Transcript Antibiotic Stewardship in the ICU

Optimizing Antibiotic Use
in the ICU
A Practical Approach to Antimicrobial Stewardship
George Sakoulas, MD
UCSD School of Medicine
Sharp Memorial Hospital, San Diego, CA
July 2013
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
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; 45:S177-S183
Allerberger F et al. Clin Microbiol Infect 2008; 14: 197-199.
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
Hospital Mortality (%)
60
*P<.001
52*
50
42*
40
30
24
18
20
10
0
All-Cause Mortality
Inadequate antimicrobial treatment
(n=169)
ATS=American Thoracic Society; IDSA=Infectious Diseases Society of America.
Adapted from Kollef MH et al. Chest. 1999;115:462-474.
ATS/IDSA. Am J Respir Crit Care Med. 2005;171:388-416.
Infection-Related Mortality
Adequate antimicrobial treatment
(n=486)
Discovery of New Antibiotic Classes
Novel Antibiotic Development
Geographic Distribution of KPC
Producers in USA
ESKAPE and Mortality in Bacteremia
• VRE (n=683) vs VSE (n=931)
• MRSA (n=382) vs MSSA (n=433)
• Klebsiella pneumoniae
OR 2.52 (1.9-3.4)
Ref 1
11.8% vs 5.1% (p< 0.001) Ref 2
52% vs. 29% (p=0.007)
Ref 3
– ESBL (n=48) vs non-ESBL (n=99)
• Acinetobacter baumanii
58% vs. 28% (p< 0.05)
Ref 4
21% vs. 12% (p=0.08)
Ref 5
– Imipenam R (n=40) vs S (n=40)
• Pseudomonas aeruginosa
– MDR (n=82) vs non-MDR (n=82)
REFERENCES
1. Diaz-Granados et al. Clin Infect Dis 2005;41: 327-333.
2. Melzer M et al. Clin Infect Dis 2003; 37: 1453-1460.
3. Tumbarello M et al. Antimicrob Agents Chemother 2006; 50: 498-504.
4. Kwon K et al. J Antimicrob Chemother 2007; 59: 525-530.
5. Aloush V et al. Antimicrob Agents Chemother 2006; 50: 43-48.
Clostridium Dificile
• Poor Hand Hygiene
– Mechanical scrub with soap and water
• Poor Environmental Cleanliness
• Indiscriminate use of antibiotics
What is Antimicrobial Stewardship?
• Systematic approach to optimize clinical outcomes
while minimizing consequence of antibiotic use
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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
9
Stewardship Strategies in the
Prescribing Workflow
ASP Strategies
Patient Evaluation
• Education/Guideline
Choice of Antimicrobial
• Formulary Restriction
and Pre-authorization
Prescription Ordering
• Computer-assisted
strategies
Dispensing Antimicrobial
• Review and Feedback
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.”
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
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?
DE-ESCALATION
DISCONTINUATION
STOP WHEN YOU ARE DONE!!
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 2003;290:2588-2598
Antibiotic “Sink”
The “UTI”
• UTI requires at least 1 of the following
– Pyuria (>10 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
GENERAL UTI SUMMARY
• No need to treat
– Nitrites
– Bacteriuria other than pregnancy, transplant
• Treat UTI-> 3 days
• Pyelonephritis -> 2 weeks
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 < 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
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
PCT Concentration Spectrum
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
Outcomes: Procalcitonin in CAP
Christ-Crain M et al. Am J Resp Crit Care Med 2006; 174: 84-93
PCT and Sepsis:
Less Antibiotics, No Impact on Survival
Bouadma L et al. Lancet 2010; 375: 463-474
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
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
Antibiotic Stewardship Must Coincide
with Infection Control/Prevention
• Prevention
– Optimal management of vascular and urinary
catheters
– Prevention of LRTI
• Control
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Hand hygiene
Contact precautions
Active surveillance
Education
Environmental cleaning
Improved communication between facilities
www.cdc.gov
Mindset of MD’s: What Influences
Antibiotic Prescribing?
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 benefit>> 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