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Faculty/Presenter Disclosure
• Faculty: Jan DE WAELE
• Relationships with commercial interests: – Grants/Research Support: Sr. Clinical Researcher Fund Scientific
Research
– Speakers Bureau/Honoraria*: Accelerate, Bayer Healthcare, Grifols, MSD
– Consulting Fees*: AtoxBio, Bayer Healthcare, Cubist, MSD, Pfizer
– Other: none
* Fees and honoraria paid to institution
70% Of patients receive
antibiotics each day in our ICUs
30-60% Is inappropriate, unnecessary or
suboptimal
Vincent, JL. JAMA 2009 21:2323-2329
Luyt, CE. Crit Care 2014 5:480
ANTIBIOTIC USE IN CRITICAL CARE
Antibiotic stewardship program goals
Decreased antibiotic exposure
Reduced antibiotic resistance
Unchanged outcomes
Less side effects Reduced costs
Infection, inflammation and sepsis
• Inflammation is a common finding in the ICU
• SIRS criteria
• Lack of good biomarkers or scores
• Too many antibiotics for low-probabilty
infections, culture negative infection,
prophylaxis
Antibiotic stewardship at the bedside
• Empirical therapy selection
• Documentation
Initiation of therapy
• TDM
• De-escalation and streamlining
During therapy • AB duration
End of therapy
Antibiotic stewardship at the bedside
• Empirical therapy selection
• Documentation
Initiation of therapy
• TDM
• De-escalation and streamlining
During therapy • AB duration
End of therapy
Think ahead.
Think ahead – document
Rationale
• Suspected focus
• Clinical conditions
• Organ dysfunction
• Rationale for choice
• Enter details in patient file
Infection
• Microbiological sampling
• Haemocultures
• Before antibiotics
• Appropriate methodology
• Discuss with microbiology if needed
Antibiotic stewardship at the bedside
• Empirical therapy selection
• Documentation
Initiation of therapy
• TDM
• De-escalation and streamlining
During therapy • AB duration
End of therapy
Defining de-escalation
1. Reduce the number of antibiotics
→ Aimed at causative pathogen
→ Not aimed at causative pathogen
2. Narrow the spectrum
3. Shorten duration
4. Stop AB without infection
Defining de-escalation
1. Reduce the number of antibiotics
→ Aimed at causative pathogen
→ Not aimed at causative pathogen
2. Narrow the spectrum
3. Shorten duration
4. Stop AB without infection
Ranking antibiotics in de-escalation
Weiss, E. Clin Microbiol Infect 2015 7:649.e1-10
ADE in pneumonia
Data consistent with other indications for antibiotic therapy
Frequency of de-escalation limited
→ 10 – 50 %
Lower mortality in studies (prospective and retrospective)
→ Lower severity of illness
→ Marker of clinical improvement
Determinants of failure to de-escalate
→ Inconclusive microbiology, MDR pathogens, severe disease
ADE in pneumococcal CAP
De-escalation: spectrum narrowed to PEN, AMX, AMC within 72h
166/1410 (12%) – almost no de-escalation in ICU patients
No higher mortality (overall 5%), but shorter LOS and shorter duration of IV antibiotic therapy
Also for PSI IV and V, bacteriemic pneumonia and instable patients
PS little if any de-escalation before 2000
Viasus, D. J Antimicrob Chemother 2017 2:547-5553
ADE in ventilated pneumonia
De-escalation: spectrum narrowed, number reduced
140/283 (50%)
Setting of ‘high level antibiotic stewardship’
No impact of ’enhanced antibiotic de-escalation’ policy
Trend towards lower mortality in de-escalated patients
No difference in antibiotic days
No difference in LOS
Trupka, T. Crit Care 2017 1:180
ADE in VAP
De-escalation: spectrum narrowed of the pivotal beta-lactam AB
70/182 (38%), 87% of which within 72h – interestingly
enough possible in 72%
No difference in VAP relapse, duration of ventilation, ICU LOS
or mortality
No impact on carbapenems but lower Class 4 (TZP, …) AB use
Trend towards less ESBL-Enterobacteraceae
Weiss, E. Intensive Care Med 2016 12:2098-
2100
Enhancing de-escalation in your unit
1. Agree on a definition/classification and target patient
population
2. Identify the optimal time – late de-escalation is not
recommended
3. Check if you have the necessary data available at
48-72h
→Diagnostic sampling, microbiology link
4. Collaborative approach
5. High sense of ownership by intensivists
Antibiotic stewardship at the bedside
• Empirical therapy selection
• Documentation
Initiation of therapy
• TDM
• De-escalation and streamlining
During therapy • AB duration
End of therapy
Duration of antibiotic therapy
• Jpg van klok onder stof en rags
Duration - VAP
19© All rights reserved ESICM 2015
Duration - VAP
Pugh, R. Cochrane Database Syst Rev 2015 CD007577
Pugh, R. Cochrane Database Syst Rev 2015
CD007577
Duration of antibiotic therapy - VAP
Multiple RCTs available - fixed duration of therapy
Short course (7-8 days) compared to longer duration
Short-course antibiotic therapy recommended
More antibiotic free days
Less MDR recurrent pneumonia
No impact on other relevant outcomes
NF-GNB – similar findings in updated meta-analysis
Duration of antibiotic therapy - HAP
• Few relevant data to
guide decision making
in HAP
• Extrapolation of VAP
data
• Short course
recommended – 7 days
for most patients
Exceptions to the rule
• Immunodeficient patients
• Cystic fibrosis
• Empyema and abscess
• Necrotizing pneumonia
• XDR pathogens
• Lack of clinical improvement
Duration of antibiotic therapy - caveats
Clinical evolution is critical to determine antibiotic use
Tools to guide decision making
Procalcitonin
→Mostly combined with clinical criteria
→Shorter duration of antibiotic therapy
• Modest 1-2 days in studies
→Impact on outcome
• Mechanism unclear
Duration of antibiotic therapy - CAP
Broad spectrum of severity
Duration of limited interest to intensivists
Still our responsibility
Clear instructions at discharge
Consensus 5-7 days for most patients
Shorter course (5d) in low severity patients who have substantially
improved and are treated with BL or FQ
Longer courses for Legionella (7-10d), atypical pneumonia
(14d), S. Aureus (14d)
Limiting duration in your unit
• Document indication, choice of antibiotics and
projected duration based on diagnosis and clinical
evaluation
• Confirm duration at re-evaluation
• Automatic stop orders
• ? Pharmacy restrictions for courses >7d
Empirical therapy
Re-evaluation
1. Discontinue unnecessary and
‘companion’ antibiotics
2. Narrow the spectrum
3. Define and document projected
duration
Discontinue as projected if no new
relevant information
Clinical
course Microbiology
Day 0
Day 2-3
Day 7
Empirical therapy
Re-evaluation
1. Discontinue unnecessary and
‘companion’ antibiotics
2. Narrow the spectrum
3. Define and document projected
duration
Discontinue as projected if no new
relevant information
Clinical
course Microbiology
Day 0
Day 2-3
Day 5
Conclusion
• Antibiotics are for infection
• Antibiotic de-escalation and duration are two important strategies to reduce antibiotic exposure
• Less is more!
• De-escalation valuable in all types of pneumonia
• Duration can be limited to 7 days for most patients who are improving
• Scores and biomarkers no additional value if course is limited to 7 days
