Implementing antibiotic stewardship in

critical care
Jan J. De Waele MD PhD
Dept. Of Critical Care Medicine
Ghent University Hospital
Ghent, Belgium.
@CriticCareDoc

Disclosures
Financial: consultancy for AstraZeneca, AtoxBio,
Bayer, Cubist, KCI, Smith&Nephew
Academic: Sr. Clinical Investigator - Flanders
Research Fund
Societies: World Society of Abdominal
Compartment Syndrome, European Society of
Intensive Care Medicine, Belgian Society of
Intensive Care Medicine

Agenda

AB stewardship / programs (ASP)

Why do we need AB stewardship
Who is involved?
Goals of stewardship
Components of stewardship
Implementing stewardship
Conclusions

Why?
Reduce resistance
Improve patient outcome
Reduce AB side effects
Control costs

What?
Focus on rapid and
accurate diagnosis
Decrease AB exposure
Optimize PK

Antibiotic
stewardship
in ICU
Who?
Intensivist
Microbiologist / ID
Clinical pharmacist
Infection control unit

How?
Identify barriers
Choose interventions
Plan and implement
Use tools (e.g. PCT)

Why?
Reduce resistance
Improve patient outcome
Reduce AB side effects
Control costs

What?
Focus on rapid and
accurate diagnosis
Decrease AB exposure
Optimize PK

Antibiotic
stewardship
in ICU
Who?
Intensivist
Microbiologist / ID
Clinical pharmacist
Infection control unit

How?
Identify barriers
Choose interventions
Plan and implement
Use tools (e.g. PCT)

Defining AB stewardship
Antimicrobial stewardship refers to
coordinated interventions designed to
improve and measure the appropriate use of
antimicrobial agents by promoting the
selection of the optimal antimicrobial drug
regimen including dosing, duration of
therapy, and route of administration.
Quality improvement
Patient safety
SHEA. Infect Control Hosp Epidemiol 2012 4:322-327

Goals of AB stewardship
Improve outcomes

Minimize toxicity
Reduce antibiotic resistance
Reduce costs
SHEA. Infect Control Hosp Epidemiol 2012 4:322-327

Integrated in other strategies

Introduction
Relevant in ICU patients
Difficult to treat infections
Prone to side effects
Increasing AB resistance
Focus on early antibiotic therapy and
adequate spectrum

Integrated in other strategies

ANTIBIOTIC USE IN CRITICAL CARE

70%

30-60%

Of patients receive
antibiotics each day in
our ICUs

Is inappropriate,
unnecessary or
suboptimal

Vincent, JL. JAMA 2009 21:2323-2329

Luyt, CE. Crit Care 2014 5:480

AB use in ICU
Little room for mistakes
Early appropriate therapy crucial
But only in septic shock
Complexity of diagnostic process also for
non-intensivists
Multiple infections
Role of type of ICU? Closed vs. open
Dedicated intensivists 24/7 coverage

MDR - XDR - PDR

MDR

XDR

PDR

Martn-Loeches, I. Curr Opin Crit Care 2014 5:516-524

Epidemiology of MDR
Klebsiella pneumoniae carbepemase

Munoz-Price, LS. Lancet Infect Dis 2013 9:785-796

Epidemiology of MDR in our ICUs

MDR a reality
XDR emerging

Local epidemiology
variable
Outbreaks mostly
Prevalence high in Out of control in
many other
some hospitals
countries
Limited therapeutic
options

PDR threat

Start of the post

antibiotic era
Near future?

The complexity of resistance

JPIAMR Strategic research agenda

We need to use our AB wisely

Increasing
resistance

Few new
drugs

Poor
outcomes

Why?
Reduce resistance
Improve patient outcome
Reduce AB side effects
Control costs

What?
Focus on rapid and
accurate diagnosis
Decrease AB exposure
Optimize PK

Antibiotic
stewardship
in ICU
Who?
Intensivist
Microbiologist / ID
Clinical pharmacist
Infection control unit

How?
Identify barriers
Choose interventions
Plan and implement
Use tools (e.g. PCT)

Who is involved?

