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Optimizing Antibiotic Use in the ICU A Practical Approach to Antimicrobial Stewardship

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Title: Optimizing Antibiotic Use in the ICU A Practical Approach to Antimicrobial Stewardship


1
Optimizing Antibiotic Use in the ICUA
Practical Approach to Antimicrobial Stewardship
  • George Sakoulas, MD
  • UCSD School of Medicine
  • Sharp Memorial Hospital, San Diego, CA
  • July 2013

2
Some Points to Consider
  • The antibiotic era is 4.5 billion years old
  • Resistance to antibiotics exists in nature before
    medicine actually discovers or uses them
  • Unlike any other class of medication, antibiotics
    treat not only the individual, but have societal
    impacts
  • 70 of antibiotics in USA go to
  • Animal Husbandry

3
Antimicrobial Treatment Considerations
  • Must be timely delay in initiation potentially
    lethal
  • Appropriate must cover the offending pathogen(s)
  • Administered at adequate dose and intervals
    consistent with pK/pD parameters
  • Timely streamlining based on clinical response
    and microbiological data
  • Prompt discontinuation when practical

Deresinski S. Clin Infect Dis 2007
45S177-S183 Allerberger F et al. Clin Microbiol
Infect 2008 14 197-199.
4
Importance of Initial, Appropriate Antibiotic
Therapy
selection of initial appropriate antibiotic
therapy (ie, getting the antibiotic treatment
right the first time) is an important aspect of
care for hospitalized patients with serious
infections. ATS/IDSA Guidelines
A Study by Kollef and Colleagues Evaluating the
Impact of Inadequate Antimicrobial Therapy on
Mortality
60
52
Plt.001
50
42
40
Hospital Mortality ()
30
24
18
20
10
0
All-Cause Mortality
Infection-Related Mortality
Inadequate antimicrobial treatment (n169)

Adequate antimicrobial treatment (n486)

ATSAmerican Thoracic Society IDSAInfectious
Diseases Society of America.
Adapted from Kollef MH et al. Chest.
1999115462-474. ATS/IDSA. Am J Respir Crit Care
Med. 2005171388-416.
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Discovery of New Antibiotic Classes
9
Novel Antibiotic Development
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Geographic Distribution of KPC Producers in USA
13
ESKAPE and Mortality in Bacteremia
  • VRE (n683) vs VSE (n931) OR 2.52
    (1.9-3.4) Ref 1
  • MRSA (n382) vs MSSA (n433) 11.8 vs 5.1 (plt
    0.001) Ref 2
  • Klebsiella pneumoniae 52 vs. 29
    (p0.007) Ref 3
  • ESBL (n48) vs non-ESBL (n99)
  • Acinetobacter baumanii 58 vs. 28 (plt 0.05)
    Ref 4
  • Imipenam R (n40) vs S (n40)
  • Pseudomonas aeruginosa 21 vs. 12 (p0.08) Ref
    5
  • MDR (n82) vs non-MDR (n82)
  • REFERENCES
  • Diaz-Granados et al. Clin Infect Dis 200541
    327-333.
  • Melzer M et al. Clin Infect Dis 2003 37
    1453-1460.
  • Tumbarello M et al. Antimicrob Agents Chemother
    2006 50 498-504.
  • Kwon K et al. J Antimicrob Chemother 2007 59
    525-530.
  • Aloush V et al. Antimicrob Agents Chemother 2006
    50 43-48.

14
Clostridium Dificile
  • Poor Hand Hygiene
  • Mechanical scrub with soap and water
  • Poor Environmental Cleanliness
  • Indiscriminate use of antibiotics

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What is Antimicrobial Stewardship?
  • Systematic approach to optimize clinical outcomes
    while minimizing consequence of antibiotic use
  • Toxicity
  • Selection of resistance
  • Selection of virulent organisms
  • Clostridium dificile
  • Combine with comprehensive infection control to
    limit emergence and transmission of resistance
  • Reduce healthcare costs without adversely
    impacting care
  • Bottom line-STREAMLINE therapy

Dellit T et al. Clin Infect Dis 2007 44 159-177
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Stewardship Strategies in thePrescribing Workflow
20
California SB 739-HAI Initiative Control and
report healthcare-acquired infections (eg.
Central line insertion practice) Antibiotic
stewardship included By January 1, 2008, CDPH
shall take all of the following actions to
protect against health care associated infections
(HAI) in general acute care hospitals
statewide Require that general acute care
hospitals develop a process for evaluating the
judicious use of antibiotics, the results of
which shall be monitored jointly by appropriate
representatives and committees involved in
quality improvement activities.
21
Economic Considerations for Antibiotic Stewardship
  • Antibiotic use restriction and costs should not
    be the only focus
  • Antibiotic costs are a small percentage of
    treatment costs
  • Costs from hospital length of stay, total
    hospital costs, and infection prevention should
    be considered
  • Return to productivity

22
General Antimicrobial Prescribing Principles
  • Day 1 Empiric Antibiotics
  • Need rapid diagnotics
  • Mixing vs. Cycling
  • Day 3 DE-ESCALATION
  • What antibiotics are being prescribed?
  • What do the cultures show?
  • Is there infection?
  • LEUKOCYTOSIS INFECTION
  • Fever is not necessarily due to infection
  • What is the clinical picture?

