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WCACS, Antwerp, March 2007
Preventie van Antibioticaresistentie
Stijn BLOT, PhD Afdeling voor Intensieve
Zorg Universitair Ziekenhuis Gent
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• Infections in the ICU emergence of antibiotic
  resistance.

NNIS system, Dec. 1999
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Excessive use of antibiotics
Selecting proces
Antibiotic resistance
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Determinants of resistance
Bonten M. Intensive Care Med 2003 29 1-2.
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Antimicrobial Resistance Key Prevention
Strategies
Pathogen
Susceptible Pathogen
Resistant Pathogen
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12 Steps to Prevent Antimicrobial Resistance

• 1. Vaccinate
• Get the catheters out
• Target the pathogen
• Access the experts
• 5. Practice antimicrobial control
• 6. Use local data
• 7. Treat infection, not contamination
• 8. Treat infection, not colonization
• 9. Save your last line antibiotics
• Stop treatment when infection is cured or
  unlikely
• 11. Isolate the pathogen
• 12. Break the chain of contagion

Prevent Infection
Diagnose and Treat Infection Effectively
Use Antimicrobials Wisely
Prevent Transmission
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Prevent Infection Step 1 Vaccinate
Fact Pre-discharge influenza and pneumococcal
vaccination of at-risk hospital patients and
influenza vaccination of healthcare personnel
will prevent infections.

• Actions
• - give influenza / pneumococcal vaccine to
  at-risk patients before discharge
• - get influenza vaccine annually

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Prevent Infection Step 2 Get the catheters out
Fact Catheters and other invasive devices are
the 1 exogenous cause of hospital-onset
infections.
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Preventive measures for catheter-related
bloodstream infection
Review of risk factors for CR-BSI caused by CVCs
based on prospective studies using multivariate
analysis or RCT of a preventive measure.
Measures that significantly reduced risk -
Formal training in CVC placement and care - Use
of maximal sterile barrieres at insertion -
Chlorexidine vs. Povidone-iodine - Topical
antiinfective ointment or dressing - Catheters
with an antiinfective surface

• Safdar N, et al. Medicine 2002 81 466-79.

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Prevention works!
Impact of a prevention strategy targeted at a
vascular-access care on incidence of infections
acquired in ICUs.
/1000 patient days
Implemetation slide show in-service
individual training.

• Eggiman P, et al. Lancet 2000 355 1864-8.

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Prevention works!
Eliminating CR-BSI in the ICU
Multifaceted intervention program

• Berenholtz S, et al. Crit Care Med 2004 32
  2014-20.

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Diagnose Treat Infection Effectively Step 3
Target the pathogen

• FactAppropriate antimicrobial therapy (correct
  regimen, timing, dosage, route, and duration)
  saves lives.

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• Importance of appropriate antimicrobial therapy!
• Significant reduction in mortality if
• - appropriate therapy
• - no or short delay in the initiation of the
  therapy

Kollef et al. Chest 1999 115 462-74. Ibrahim et
al. Chest 2000 118 146-55.
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• (!) Infections caused by antibiotic resistant
  microorganisms are more often treated
  inappropriately.

Ibrahim et al. Chest 2000 118 146-55.
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Dead bugs dont mutate!

• Grootste fout
• Te laag geconcentreerde AB
• voor een te lange periode.

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PK/PD parameters affecting antibiotic efficacy in
vivo
Concentration
CmaxMIC
AUCMIC
MIC
TgtMIC
PAE
0
Time (hours)
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Probability of developing resistance
Probability of remaining susceptible ()
Thomas et al. Antimicrob Agents Chemother
199842521527
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PK/PD parameters affecting antibiotic efficacy in
vivo
Concentration
CmaxMIC
AUCMIC
MIC igv. resistentie
MIC
TgtMIC
PAE
0
Time (hours)
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Diagnose Treat Infection effectively Step 4
Access the experts

• Fact Infectious diseases expert input improves
  the outcome of serious infections.
• consult infectious diseases experts about
  patients with serious infections

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Achieving fast and appropriate antimicrobial
therapy
Blot Vandewoude. Acta Clin Belg 2004.
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Bacteremia caused by gram-neg. bacteria
In-hospital mortality AB-S (n208)
41.8 AB-R (n120) 45.0 (P0.58)
? No difference in mortality
Blot S, et al. Clin Infect Dis 2002 34 1600-6.
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• ANTIMICROBIAL THERAPY Gram-negative bacteremia