ID-Physician
Clinical pharmacist
Clinical microbiologist
Infection preventionist
Information system specialist

Hospital administration support staff

leadership support
Adequate authority
Dellit, TH. Clin. Infect. Dis. 2007 2:159-177

Crucial partners in ASP

Infection control
Prevention of spread key issue
Hand hygiene
Targeted screening
Isolation
Barriers multiple

Crucial partners in ASP

Microbiology lab
Short turn-around times
Rapid identification eg MALDITOF
PCR to detect resistance genes
MIC determination still takes time
Direct susceptibility testing
Communication

Why?
Reduce resistance
Improve patient outcome
Reduce AB side effects
Control costs

What?
Focus on rapid and
accurate diagnosis
Decrease AB exposure
Optimize PK

Antibiotic
stewardship
in ICU
Who?
Intensivist
Microbiologist / ID
Clinical pharmacist
Infection control unit

How?
Identify barriers
Choose interventions
Plan and implement
Use tools (e.g. PCT)

Elements of ABS programs

Active strategies
Audit with intervention and feedback A - I
ID or pharmacists
Results in reduced inappropriate use of
AB
Help of computer surveillance
Focus on specific services

Dellit, TH. Clin. Infect. Dis. 2007 2:159-177

Elements of ABS programs

Active strategies
Formulary restriction and preauthorization
Very effective in controlling AB use A - II
Useful in outbreaks B - II
Depends on who still can use the drug
Overall consumption to be considered

Dellit, TH. Clin. Infect. Dis. 2007 2:159-177

Elements of ABS programs

Additional strategies
Education A - III
Frequently used and essential
Teaching sessions, guideline development,

Little use when isolated active

intervention needed

Dellit, TH. Clin. Infect. Dis. 2007 2:159-177

Elements of ABS programs

Additional strategies
Guidelines A - I
Very popular
National vs local
Impact on behaviour?
Multidisciplinary involvement

Dellit, TH. Clin. Infect. Dis. 2007 2:159-177

Local ecology to guide therapy

De Bus, L. Crit Care 2014 4:R152

Elements of ABS programs

Additional strategies
Antibiotic order form B - II
Justification for antibiotic use
Automatic stop orders
In the ICU - questionable
Can delay therapy
Daily review necessary
Dellit, TH. Clin. Infect. Dis. 2007 2:159-177

Elements of ABS programs

Additional strategies
Combination therapy
No routine use to prevent resistance C - II
Exceptions eg ICU A - II
In the ICU
May be required and improve outcome
Discouraging combination therapy
potentially dangerous
Dellit, TH. Clin. Infect. Dis. 2007 2:159-177

Elements of ABS programs

Additional strategies
De-escalation of therapy A-II
Reduction of number of antibiotics or
spectrum

In the ICU
Difficult to do around 20-50% max
Longer duration of antibiotics
Impact on ABR unclear
Dellit, TH. Clin. Infect. Dis. 2007 2:159-177

Elements of ABS programs

Additional strategies
Dose optimisation A-II
Based on changed PK
Antibiotic resistance
In the ICU
Optimized/personalized dosing
PKPD principles
Important potential
Dellit, TH. Clin. Infect. Dis. 2007 2:159-177

Keep PKPD targets in mind

Roberts JA, Crit Care Med 2009 37: 840-51.

Do we need a loading dose?

Compensate for increased Vd
Crucial when giving anything in prolonged
infusion
Less data in case of intermittent dosing
Also in AKI, also in RRT

Optimizing maintenance therapy

Prolonged infusion of beta-lactam antibiotics
DALI study: 3 to 4 times more likely to
attain PKPD targets
Better target attainment for borderline
susceptible pathogens
Clinical evidence lacking
Studies underway

De Waele, JJ. Int J Antimicrob Agents 2015 5:461-463

De Waele, JJ. Intensive Care Med 2014 9:1340-1351

Elements of ABS programs

Additional strategies
Conversion parenteral to enteral
Bioavailability good for many antibiotics
In the ICU
Lack of data
PK often compromised
? Impact on LOS
Dellit, TH. Clin. Infect. Dis. 2007 2:159-177

