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Pneumonies acquises sous VM .pdf



Nom original: Pneumonies acquises sous VM.pdf
Titre: Topo-DURPI 2009-J.Chastre
Auteur: G-BCH-MWOLFF

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Pneumonies acquises sous VM:
Conduite du traitement antibiotique
Jean Chastre

Pneumonies acquises sous VM:
Conduite du traitement antibiotique
5 questions essentielles
1. Quand faut-il commencer le traitement?
2. Par quelle antibiothérapie?
3. Comment optimiser le traitement une
fois le germe identifié?
4. Quand faut-il utiliser les antibiotiques
en association?
5. Combien de temps faut-il traiter?

What is the optimal time to
start therapy?
As soon as possible, at
least in patients with true
VAP.

Duration of hypotension before initiation of
effective antimicrobial therapy and survival in 2154
patients with septic shock
Kumar et al. CCM 2006

What is the optimal time to
start therapy?
The need to immediately start a new
antimicrobial treatment in patients with
true VAP should not lead to
indiscriminate use of antibiotics in the
ICU.

Campaign to Prevent Antimicrobial Resistance in Healthcare Settings

xx

Selection for antimicrobial-resistant Strains

x
x

Resistant Strains
Rare
x
x

Antimicrobial
Exposure

xx

x
x

xx

Resistant Strains
Dominant

Fluoroquinolone Use and Resistance Rates
in P. aeruginosa and Gram-negative Bacilli

35

250

30

200

25
20

150

15

100

10
5

GNB
P. aeruginosa
Fluoroquinolone use

0

50
0

90-93 1994 1995 1996 1997 1998 1999 2000

Fluoroquinolone use, kg x103

Strains resistant to ciprofloxacin, %

Neuhauser et al. JAMA 2003;289:885-8

Pneumonies acquises sous VM:
Conduite du traitement antibiotique
Questions essentielles
1. Quand faut-il commencer le traitement?
– Après réalisation des prélèvements
microbiologiques
– Dans le cadre d’un protocole explicite
comportant
– un examen direct des sécrétions
respiratoires
– des cultures au moins semiquantitatives
– une ré-évaluation à J2-J3

HAP, VAP or HCAP Suspected
1
2

3

Obtain Lower Respiratory Tract (LRT) Sample for Culture
(Quantitative or Semi-quantitative) & Microscopy
Unless There Is Both A Low Clinical Suspicion for Pneumonia & Negative
Microscopy of LRT Sample, Begin Empiric Antimicrobial Therapy Using
Algorithm in Figure 2 & Local Microbiologic Data

Days 2 & 3: Check Cultures & Assess Clinical Response:
(Temperature, WBC, Chest X-ray, Oxygenation, Purulent Sputum,
Hemodynamic Changes & Organ Function)

Clinical Improvement at 48 -72 Hours
NO
Cultures Search for Other
Pathogens,
Complications , Other
Diagnoses or Other
Sites of Infection

YES
Cultures +
Adjust Antibiotic Therapy,
Search for Other
Pathogens,
Complications,Other
Diagnoses or Other
Sites of Infection

Cultures -

Consider
Stopping
Antibiotics

Cultures +

De-escalate Antibiotics,
if Possible.
Treat Selected Patients
for 7- 8 Days
& Reassess

Diagnostic Consequences of FOB Timing With
Regard to Previous Antimicrobial Therapy

A
Antimicrobial agents

B
Antimicrobial agents

Fiberoptic
bronchoscopy

Fiberoptic
New bronchoscopy
ABs
Days of MV

Evolution of microbial isolates grown in
significant concentrations during the first 72 h
of antibiotic treatment in 35 pts with VAP
Prats et al. Eur Respir J 2002
No. of isolates recovered in significant concentrations
80
60

66

40

34
23

20

9
2

0
PSB1
0h

PSB2
12 h

PSB3
24 h

PSB4
48 h

PSB5
72 h

The Quantitative Strategy: First Step

No further
investigation/
observe

NO

Clinical features
suggest infection?

