Transcript TIENAM

De-Escalation Therapy™ in Clinical Practice:
Delivery of Effective and Responsible
Antimicrobial Treatment Consensus III
Developed by Consensus III Medical Expert
Group
:
Gert Höffken,
Universitat Dresden, Dresden, Germany
George Karam, Louisiana State University Medical School, New Orleans, LA, USA
Marin Kollef, Washington University School of Medicine, St. Louis, MO, USA
Carlos Luna, University of Buenos Aires, Argentina
Johan Maertens, University Hospital Gasthuisberg, Leuven, Belgium
Michael Niederman, Winthrop University Hospital, Mineola, NY, USA
David Paterson, University of Pittsburgh Medical School, PA, USA
Jordi Rello, University Hospital Joan XXIII, Tarragona, Spain
Jean-Louis Trouillet, Groupe Hospitalier PITIE SALPETRIERE, Paris, France
De-Escalation Therapy and the pinwheel symbol are trademarks of Merck & Co., Inc., Whitehouse Station, NJ, USA.
TEN 2003-W-9415 SS
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An Art in Medicine
Balance
An Evidence-Based Problem:
A Theoretical Dilemma:
Mortality with
Inadequate Therapy
Concern of Resistance with
Broad-Spectrum Therapy
Clinical evidence showing lack of resistance with
heterogeneous use of broad-spectrum therapy
Evans RS et al. N Engl J Med 1998;338:232-238.
Gruson D et al. Am J Respir Crit Care Med 2000;162:837-843.
Raymond DP et al. Crit Care Med 2001;29:1101-1108.
Copyright © 2003 Merck & Co., Inc., Whitehouse Station, NJ, USA.
All rights reserved. 2-04 TEN 2002-W-9397-SS
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High Mortality with HAP and
Severe Sepsis
• Included among the most frequent serious infections in the ICU are:
– Hospital-acquired pneumonia (HAP)
– Severe sepsis.
– HAP and severe sepsis are associated with high mortality rates.
• Inadequate therapy for HAP and severe sepsis increases mortality.
Kollef MH. Clin Infect Dis 2000;31(Suppl 4):S131-S138.
Richards MJ et al. Crit Care Med 1999;27:887-892.
Ibrahim EH et al. Chest 2000;118:146-155.
Van der Poll T. Lancet Infect Dis 2001;1:165-174.
Bernard GR et al. N Engl J Med 2001;344:699-709.
Alvarez-Lerma F et al. Intensive Care Med 1996;22:387-394.
Pfaller MA et al. Antimicrob Agents Chemother 2000;44:747-751.
Garnacho-Montero J et al. Crit Care Med 2003;31:2742-2751.
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Mortality* Associated with Initial Inadequate Therapy
in Critically Ill ICU Patients with HAP or Sepsis
Alvarez-Lerma, 1996**
16.2%
24.7%
38%
Luna, 1997
Rello, 1997
91%
15.6%
37%
Initial inadequate
therapy
33.3%
Kollef, 1998
60.8%
Ibrahim, 2000***
28.4%
Harbarth, 2003***
24%
Valles, 2003***
31%
0%
Initial adequate
therapy
61.9%
39%
63%
20%
Mortality
40%
60%
*Mortality refers to crude or infection-related mortality. **Includes patients with HAP.
***Patients had blood stream infections rather than pneumonia as in the other studies.
Alvarez-Lerma F et al. Intensive Care Med 1996;22:387-394.
Luna CM et al. Chest 1997;111:676-685.
Rello J et al. Am J Respir Crit Care Med 1997;156:196-200.
Kollef MH et al. Chest 1998;113:412-420.
Ibrahim EH at al. Chest 2000;118:146-155.
Harbarth S et al. Am J Med 2003;115:529-535.
Valles J et al. Chest 2003;123:1615-1624.
80%
100%
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Defining Inadequate Therapy
• Inadequate therapy
– “. . .the microbiological documentation of infection…that was not
effectively treated at the time the causative microorganism and its
antibiotic susceptibility were known…”1
• Other factors to consider in defining Inadequate therapy:1,2
– Microbiologic data (including lack of consistently predicting outcome
based on in vitro susceptibility)
– Monotherapy versus combination therapy
– Dose and dosing frequency
– Penetration
– Timing
– Toxicity
– Risk of influencing resistance
– Prior antibiotic use
1. Kollef MH. Clin Infect Dis 2000;31(Suppl 4):S131-S138.
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2. Kollef MH et al. Chest 1999;115:462-474.
Delayed Therapy May Be Inadequate Therapy:
Results from a Single-Center Study in VAP
• Early appropriate therapy, before bacteriologic data
are known, leads to an improved outcome.
p<0.01
% Mortality
100
p=NS
91%
80
Adequate ATB therapy
71%
60
70%
Inadequate ATB therapy
40
38%
20
0
Pre-BAL (n=68)
Post-BAL (n=65)
ATB = antibiotic; BAL = bronchoalveolar lavage
Adapted from Luna CM et al. Chest 1997;111:676-685.
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De-Escalation Therapy™
Stage 1
• Administering broad-spectrum antibiotic therapy to
improve outcomes (decrease mortality, prevent
organ dysfunction, and decrease length
of hospital stay)
Stage 2
• Focusing on de-escalating as a means to minimize
resistance and improve cost-effectiveness
Note: In some patients, additional therapy to include
pathogens not covered with the initial regimen may be necessary.
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Patients Who May Benefit from Empirical
Broad-Spectrum Antimicrobial Therapy
Critically ill patients with serious infections, for
example, patients with:
• HAP
• VAP
• Bacteremia
• Severe sepsis (including bacterial and fungal
pathogens)
• Severe community-acquired pneumonia
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TIENAM
Unsurpassed Experience and Time-Tested Reliability
Consider imipenem your carbapenem of choice for patients
with serious nosocomial infections:
• Broad & Balance-spectrum activity
• Reliable efficacy
• Low potential for resistance/cross-resistance
• Favorable pK/pD
• Low endotoxin release
• Time-tested tolerability
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