Elements of ABS programs

ICT support
Electronic patient record
CPOE
Decision support
In the ICU
Integrated in PDMS
Easy surveillance
Dellit, TH. Clin. Infect. Dis. 2007 2:159-177

Elements of ABS programs

Microbiology lab
Crucial role
Rapid diagnostics and reporting
In the ICU
Short lines of communication
New technologies on the horizon - PCR
based
Dellit, TH. Clin. Infect. Dis. 2007 2:159-177

Electronic
ICT support
Electronic patient record
CPOE
Decision support
In the ICU
Integrated in PDMS
Easy surveillance
Dellit, TH. Clin. Infect. Dis. 2007 2:159-177

Impact of ASPs

Schuts, EC. Lancet Infect Dis 2016

Impact of ASPs

Schuts, EC. Lancet Infect Dis 2016

Schuts, EC. Lancet Infect Dis 2016

Impact of ASPs

Schuts, EC. Lancet Infect Dis 2016

Why?
Reduce resistance
Improve patient outcome
Reduce AB side effects
Control costs

What?
Focus on rapid and
accurate diagnosis
Decrease AB exposure
Optimize PK

Antibiotic
stewardship
in ICU
Who?
Intensivist
Microbiologist / ID
Clinical pharmacist
Infection control unit

How?
Identify barriers
Choose interventions
Plan and implement
Use tools (e.g. PCT)

How to develop an ASP

Baseline situation critical

Identify local experts
Involve local champions
Identify unit/institution weaknesses

Evidence for interventions variable

One bundle may reduce quality of care in
other areas

Consider the setting

Local antibiotic use

Ecology
Resources
Guideline adherence

Consensus building
SHEA. Infect Control Hosp Epidemiol 2012 4:322-327

Geographical differences

Resistance
Pathogens causing infection
Antibiotic use
Institution culture
Infection control practices

May impact ASP activities

Differences in resistance
Proportion of Piperacillintaz Resistant (R)
Pseudomonas aeruginosa Isolates in Participating
Countries in 2014

Variability in microbiology
Principal pathogens in VAP
60

50

40

30

20

10

0
SP

GR
Staf. Aureus

FR
Pseud aer

TK
Klebsiella

BE

IRE

Acinetobacter

Koulenti, D. Crit Care Med 2009 8:2360-2368

Differences in antibiotic use

This report has been generated from ESAC-Net data submitted to TESSy, The European Surveillance System on 2015-12-01

Differences in antibiotic use

This report has been generated from ESAC-Net data submitted to TESSy, The European Surveillance System on 2015-12-01

Variability in guideline availability

Kaier, K. BMC Infect Dis 2014 199

Variability in infection prevention

Oral chlorhex routine

Inf Control Interaction

Ricard, JD. J Infect 2012 4:285-291

Specific targets in the ICU

Multidrug regimens with redundant
antimicrobial spectra
Antibiotic therapy for nonbacterial
syndromes or colonization
Empiric regimens that are either
inadequately or excessively broad
Regimens that are not adequate for
culture positive inections

SHEA. Infect Control Hosp Epidemiol 2012 4:322-327

How to proceed

Be involved
Audit your unit
Get support from your colleagues
Set priorities
Communicate
Educate
Compose your a-la-carte ASP
Measure

ICU and ASP

Infection management important part of
ICU care
Complexity of critical illness role of
source control
Patient physiology is different
Acknowledge the determinants of AB
prescription
Less not necessarily more
Specific therapies available eg inhaled
antibiotics

Data collection crucial

Measure and monitor AB use
Surveillance of local epidemiology
Benchmarking

SHEA. Infect Control Hosp Epidemiol 2012 4:322-327

Potential drawbacks of ASP

Reduces knowledge and involvement of
clinicians
Fails to appreciating complexity in ICU
patients
Decreases our attention for other
priorities
Source control
Other bundles eg sedation, nutrition,
glucose control,

Key messages

Goals of ASP highly desirable

Antibiotic consumption problematic
Multidisciplinary approach key feature
Intensivists needs to be involved
Different strategies relevance may vary
Analyse local situation
Get support colleagues, ID, pharmacy, lab
Choose your ASP components

Thank you for your attention

Email: Jan.DeWaele@UGent.be
@CriticCareDoc