YES

Immediate sampling of distal
airways by bronchoscopy with
BAL/PSB
before introduction of new ABs

Usefulness of BAL Cells Microscopic
Examination for Diagnosing VAP
Chastre et al. Am J Med 1988;85:499-506

Usefulness of BAL Cells Microscopic
Examination for Excluding VAP
Chastre et al. Am J Med 1988;85:499-506

The “Quantitative” Strategy: Deciding
Whether or not to Treat with New ABs
Observe,
look for another
infection(s)

Direct specimen
examination

NO
Positive
quantitative
cultures
YES
Start antibiotics
based on
culture results

Observe;
look for another
infection(s)

NO

Signs of
severe
sepsis
YES

NO

Bacteria
present
YES

Start antibiotics immediately using
Gram stain results, ATS/IDSA guidelines,
And local epidemiology

Brun-Buisson, C. et al.
Chest 2005

The “Clinical”
Strategy

Clinical features
suggesting VAP
YES

Obtain immediate bronchial aspirates
and blood cultures before
starting or changing existing antibiotics
Start empiric antibiotics immediately based on risk factors,
time of onset & local epidemiology of MDR pathogens
Using ATS guidelines

Positive
cultures

NO

YES

Adjust antibiotics
based on culture results
& clinical response

Stop antibiotics if
low clinical probability and
no signs of severe sepsis

The “Clinical” VAP Strategy:
Torres and Ewig NEJM 2004;350: 433-5

Step 2: Re-evaluation at 48-72 hr
Discontinuation of antimicrobial treatment if and
only if the 3 following criteria fulfilled:
–Clinical diagnosis of VAP unlikely (there are
no definite infiltrates on chest x-rays and two
of the 3 clinical criteria are absent) or
alternative (noninfectious) diagnosis
confirmed
–Culture results nonsignificant
–No severe sepsis or shock.

The “Quantitative” Strategy: Deciding
Whether or not to Treat with New ABs
Direct specimen
examination

Observe;
NO
look for another
infection(s)

Signs of
severe
sepsis

NO

Bacteria
present
YES

YES
Start antibiotics
immediately using
ATS/IDSA guidelines

Start antibiotics
immediately using
direct specimen
examination results
and local epidemiology

Causes of Fever and Pulmonary Densities in
Patients with Clinical Manifestations of VAP
45 pts
with a definitive
source of fever

50 pts
completed the study

37
infectious

19
pneumonia

14
concomitant
infections

14
sinusitis
cath. related inf.
UTI
11
concomitant
infections

Meduri et al. Chest 1994

8 noninfectious

candidemia
cholecystitis
empyema
peritonitis
0
concomitant
infections

6
pulmonary

2
extrapulmonary

5 fibroproliferation
1 aspiration

1 pancreatitis
1 drug fever

Potential Advantages of the "Invasive"
Strategy for Diagnosing V-A-P
Search for alternative
explanations for respiratory
dysfunction and fever is greatly
facilitated in patients without true
pneumonia by the absence of
new antibiotics.

Inappropriate Use of Antibiotics and the Risk
for Delayed Admission and Masked or Missed
Diagnosis in 217 Patients with Infection
Liu et al. Arch Intern Med 2001
60%

*P<0.03
†P<0.001

50
40

34.8

30

*

20
10
0

Delayed admission
Masked or missed
diagnosis

48.7


21.6

*

25.5



With antimicrobial Without antimicrobial
activity in urine
activity in urine
n=115
n=102

Results of Trials Comparing an Invasive
Strategy with a Clinical Strategy
AUTHOR

TOTAL
NO. OF
PATIENTS

STUDY
DESIGN

Sanchez

51

Ruiz

62

Sole-Violan

88

Peery

58

Heyland

141

Fagon,
Chastre
Heyland, for
the CCCTG

413

Monocenter,
randomized
Monocenter,
randomized
Monocenter,
randomized
Monocenter,
randomized
Multicenter,
nonrand.
Multicenter,
randomized
Multicenter,
randomized

739

MORTALITY, %

P
VALUE

Invasive Clinical
46

26

NS

38

46

NS

22

21

NS

10

32

0.04

18

35

0.03

31

39

0.07

18.9

18.4

0.94

Actuarial 28-day Survival Among 413 Patients
Assigned to the Invasive or Clinical Strategy
Fagon, Chastre, Wolff, et al. Ann Intern Med 2000