No difference in therapy ? no difference in
outcome.
Blot S, et al. Clin Infect Dis 2002 34 1600-6.
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Acinetobacter bacteremia in ICU patients Empiric
adequate therapy (lt48h) 85!
In-hospital mortality Cases 42.2 Controls
34.4 (P0.38) ? attributable
mortality 7.8 (95 CI -10 25)
Blot S, et al. Intens Care Med 2003
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Attributable mortality of MRSA bacteremia in
critically ill patients - A matched cohort study
In-hospital mortality MRSA (n47)
63.8 Controls (n94) 40.4 (P0.02) ?
attributable mortality 23.4 (95 CI 7
40)
Blot S, et al. Arch Intern Med 2002 162 2229-35.
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Use Antimicrobials Wisely Step 5 Practice
antimicrobial control

• Fact
• Programs to improve antimicrobial use are
  effective.
• Action
• Engage in local antimicrobial use quality
  improvement efforts

Schiff GD, et al. Jt Comm J Qual Improv
200127387-402
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Use Antimicrobials Wisely Step 6 Use local data

• Fact The prevalence of resistance can vary by
  time, locale, patient population, hospital unit,
  and length of stay.

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Prevalence of Fluoroquinolone-Resistant
Escherichia coli Variability among Patient
Populations
Percent Resistant Patient-isolates
Patient Characteristics
San Francisco General Hospital 1996-1997
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Use Antimicrobials Wisely Step 6 Use local data

• Fact
• The prevalence of resistance can vary by local
  patient population, hospital unit, and length of
  stay.
• Actions
• know your local antibiogram
• know your patient population

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Use Antimicrobials Wisely Step 7 Treat
infection, not contamination

• Fact A major cause of antimicrobial overuse is
  treatment of contaminated cultures.
• Actions
• use proper antisepsis for blood other cultures
• culture the blood, not the skin or catheter hub
• use proper methods to obtain process all
  cultures

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Use Antimicrobials WiselyStep 8 Treat
infection, not colonization

• Fact A major cause of antimicrobial overuse is
  treatment of colonization.
• Actions
• treat pneumonia, not the tracheal aspirate
• treat bacteremia, not the catheter tip or hub
• treat urinary tract infection, not the indwelling
  catheter

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Use Antimicrobials WiselyStep 9 Save your last
line antibiotics

• Fact overuse of glycopeptides/ carbapenems
  promotes emergence, selection, and spread of
  resistant pathogens.
• Actions
• treat infection, not contaminants or colonization
• use carbapenems only when necessary
• fever in a patient with an intravenous catheter
  is not a routine indication for vancomycin

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Use Antimicrobials Wisely Step 10 Stop
antimicrobial treatment

• Fact Failure to stop unnecessary antimicrobial
  treatment contributes to overuse and resistance.
• Actions
• when infection is cured
• when cultures are negative and infection is
  unlikely
• when infection is not diagnosed

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Comparison of 8 vs 15 days of antibiotic therapy
for ventilator-associated pneumonia in adults.
Difference in - antibiotic-free days No
difference in - mortality - organ
failure-free days - mechanical ventilation
days - ICU stay - infection recurrence rate
More AB-resistance in 15-days group!! (42 vs.
62 P0.04)
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Prevent Transmission Step 11 Isolate the
pathogen

• Fact Patient-to-patient spread of pathogens can
  be prevented.
• Actions
• use standard infection control precautions
• contain infectious body fluids
• (use approved airborne/droplet/contact isolation
  precautions)
• when in doubt, consult infection control experts

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Prevent Transmission Step 12 Contain your
contagion

• Fact Healthcare personnel can spread
  antimicrobial-resistant pathogens from
  patient-to-patient.

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Effect of Hand Hygiene on Resistant Organisms

• Year Author Setting Impact on organisms
• 1982 Maki adult ICU decreased
• 1984 Massanari adult ICU decreased
• 1990 Simmons adult ICU no effect
• 1992 Doebbeling adult ICU decreased with one
  versus another hand hygiene product
• 1994 Webster NICU MRSA eliminated
• 1999 Pittet hospital MRSA decreased

Pittet D. Emerg Infect Dis 20017234-240
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Prevent Transmission Step 12 Break the chain of
contagion

• Fact Healthcare personnel can spread
  antimicrobial-resistant pathogens from patient to
  patient.
• Actions
• stay home when you are sick
• contain your contagion
• keep your hands clean

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12 Steps to Prevent Antimicrobial Resistance
Clinicians hold the solution Take steps NOW to
prevent antimicrobial resistance!
12 Contain your contagion 11
Isolate the pathogen 10 Stop
treatment when cured 9 Know when to
say no to vanco 8 Treat infection, not
colonization 7 Treat infection, not
contamination 6 Access the
experts 5 Use local data 4
Practice antimicrobial control 3 Target the
pathogen 2 Get the catheters out
1 Vaccinate
Prevent Transmission Use Antimicrobials
Wisely Diagnose Treat Effectively Prevent
Infections
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Dank u