.

The training is usually delivered by the antimicrobial management


team and may include competency assessment. An evaluation process should be included in the education program
to measure attendance, understanding and assimilation, using regular
training assessment tools such as attendance forms, completion
certificates, questionnaires, tests etc.

32 33
How to implement an Antimicrobial Stewardship Program?

8. Communicate Figure 20. Start Smart Then Focus approach.


Communication is a key component of the success of an ASP.
Single dose surgical prophylaxis*
Clear, simple communication should show the vision and the
benefits of the program, with core clinical messages.
Clean surgery involving
The Start Smart - Then Focus approach in the UK is a good placement of
a prosthesis or implant
example of such an approach [Figures 19 and 20]. D
O
Surgical prophylasis C
Figure 19. Start Smart Then Focus approach. Clean contaminated ONE DOSE U
surgery within 60 minutes before M
ANTIMICROBIAL STEWARDSHIP E
knife to skin
Right drug, right dose, right time, right duration N
T
every patient
Contaminated surgery
Then
focus
Start Smart Clinical review & decision* at 48 hours
* A repeat dose dose of prophylaxis may be required for prolonged procedures or where there is
Do not start antibiotics significant blood loss. A treatment course of antibiotics may also need to be given (in addition to
in the absence of evidence Clinical review check microbiology, appropriate prophylaxis) in cases of dirty surgery or infected wounds. The appropriate use and choice
of bacterial infection make and document decision* of antibiotics should be discussed with infection specialists for each case.

T ake history of relevant


allergies 1. STOP
Initiate prompt effective
2. IV/oral switch
Another approach is to identify and communicate to prescribers
antibiotic treatment within
one hour of diagnosis specific situations where antibiotics should be withheld and guidance
(or as soon as possible) 3. Change: to narrow in relation to the duration of antibiotic use, which is often an area of
in patients with life
threatening infections
spectrum agent misuse (Table 13, page 36).
C omply with local 4. Continue The importance of communicating, sharing and learning from
prescribing guidance and review
D
 ocument clinical
data is also important.
after 4 hours
indication and dose on
drug chart and clinical
Face-to-face meetings with prescribers, where there is an opportunity
5. OPAT**
notes for reflection about their prescribing practices, or attending multi-
Include review/stop disciplinary teams, web-ex conferences, etc. are all important in
date or duration
DOCUMENT DECISION promoting learning about prudent prescribing.
E nsure relevant
microbiological * Antimicrobial Prescribing Decision
** Outpatient Parenteral Therapy
specimens taken

Figures 19 and 20 are adapted from Department of Health Advisory Committee on


Antimicrobial Resistance and Healthcare Associated Infection (ARHAI) ANTIMICROBIAL
STEWARDSHIP:START SMART - THEN FOCUS Guidance for antimicrobial stewardship
in hospitals (England) November 2011.

34 35
How to implement an Antimicrobial Stewardship Program?

Table 13. Specific Situations where Antibiotics should be THE KEYS TO SUCCESS
withheld
Respiratory tract syndromes A number of interventions are key to the success of a
- Viral pharyngitis hospital-based Antimicrobial Stewardship Program.
- Viral rhinosinusitis
- Viral bronchitis
- Noninfectious cardiopulmonary disorders misdiagnosed as pneumonia Establish a clear aim/vision that is shared by all the
Acute Otitis Media (AOM) (for selected cases, refer to article) stakeholders and that conveys a sense of urgency.
Skin and Soft Tissue Infections (SSTI) Stewardship should be a patient safety priority.
- Subcutaneous abscesses (for selected cases, refer to article)
- Lower extremity stasis dermatitis
Asymptomatic bacteriuria and pyuria, including catheterized patients Seek management support, accountability
Microbial colonization and culture contamination and secure funding.
Low-grade fever
Adapted from Wlodover et al., Infect. Dis. Clin. Pract. 2012;20:12-17. 
Assemble a strong coalition including a
multi-professional antimicrobial stewardship
team with a strong influential clinical leader.
Table 14. Practice Guideline Recommendations regarding
duration of therapy
Establish effective communication structures
Community-acquired pneumonia (CAP) 5 days
within your hospital.
Health care-acquired pneumonia 8 days
Skin and Soft Tissue Infections (SSTI) 5 days
Urinary Tract Infections (UTI) Start with core evidence-based stewardship
- Cystitis 3-5 days a interventions depending on local needs,
- Pyelonephritis 5-14 days a
- Catheter associated 7 days b
geography and resources and plan measurement
S. aureus bacteremia
to demonstrate their impact.
- Low risk of complications, 2 weeks
- High risk of complications 4-6 weeks 
Ensure all healthcare staff are aware of the
Intra-abdominal infection 4-7 days
importance of stewardship. Empower them
Surgical antibiotic prophylaxis, 1 dose c
to act and support with education using a range
a
Depending on antibiotic
b
Prolonged to 10-14 days for delayed response of effective strategies.
c
Up to 24h, witout exception

Adapted from Wlodover et al., Infect. Dis. Clin. Pract. 2012;20:12-17.