Overall Survival, %

100

Invasive

80
60

Clinical
40
20

P=0.07

0
0

5

10

15

20

25

Days after Randomization

30

16
Teicoplanin

Vancomycin

Ciprofloxacin

Ofloxacin

Pefloxacin

Amikacin

Tobramycin

Netilmicin

Gentamicin

Imipenem

Piperacillin-tazobactam

Ceftazidime

Cefotaxime

P=0.02

P=0.04

P=0.01

P=0.007

P=0.03

P=0.009

P=0.04

P=0.03

P=0.02

P=0.10

P=0.006

P=0.04

P=0.02

P=0.006

28

Amoxicillin-clavulanate

Antibiotic-Free Days, n

Antibiotic Usage According to Diagnostic
Strategy
Fagon, Chastre, Wolff, et al. Ann Intern Med 2000

26

24

22

20

18

Clinical
Invasive

A Randomized Trial of Diagnostic
Techniques for VAP
The Canadian Critical Care Trials Group. N Engl J Med 2006

• 739 patients in 28 ICUs in Canada and US
with suspected VAP.
• Patients were randomized using a 2-by-2
factorial design:
– BAL with quantitative cultures vs standard endotracheal aspiration
with cultures
– Empirical combination therapy using meropenem plus ciprofloxacin
vs monotherapy with meropenem.

A Randomized Trial of Diagnostic Techniques
for VAP
The Canadian Critical Care Trials Group, N Engl J Med 2006
Outcome

Mortality, %

Endotracheal Bronchoalveolar
aspiration
lavage
(n=374)
(n=365)
18.4
18.9

P value
0.94

Duration of MV, d

8.9

8.8

0.31

ICU length of stay, d

12.3

12.2

0.22

Overall clinical
assessment
Cure, %
Clinical failure, %
Indeterminate, %

Antibiotic discontinuation
on Day 6, %
Targeted therapy on day
6, %

0.90
60.4
28.6
11.0
21.1

59.7
30.1
10.1
21.1

74.6

74.2

0.90

A Randomized Trial of Diagnostic Techniques
for VAP: Potential Limitations and Caveats
The Canadian Critical Care Trials Group, N Engl J Med 2006
Kollef M., Editorial, N Engl J Med 2006

The study population was restricted to patients
with a low probability of infection or colonization
with potentially antimicrobial-resistant bacteria.
A large fraction (29%) of patients had new
antibiotics initiated within 3 days before
randomization.
In many patients managed using BAL early deescalation was not performed, although clearly
indicated by microbiological results.

Characteristic

Fagon et al.
N=413
63

Heyland et al.
N=739
59

68

61

No. of days in ICU before
enrollment
APACHE II score

10.6

7.9

22

20.0

Organ dysfunction score at
day 1
Shock, %

7.4

5.6

37.5

22.2

30

12

15

8.8

Age, yr
Admission category
Medical, %

High-risk organisms
cultured*, %
Duration of MV after
inclusion, d

*P. aeruginosa, Acinetobacter spp., S. maltophilia, MRSA

Pneumonies acquises sous VM:
Conduite du traitement antibiotique
5 questions essentielles
1. Quand faut-il commencer le traitement?
2. Par quelle antibiothérapie?
3. Comment optimiser le traitement une
fois le germe identifié?
4. Quand faut-il utiliser les antibiotiques
en association?
5. Combien de temps faut-il traiter?

Empiric Antibiotics for HAP - 2004
ATS-IDSA Joined Guidelines

HAP, HCAP or VAP Suspected
(All Disease Severity)
Late Onset or Risk Factors for
Antibiotic -resistant (MDR) Bacteria

No

Yes

Limited Spectrum
Antibiotic Therapy

Broad Spectrum
Antibiotic Therapy
For MDR Pathogens

Starting Therapy Using Broadspectrum Drugs
Core Organisms Plus:
– P. aeruginosa
– Acinetobacter

Aminoglycoside or AntiPseudomonal Quinolone
(Ciprofloxacin, High Dose
Levofloxacin) Plus:
–Anti-pseudomonal cephalosporin
(ceftazidime; cefepime)
–Imipenem, meropenem, doripenem
–β-lactam/ β-lactamase inhibitor
(piperacillin/tazobactam)

Consider MRSA

± Linezolid or Vancomycin

How to select initial
antimicrobial therapy?







