Transcript IMR/VAP - Institut Maurice Rapin

Journée d’Infectiologie et Hygiène Hospitalière 2000
L’antibiothérapie peut-elle
prévenir les pneumopathies
nosocomiales?
Risque de Pneumopathie Nosocomiale et
Antibiothérapie
Ch Brun-Buisson
Antibiothérapie et Pneumonie nosocomiale
 L'antibiothérapie
peut-elle accroître le risque
– de pneumopathie chez les malades ventilés
– de pneumopathie à bactéries résistantes
 L'antibiothérapie
précoce peut-elle réduire le
risque de pneumopathie ultérieure
 pour ou contre l'antibiothérapie ?
Factors Associated with Nosocomial
Pneumonia
 Case-control
–
–
–
–
–
–
–
–
(unmatched) univariate analysis :
ICU(OR 12.5) > Surgical (OR2.4) >Medical
Chronic lung disease (OR 2.2), smoking (OR 1.7)
Prior antibiotics (OR 2)
Thoraco-abdominal surgery (OR 6.9)
Large volume aspiration (OR 12.5)
Nasogastric intubation (OR 6.6)
Endotracheal intubation :
long (OR 20.9) >short (OR 4.5)
Celis et al, Chest 1988
Factors Associated with Nosocomial
Pneumonia
Risk Factor
Adj OR 95% CI
P
Age >70 yrs
2.3
1.5-3.3
0.04
Chronic lung disease
3.7
2.6-5.3
0.0003
Depressed consciousness
5.8
3.6-9.3
0.0002
Endotracheal intubation
6.7
4.1-10.9 0.0001
Large volume aspiration
10.6
4.8-23
0.003
Thoraco-abd. surgery
4.7
2.9-7.5
0.0018
Celis et al, Chest 1988
Risk Factors for Nosocomial Pneumonia





114 / 5521 pts (1.9%) in Internal Medicine Dept of a
large tertiary care hospital
Case-matched study of 104 pairs
Controls "randomly" selected on same admission
period, and same underlying disease
Etiology considered when from bacteremia, pleural
fluid, serology, protected specimen via bronchoscopy,
or valid sputum specimen : 22 (21%) confirmed
Risk factors: Female sex, LOS >2 wks, previous
admission, and prior antibiotics
Gomez et al, E J C M I D, 1995
Antibiothérapie et Risque de Pneumopathie
3
ICUs ; 277 pts ventilés >24h
 Incidence VAP 15.5% (43 pts)
– Durée de ventilation moyenne 6.5 j
– 66% des cas < 5 j
Facteurs de Risque de VAP
Dysfonction viscérale >3 (aOR 10.2 [4.5-23])
 Age > 60 (aOR 5.1 [1.9-14.1])
 Position allongée (aOR 2.9 [1.3-6.8])
 Antibiotiques préalables (aOR 3.1 [1.4-6.9] )

Kollef, JAMA, 1993
EOP vs. LOP:
Epidemiology and Microbiology
 3,668
MICU/SICU pts
 420 Nosocomial pneumonia (NP)
– EOP: 235 (11.5%) at 2.1 +/- 1.2 d
– LOP: 185 (5%) at 9.9 +- 6.6
 Risk
factors :
– EOP: COPD, APACHE, Reintubation, Antacids,
vasopressors, H2-blockers
– LOP: Vasopressors, H2-blockers, Duration MV,
tracheostomy, CHF
Ibrahim et al, Chest 2000
Incidence & Risk Factors for VAP
(Cook & the CCCTG, Ann Intern Med, 1998)
16 ICUs (Can); 1014 patients
 Incidence pneumonia 144 (17.5%), mean (median) MV 9d (7d)
 Risk Factors for VAP *:


Intrinsic

Extrinsic
– Burns (RR 5.1)
– Paralytic agents (RR 1.6)
– Trauma (RR 5.0)
– H2-blockers (RR 1.2 [0.92-1.5]
– CNS disease (RR 3.4)
– Antibiotics (RR 0.37)
– Resp. dis. (RR 2.8)
– Cardiac dis. (RR 2.7)
– MV (RR 2.3)
– Aspiration (RR 3.25)
* Additional factors significant in univariate analysis: MODS,
Enteral nutrition, organ transplantation
Antibiothérapie préalable et risque de
Pneumopathie : Conclusion 1
L’antibiothérapie préalable pourrait être un
facteur de risque de survenue de VAP
 …mais les données sont discordantes