Ensure early or short term wins and then
consolidate success/gains while progressing
with more change or innovation.

36 37
Additional Resources
Global Resources for implementing and measuring the impact of
hospital Antimicrobial Stewardship Programs
Department of Health Advisory Committee on Antimicrobial Resistance and
Healthcare Associated Infection (ARHAI) ANTIMICROBIAL STEWARDSHIP:
Africa START SMART - THEN FOCUS.

Antimicrobial Stewardship and Infection Control African Network : www. ESCMID Study Group for Antibiotic Policies (ESGAP): www.escmid.org/
ischemo.org/index.php/sections/isc-wg-antimicrobial-stewardship-and- index.php?id=140
infection-control-african-network Guidance for antimicrobial stewardship in hospitals (England) ARHAI
Best CareAlways! (BCA) campaign supporting South(ern) African Antimicrobial Stewardship ; http://www.dh.gov.uk/prod_consum_dh/
healthcare organisations: www.bestcare.org.za/Antibiotic+Stewardship groups/dh_digitalassets/documents/digitalasset/dh_131181.pdf

South African Antibiotic Stewardship Programme : www.fidssa.co.za/A_ Guidelines for Antimicrobial Stewardship in Hospitals in Ireland. SARI
SAASP_Home.asp Hospital Antimicrobial Stewardship Working Group http://www.hpsc.ie/
hpsc/A-Z/MicrobiologyAntimicrobialResistance/InfectionControlandHAI/
Suleman F, Meyer H. Antibiotic resistance in South Africa: your country Guidelines/File,4116,en.pdf
needs you! S. Afr. Pharm. J. 2012;79:44-46.
Monnet D, Kristinsson K. Turning the tide of antimicrobial resistance:
Europe shows the way. Euro Surveill 2008;13.
Asia-Pacific Nathwani D, on behalf of SMC/HAI. Antimicrobial prescribing policy and
practice in Scotland: recommendations for good antimicrobial practice in
Duguid M and Cruickshank M (eds) (2011). Antimicrobial stewardship
acute hospitals. J. Antimicrob. Chemother. 2006;57:1189-1196.
in Australian hospitals, Australian Commission on Safety and Quality in
Health Care, Sydney.
Ghafur A, Mathai D, Muruganathan A, et al. The Chennai Declaration US
Recommendations of A roadmap- to tackle the challenge of antimicrobial
ASHP statement on the pharmacists role in antimicrobial stewardship and
resistance - A joint meeting of medical societies of India. Indian Journal
infection prevention and control. Am. J. Health .Syst. Pharm. 2010;67:575-7.
of Cancer 2013;49.
CDC: http://www.cdc.gov/getsmart/healthcare/
Ho PL, Cheng JC, Ching PT et al. Optimising antimicrobial prescription
in hospitals by introducing an antimicrobial stewardship programme Dellit TH, Owens RC, McGowan JE, Jr. et al. Infectious Diseases Society
in Hong Kong: consensus statement. Hong Kong Med 2006;12:141-8. of America and the Society for Healthcare Epidemiology of America
Guidelines for Developing an Institutional Program to Enhance Antimicrobial
Teng CB, Lee W, Yeo CL et al. Guidelines for Antimicrobial Stewardship
Stewardship. Clinical Infectious Diseases 2007;44:159-77.
Training and Practice. Ann. Edu. Sg. 2012;41 No.1.
Drew RH, White R, MacDougall C, et al. Insights from the Society of
Infectious Diseases Pharmacists on antimicrobial stewardship guidelines
Europe from the Infectious Diseases Society of America and the Society for
Healthcare Epidemiology of America. Pharmacotherapy 2009;29:593-607.
Allenberger F, Gareis R, Jindrk V, Strulens MJ. Antibiotic stewardship
implementation in the EU: the way forward. Expert Rev. Anti Infect. Ther. Goff D, Bauer KA, Mangino JE, et al. Antibiotic stewardship management
2009;7:1175-1183. of infections. Beyond the cost of Antimicrobials. Pharmacy practice News.
August 2012:1-12 [useful suggestions for ASP in resource limited settings].
Cooke J, Alexander K, Charani E, et al. Antimicrobial stewardship: an
evidence-based, antimicrobial self-assessment toolkit (ASAT) for acute Owens RC. Antimicrobial stewardship: concepts and strategies in the
hospitals. J. Antimicrob. Chemother. 2010;65:2669-2673. 21st century. Diag. Micro. Infect. Dis. 2008;61:110-128.