MRSA coverage needed in patients previously
identified as colonized or infected by this strain
and when local prevalence is high.
Use a regimen combining two antibiotics.
Take into account prior microbiologic results.
Do not use the same antibiotic class as already
received by the patient.
Do not use the same antibiotic class as already
received by other patients in the unit.

Staphylococcus aureus Methicillin
Resistance Rates, Pitié-Salpêtrière Hospital
(Courtesy Pr. Jarlier)
60
55

55.1

ICU
Surgery
Medicine

MRSA, %

50
45
40

38.7

35
30

28.4

33.1

25

22.8
21.9

20
15

1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005

Years

Trends in Percent MRSA and Incidence of S.
aureus Central Line-Associated Bloodstream
Infections in ICU
Burton, D. C. et al. JAMA 2009

P. aeruginosa VAP: Importance of Initial
Treatment Combining Two Effective
Antibiotics in 183 Episodes
Garnacho-Montero et al.CCM 2007

Appropriate initial
treatment, %
100
80
60

P <0.0001

Mortality, %
90

100
80

57

60

40

40

20

20

0

0
Monotherapy
(38/67)

Combination
(105/116)

P =0.09
51
37

Monotherapy
(34/67)

Combination
(43/116)

Operative Characteristics of Prior Microbiologic
Results According to the Potentially Drugresistant Microorganism Isolated Previously
Hayon et al. AJRCCM 2002
100%
80
60
40

84 85

86
79

66

82

87

62
MRSA
P. aeruginosa
A. baumannii

52

47
35

24

20
0
Sens.

Spec.

PPV

NPV

Early Antibiotic Treatment for VAP:
A Role for Routine Endotracheal
Aspirate (EA) Cultures Michel et al. Chest 2005

A total of 299 patients were studied
Of whom 41 developed VAP

Early Antibiotic Treatment for VAP:
A Role for Routine Endotracheal
Aspirate (EA) Cultures Michel et al. Chest 2005
• Among the 41 BAL specimens that were positive for VAP, EApre had identified the same microorganisms (with the same
antibiotic resistance patterns) in 34 cases (83%).
• Antibiotic treatment based on the results of the EA-pre was
adequate in 38 of the 40 assessable cases (95%).
• If the Trouillet-based strategy had been used, the antibiotic
treatment would have been adequate in 34 of the 41 cases
(83%; p 0.15 [vs EA-pre strategy]).
• Based on the ATS classification, the antibiotic treatment would
have been adequately prescribed in only 28 of the 41 cases
(68%; p 0.005 [vs EA-pre strategy]).

Crude Risk of Resistance to an Antibiotic
after Exposure to that same Antibiotic in 135
Episodes of P. aeruginosa VAP
Trouillet et al. CID 2002
57,1

Strain resistance, %

60

52,4

50

P<0.003

*

40

29

30
20

*
26

*

16,7
8,2

10
0
Imipenem

Ceftazidime

Ciprofloxacin

No prior exposure
Prior exposure

Effects of cycling and mixing on the selective conditions faced by a bacterial clone

Bergstrom, Carl T. et al. (2004) Proc. Natl. Acad. Sci. USA 101, 13285-13290

Copyright ©2004 by the National Academy of Sciences

Ventilator-associated pneumonia: Breaking the
vicious circle of antibiotic overuse
Marc Leone, et al. CCM 2007 Ahead of print

Pneumonies acquises sous VM:
Conduite du traitement antibiotique
5 questions essentielles
1. Quand faut-il commencer le traitement?
2. Par quelle antibiothérapie?
3. Comment optimiser le traitement une
fois le germe identifié?
4. Quand faut-il utiliser les antibiotiques
en association?
5. Combien de temps faut-il traiter?


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