Title: Optimizing Antibiotic Use in the ICU A Practical Approach to Antimicrobial Stewardship
1Optimizing 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
2Some 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
3Antimicrobial 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.
4Importance 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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8Discovery of New Antibiotic Classes
9Novel Antibiotic Development
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12Geographic Distribution of KPC Producers in USA
13ESKAPE 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.
14Clostridium Dificile
- Poor Hand Hygiene
- Mechanical scrub with soap and water
- Poor Environmental Cleanliness
- Indiscriminate use of antibiotics
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17What 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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19Stewardship Strategies in thePrescribing Workflow
20California 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.
21Economic 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
22General 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?
23DE-ESCALATIONDISCONTINUATIONSTOP WHEN YOU ARE
DONE!!
24Kaplan-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
25Antibiotic 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
26GENERAL UTI SUMMARY
- No need to treat
- Nitrites
- Bacteriuria other than pregnancy, transplant
- Treat UTI-gt 3 days
- Pyelonephritis -gt 2 weeks
27Biomarker 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
28PCT 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
29PCT Concentration Spectrum
30Duration 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
31Outcomes Procalcitonin in CAP
Christ-Crain M et al. Am J Resp Crit Care Med
2006 174 84-93
32PCT and SepsisLess Antibiotics, No Impact on
Survival
Bouadma L et al. Lancet 2010 375 463-474
33PCT 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
34Where 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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40Antibiotic 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
41Mindset of MDs What Influences Antibiotic
Prescribing?
42Conclusions
- 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