38 39
Bibliography Lafaurie M, Porcher R, Donay JL, et al. Reduction of fluoroquinolone use is associated with a
decrease in methicillin-resistant Staphylococcus aureus and fluoroquinolone-resistant Pseudomonas
aeruginosa isolation rates: a 10 year study. JAC 2012;67:1010-5.
Malcolm W, Nathwani D, Davey P, et al. From intermittent antibiotic point prevalence surveys to
Afshari A, Schrenzel J, Ieven M, Harbarth S. Rapid molecular diagnostics for bloodstream infection: quality improvement: experience in Scottish hospitals. ARIC 2012;2:3.
a new frontier? Crit Care 2012;16:222. Mamoon AA, Kearney MP, Scott MG, et al. An evaluation of the impact of antibiotic stewardship
Agarwal R, Schwartz DN. Procalcitonin to guide duration of antimicrobial therapy in intensive care on reducing the use of high-risk antibiotics and its effect on the incidence of Clostridium difficile
units: a systematic review. CID 2011;53:379-387. infection in hospital settings. JAC 2012;67:29882996.
Ansari F, Erntell M, Goossens H, Davey P, et al. The European Surveillance of Antimicrobial Mann EA, Wood GL, Wade CE. Use of procalcitonin for the detection of sepsis in the critically ill
Consumption (ESAC) point prevalence survey of antibacterial use in 20 European hospitals in burn patient: a systematic review of the literature. Burns 2011;37:549-558.
2006. CID 2009;49:1496-504. Matthaiou DK, Ntani G, Kontogiorgi M, et al. An ESICM systematic review and meta-analysis of
Beardsley J et al. Show Me the Money: Long-Term Financial Impact of an Antimicrobial Stewardship procalcitonin-guided antibiotic therapy algorithms in adult critically ill patients. Intensive Care
Program, ICHE 2012;33:398-400. Med. 2012;38:940-949.
Berrington A. Antimicrobial prescribing in hospitals: be careful what you measure. JAC 2010;65:163168. McGowan JE Jr. Antimicrobial stewardship the State of the Art in 2011: Focus on Outcomes and
Methods. ICHE 2012;33:331-337.
Carlet J, Collignon P, Goldmann D, et al. Societys failure to protect a precious resource: antibiotics.
Lancet 2011;378:369-371. Monnet D. Measuring Antimicrobial Use: The Way Forward. CID 2007;44:671-673.
Carlet J et al. Ready for a world without antibiotics? The Pensires Antibiotic Resistance Call to Moody J, Cosgrove SE, Lomsted R, et al. Antimicrobial stewardship: a collaborative partnership
Action. ARIC 2012;1:11. between infection preventionists and healthcare epidemiologists. ICHE 2012;33:328-330.
Morris AM, Brener S, Dresser L, et al. Use of a structured panel process to define quality metrics
Chung GW, Wu JE, Yeo CL, et al. Antimicrobial stewardship: A review of prospective audit and
for antimicrobial stewardship programs. ICHE 2012;33(5):500-506.
feedback systems and an objective evaluation of outcomes Virulence. 2013;4:1-7.
Nathwani D, et al. Antimicrobial prescribing policy and practice in Scotland: recommendations for
Davey P, Brown E, Charani E, et al. Interventions to improve antibiotic prescribing practices for
good antimicrobial practice in acute hospitals. JAC 2006;57:1189-1196.
hospital inpatients. Cochrane Database of Systematic Reviews 2013, Issue 4. Art. No.: CD003543.
DOI: 10.1002/14651858.CD003543.pub3 Nathwani D. Antimicrobial stewardship. In: Hospital epidemiology and infection Control; Ed: C.Glen
Mayhall; 4th Edition, Philadelphia, Lippincott, Williams and Wilkins, 2012.
Dellit TH, Owens RC, McGowan JE, Jr. et al. IDSA and SHEA Guidelines for Developing an Institutional
Program to Enhance Antimicrobial Stewardship. Clin. Infect. Dis. 2007;44:159-77. Owens RC Jr. Antimicrobial stewardship: concepts and strategies in the 21st century. Diag Microbiol
Infect Dis. 2008; 61:110-28.
Department of Health Advisory Committee on Antimicrobial Resistance and Healthcare Associated
Infection (ARHAI). ANTIMICROBIAL STEWARDSHIP: START SMART - THEN FOCUS Guidance Pulcini C and Gyssens IC. How to educate prescribers in antimicrobial stewardship practices.