Prior Antibiotics and Etiology of Nosocomial
Pneumonia
Med/Surg
Wards
(n=83)
Readaptation/
Nursing homes
(n=148)
All cases
(n=231)
P
S.pneumoniae/
H. influenzae
6/33 (18%)
5/85 (6%)
9.5%
<0.05
GNB / mixed
GNB/GPC
17/30 (57%)
8/30 (27%)
42%*
<0.02
GPC
1/10 (10%)
2/12 (15%)
14%
ns
0/1
0/3
27/83 (33%)
20/148 (14%)
Proportion w.
Prior antibiotics
Others
Total
* p<0.01
Schleupner, ICHE 1992
ns
20%
0.01
Nosocomial Pneumonia: Prior antibiotics and
etiology
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Ventilator-Associated Pneumonia caused by
potentially drug-resistant bacteria
Trouillet et al, AJRCCM 1998; 157: 631-39



135 consecutive episodes of VAP studied with PSB/BAL
77 episodes caused by potentially AB-R bacteria
 MRSA, P.aeruginosa, A.baumannii, S.maltophilia
 Duration of MV before onset : 23  17; prior antibiotics : 96%
Compared to 58 episodes caused by other organisms
 duration of MV before onset : 9  2 ; prior antibiotics : 38%
Variables associated with isolation of resistant organisms
 Prior antibiotic use : OR 13.5 ([3.3-55] P=0.0003)
 Prior duration of MV >7d : OR 6 ([1.6-23] P=0.009)
 Broad-spectrum antibiotics : OR 4.1 ([1.2-14] P=0.025)
Ventilator-Associated Pneumonia caused by
potentially drug-resistant bacteria
Trouillet et al, AJRCCM 1998; 157: 631-39
MV <7d
AB - (n=22) AB + (n=12)
MV> 7d
AB – (n=17) AB+ (n=84)
Total bacteria
41
20
32
152
P.aeruginosa
0
4 (20%)
2 (6%)
33 (22%)
Acinetobacter,S.
maltophilia
0
1 (5%)
1 (3%)
26 (17%)
MRSA
0
1 (5%)
1 (3%)
30 (20%)
Total MR
morganisms
Enterobacteria
0
6 (30%)
4 (12%)
89 (59%)
10 (24%)
4 (20%)
28 (87%)
63 (41%)
S.pneumoniae
3 (7%)
0
0
0
Haemophilus
8 (19%)
2 (10%)
1
4 (3%)
MSSA
6 (15%)
0
7 (22%)
7 (5%)
Prognostic factors in ventilated patients with
nosocomial pneumonia
Variable
OR
P
Ultimately or rapidly
fatal Underlying disease
8.8
0.0018
Worsening ARF
12
0.01
Shock
2.8
0.016
Inappropriate Antibiotics
5.8
0.02
Torres et al, ARRD 1990
Risk factors for inadequate therapy