23
DE-ESCALATIONDISCONTINUATIONSTOP WHEN YOU ARE
DONE!!
24
Kaplan-Meier Estimates of the Probability of
Survival Probability of survival is for the 60
days after ventilator-assisted pneumonia onset as
a function of the duration of antibiotics
No excess mortality No more recurrent
infections More antibiotic-free days
Chastre, J. et al. JAMA 20032902588-2598
25
Antibiotic SinkThe UTI
  • UTI requires at least 1 of the following
  • Pyuria (gt10 WBC/hpf)
  • Symptoms (dysuria, hematuria, urgency)
  • BACTERIURIA IS NOT A UTI
  • QUANTITATIVE BACTERIURIA (CFU/ML) IS IRRELEVANT
  • The Only Patients in whom bacteriuria requires
    therapy
  • Pregnancy
  • Renal transplant patients
  • Pre-op Patient

26
GENERAL UTI SUMMARY
  • No need to treat
  • Nitrites
  • Bacteriuria other than pregnancy, transplant
  • Treat UTI-gt 3 days
  • Pyelonephritis -gt 2 weeks

27
Biomarker Procalcitonin (PCT)
  • 116 amino acid peptide, MW 13 kD product of
    CALC-I gene
  • PCT is normally produced, enzymatically processed
    into calcitonin, and stored in granules in the
    neuroendocrine C cells of the thyroid
  • Serum concentrations of PCT lt 0.5 ng/mL
  • Under condition of infection, PCT is produced
    constitutively by all cells
  • Direct toxins or LPS
  • Indirect stimualtion by pro-inflammatory
    cytokines IL-b, IL-6, TNF-a
  • Serum concentrations up to 2000X increase
  • First described to be elevated in staphylococcal
    TSS in 1983
  • Subsequently considered a potential parameter of
    infection in 1993

28
PCT Kinetics
  • Procalcitonin (PCT) increases after 2-3 hours
    after induction e.g. by endotoxin
  • May increase to levels up to several hundred
    nanogram per ml in severe sepsis and septic
    shock.
  • After successful treatment intervention the
    procalcitonin value decreases, indicating a
    positive prognosis
  • Persistingly high or even further increasing
    levels are indicators for poor prognosis.
  • Levels then rise rapidly, reaching a plateau
    after 6-12 hours.
  • PCT concentrations remain high for up to 48
    hours, falling to their baseline values within
    the following 2 days. The half-life is about 20
    to 24 hours.

Brunkhorst F.M. et al., Intens Care Med 1998, 24
888-892
29
PCT Concentration Spectrum
30
Duration of Antibiotics for CAP
Christ-Crain M et al. Am J Respir Crit Care Med.
2006 Apr 7 Christ-Crain M Müller B, Swiss Med
Wkly 2005, 135 451-460
31
Outcomes Procalcitonin in CAP
Christ-Crain M et al. Am J Resp Crit Care Med
2006 174 84-93
32
PCT and SepsisLess Antibiotics, No Impact on
Survival
Bouadma L et al. Lancet 2010 375 463-474
33
PCT DOES NOT Replace Routine Microbiology Or
Clinical Judgment
  • PCT may not elevated in some bloodstream
    infections
  • S. aureus bacteremia
  • Enterococcus bacteremia
  • Subacute bacterial endocarditis
  • Candidemia

34
Where Else Are Molecular Rapid Diagnostics Needed
and Used?
  • Screening for resistant pathogens
  • RAPID Organism identification in sterile body
    fluids
  • Fastidious organisms
  • Prior antibiotics negate cultures
  • RAPID Susceptibility report
  • Risk Stratification of Patients
  • More expensive more potent antibiotics perhaps
    for the sicker patients

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Antibiotic Stewardship Must Coincide with
Infection Control/Prevention
  • Prevention
  • Optimal management of vascular and urinary
    catheters
  • Prevention of LRTI
  • Control
  • Hand hygiene
  • Contact precautions
  • Active surveillance
  • Education
  • Environmental cleaning
  • Improved communication between facilities

www.cdc.gov
41
Mindset of MDs What Influences Antibiotic
Prescribing?
42
Conclusions
  • Physicians needs better tools on how to initiate
    and stop antibiotics
  • Diagnostics
  • Education
  • Support systems
  • Stewardship teams are just one step to regulate
    antibiotic prescribing
  • The attitude of prescribing antimicrobials must
    switch from one of a right to one of a privilege
  • Erase the potential benefitgtgt potential harm
    mindset of prescribing antibiotics
  • De-escalate to narrower agents ASAP
  • Cut duration of antibiotics
  • Early stop for non-infections
  • Short high dose course in cases of infection
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