for antimicrobial stewardship in hospitals (England). 2011. Virulence 2013;4:192202.
Schuetz P, Chiappa V, Briel M, Greenwald JL. Procalcitonin algorithms for antibiotic therapy
Duguid M, Cruickshank M (eds) Antimicrobial stewardship in Australian hospitals. Australian
decisions: a systematic review of randomized controlled trials and recommendations for clinical
Commission on Safety and Quality in Health Care, Sydney. 2010.
algorithms. Arch Intern Med. 2011; 171:1322-1331.
Dumartin C, Rogues AM, Amado B, et al. Antibiotic usage in south-western French hospitals:
Seaton RA, Nathwani D, Burton P, et al. Point prevalence survey of antibiotic use in Scottish hospitals
trends and association with antibiotic stewardship measures. JAC 2011;66:1631-7.
utilising the Glasgow Antimicrobial Audit Tool (GAAT). Int J Antimicrob Agents 2007; 29:693-9.
Goff DA, Bauer KA, Reed EE, et al. Is the Low-Hanging Fruit Worth Picking for Antimicrobial
Shorr AF, Micek ST, Welch EC, et al. Inappropriate Antibiotic Therapy in Gram-negative Sepsis
Stewardship Programs? CID 2012;55:58792.
Increases Hospital Length of Stay. Crit Care Med. 2011;39:46-51.
Goossens H. Expert-proposed European strategies to monitor and control infection, antibiotic use, Solberg LI, Mosser G, McDonald S. The three faces of performance measurement: improvement,
and resistance in healthcare facilities. Lancet 2011;11;338-340. accountability, and research. Jt Comm J Qual Improv. 1997;23:135-47.
Hecker MT, Aron DC, Patel NP et al. Unnecessary use of antimicrobials in hospitalised patients. Stevenson KB. The economics of antimicrobial stewardship: the current state of art and applying
Arch Intern. Med 2003; 162: 972-978. the business case model. ICHE 2012;33[4]:390-397.
Heginbothom M and Howe R. Antibacterial Resistance and Usage in Wales 2005-2011. A Report Sun L., Klein EY and Laxminarayan R. Seasonality and Temporal Correlation between Community
from Public Health Wales Antimicrobial Resistance Programme Surveillance Unit. 2012. Antibiotic Use and Resistance in the United States, CID 2012;55:687-94
Heyland DK, Johnson AP, Reynolds SC, Muscedere J. Procalcitonin for reduced antibiotic exposure Talpaert MJ, Gopal Rao G, Cooper BS, Wade P. Impact of guidelines and enhanced antibiotic
in the critical care setting: a systematic review and an economic evaluation. Crit Care Med. stewardship on reducing broad-spectrum antibiotic usage and its effect on incidence of Clostridium
2011;39:1792-1799. difficile infection. JAC 2011;66:2168-74.
Hoffman JM, Shah ND, Vermuelen LC. Projecting future drug expenditures-2007. Am J Health Valiquette L, Cossette B, Garant MP et al.. Impact of a Reduction in the Use of High-Risk Antibiotics on
Syst Pharm 2007;64:298-314. the Course of an Epidemic of Clostridium difficileAssociated Disease Caused by the Hypervirulent
Huttner B, Goossens H, Verheij T, Harbarth S; CHAMP consortium. Characteristics and outcomes NAP1/027 Strain. CID 2007;45:S112-S121.
of public campaigns aimed at improving the use of antibiotics in outpatients in high-income Vernaz N, Hill K, Leggeat S, et al. Temporal effects of antibiotic use and Clostridium difficile
countries. Lancet Infect Dis. 2010;10:17-31. infections JAC 2009;63:1272-1275.
Johannsson B, Beekmann SE, Srinivasan A, et al. Improving antimicrobial stewardship : the evolution Wise R, Hart T, Cars O, et al. Antimicrobial resistance is a major threat to public health. BMJ
of programmatic strategies and barriers. ICHE 2011; 32: 367-374. 1998;317:609610.
John JF, Fishman NO. Programmatic role of the infectious diseases physician in controlling Wlodaver CG et al. Antibiotic stewardship: using clinical guidelines to control antibiotic overuse
antimicrobial costs in the hospital. CID 1997;24:471-485. and deter microbial adaptation. Infect Dis Clin Pract. 2012;20:12-17.

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