Prior antibiotics: OR 3.4 (2.9-4.2)
 Bloodstream infection: OR 1.9 (1.5-2.3)
 APACHE II(/pt): OR 1.04 (1.03-1.05)
 Decreasing age (/yr): OR 1.01 (1.01-1.02)
 (LRTI)
Risk of Mortality in patients treated
inadequately :
OR 4.2 (3.5-5.4)
Kollef et al., Chest 1999
Reasons for inadequate antibiotic therapy
Other cause
Non ICU-acq.
ICU-acquired
No Rx initiated
Candida not treated
Other GP
VRE untreated
MRSA untreated
EsPeniR GNB
ESB-Case GNB
0
Kollef et al., Chest 1999
5
10
15
20
25
30
% Causes of Inadequate Rx
35
40
Pathogènes à ‘Haut-risque’ & Mortalité des
VAP
Série
Pathogène
à Ht-risque
Mortalité (%)
Ht-risque Bas-risque
Celis
P.aeruginosa,
Enterobacteriacea, S.faecalis,
S.aureus, polymicrobial.
13/20 (65)
Kollef
P.aeruginosa, Acinetobacter,
X.maltophilia
27/36 (75) 21/67 (31)
Fagon
P.aeruginosa, Acinetobacter
Timsit
P.aeruginosa, Acinetobacter
~(87)
0
~(55)
16/19 (84) 18/37 (48)
Antibiothérapie et Risque de Pneumopathie
Conclusion 2
 L’antibiothérapie
préalable est associée :
– A des modifications de l’épidémiologie des VAP
– A un risque élevé de sélection de germes
potentiellement résistants, de traitement difficile
– et à un taux d’échec élevé de l’antibiothérapie
initiale, source potentielle de surmortalité
The Cumulative Risk of VAP
(Cook & the CCCTG, Ann Intern Med, 1998)
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The Daily Risk of VAP
(Cook & the CCCTG, Ann Intern Med, 1998)
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The Protective Effect of Early Antibiotics
(Cook & the CCCTG, Ann Intern Med, 1998)
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Prophylaxie des pneumopathies par la
‘DDS’
8
méta-analyses
 Plus de 5000 malades
 Mais différents traitements
 …et utilité toujours controversée
Prophylaxie des pneumopathies par la
‘DDS’
Pneumopathies
Ttmt
Ctr
Mortalité
Ttmt
Ctr
TOPIQUES
MA indiv.
188/937
(20%)
351/1123
(31.3%)*
191/937
(20.4%)
217/1123
(19.3%)
MA aggreg.
196/1099
(18%)
380/1278
(30%)*
309/1183
(26%)
327/1360
(24%)
TOP+SYST.
MA indiv.
204/1303
(15.7%)
476/1338
(35.6%)*
281/1302
(21.6%)
340/1338
(25.4%)*
MA aggreg
226/1437
(15.7%)
493/1446
(34.1%)*
428/1779
(24%)
508/1802
(28.2%)*
D’Amico et al, BMJ 1998
SDD: Effet sur l'incidence des Infections
Respiratoires basses
45
40
35
30
25
20
15
10
5
0
Topical
Med
Chir
45
40
35
30
25
20
15
10
5
0
Ctr
Trauma
All
Top+Sys
Med
Chir
Ctr
Trauma
All
SDD: Effets sur la Mortalité
40
40
Topical
35
Ctr
35
30
30
25
25
20
20
15
15
10
10
5
5
0
0
Med
Chir
Trauma
All
Med
Chir
Top+Sys
Ctr
Trauma
All
Cefuroxime prophylaxis in comatose patients






Open, RCT cefuroxime (2 doses, n=53) vs. controls (n=52)
Incidence of pneumonia : 23% vs 48% (p=0.006)
EOP 8/12 (66%) vs. 18/25 (72%)
Factors associated with pneumonia :
– Duration MV (RR 1.1 / day);
– cefuroxime (RR 0.17); other prior antibiotic (RR 0.3)
Presence of GPC and H.influenzae in initial endotracheal
aspirate associated with EOP (RR 28.9; 1.6-525)
Microorganisms:
– MSSA 30%; H.influenzae 23%; S.pneumoniae 11%;
Enterobacteriaceae 19%; Pseudomonas / Acinetobacter 15%
Sirvent & al, AJRCCM 1997
Prévention des VAP: Antibiothérapie
systémique précoce?
Cefuroxime
(n=50)
Apache II
Controles
(n=50)
14 ± 5
13 ± 5
GCS
7.5 ± 2.4
8.0 ± 1.8
Pneumonie
suspectée
confirmée
19 (38%)
12 (23%)
33 (66%)
25 (48%)
13 ± 8
16 ± 11
DS Réa
Sirvent & al, AJRCCM 1997
P
0.006
Stratégie de Prévention des Pneumopathies
Nosocomiales
 Facteurs
intrinsèques
 Instrumentation des voies aériennes
 Co-Interventions
 Antibiothérapie
Stratégies de Prévention des Pneumopathies
Nosocomiales (1)
 Facteurs
intrinsèques
– Pathologies sous-jacentes broncho-pulmonaires
– Troubles neurologiques, coma
– Chirurgie thoracique, abdominale
 Positionnement du malade, kinésithérapie (lits basculants?)
 Instrumentation
des voies aériennes
 VNI
 Intubation orotrachéale, réintubation
 Changement et manipulations des circuits (filtres ECH?)
 Précautions de contact (aspirations circuit fermé?)
 Drainage sécrétions sous-glottiques (?)
Stratégies de Prévention des Pneumopathies
Nosocomiales (2)
 Co-Interventions
– Sédation, curarisation
– Prophylaxie anti-ulcéreuse (?)
– Nutrition entérale (?)
 Antibiothérapie
 À évaluer
systémique ?