Conduite à tenir devant une suspicion dinfection liée aux cathéters en réanimation...
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Conduite à tenir devant une suspicion d’infection liée aux cathéters en réanimation Jean-François TIMSIT CHU Grenoble UJF/Inserm U 823 t Etienne – Juin 2009
Conduite à tenir devant une suspicion dinfection liée aux cathéters en réanimation Jean-François TIMSIT CHU Grenoble UJF/Inserm U 823 St Etienne – Juin
Conduite tenir devant une suspicion dinfection lie aux cathters
en ranimation Jean-Franois TIMSIT CHU Grenoble UJF/Inserm U 823 St
Etienne Juin 2009
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Faible niveau de preuve ILC : Le traitement depend de svrit du
sepsis svrit du sepsis maladies sous-jacente (immunodpression,
prothses). maladies sous-jacente (immunodpression, prothses).
Micro-organismes identifis ou suspects Micro-organismes identifis
ou suspects HC positives ou ngatives HC positives ou ngatives
Utilit et facilit de labord veineux central Utilit et facilit de
labord veineux central
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Deux constraintes : Eviter lablation inutile des CVCs (75%
cases) et le risque associ de complications mcaniques Sauver les
malades et viter que linfection se complique En cas de sepsis grave
le cathter DOIT tre enlev
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2 situations Sepsis svre de cause inconnu Ablation du CVC (ou
change sur guide?) Quels antibiotiques? Comment dpister les
complications et les traiter? Fivre sans signes de sepsis svre en
ranimation Hmoculture positive Est il possible de conserver le
cathter sans risques?
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Le cathter? 1.Ablation du cathter Est associe un plus grand
nombre de gurison et une amlioration du pronostic 2. Diagnostic
cathter en place 3. Echange sur guide (GWX)
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Biofilm formation Schneegurt, MA. Wichita St. University,
Microbiology 103.
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Why form a bioflim? Jefferson KK. FEMS. 2004;236:163-73.
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Susceptibility of biofilm organisms OrganismAntibiotic MIC or
MBC (mcg/mL) Effective [ ] vs. biofilm (mcg/mL) S. aureus (NCTC
8325-4) Vancomycin2 (MBC)20 P. aeruginosa (ATCC 27853) Imipenem1
(MIC)>1,024 E. coli (ATCC 25922) Ampicillin2 (MIC)512 P.
pseudomalleiCeftazidime8 (MBC)800 S. sanguisDoxycycline0.063
(MIC)3.15 Adapted from Donlan RM, et al. Clin Microbiol Rev.
2002;15:167-93. Minimal biofilm eradication
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1- Bacterias with slime production have an increased MICs and
MBCs to ABx 2- The Biofilm increases the resistance of bacteria to
ABt SCN culture CVC maintenance is always risky
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-Decrease of the duration of the candidemia New site 5.6 days
vs Other 2.6 days - Bias: APACHE II 14.5 vs 16.9 p=0.03 Other
catheter: 1.2 vs 1.8,p
Management of CVCs in patients with cancer and candidemia Raad
I et al Clin Infect Dis 2004; 38:1119 1993-1998: 404 episodes of
candidemia (50% ICU) with 1 CVCs for more than 1 days 3 categories
Primary candidemia : 241 (60%) Secondary candidemia: 52 (13%) CVC
related candidemia : 111 (27%) + tip cult (66) or quantitative BC
> 5:1 (45) %
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Outcome of candidemia: time of catheter removal after the first
positive culture Raad I et al Clin Infect Dis 2004; 38:1119
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Predictors of failure to respond to antifungal therapy Raad I
et al Clin Infect Dis 2004; 38:1119
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Is candidemia catheter-related? Raad I et al Clin Infect Dis
2004; 38:1119 111 catheter-related candidemia and 52 secondary
candidemia No corticosteroids within 1 month:OR 3.5 (1.3-9.4),
p=0.02 No chemotherapy within 1 month: OR 4.3 (1.5-13.3), p 15
cfu/ml Maki et al. N Engl J Med 1977; 296: 1305-1309 Culture
quantitative: Portion endo et extra-luminale prfrable
ultrasonication Sherertz et al J Clin Microbiol 1990 Vortexage dans
1 ml de RL strile Brun-Buisson - Arch Int Med 1987; 147:873
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Influence de la culture des KT sous antibiotiques actifs KT
intrapritonaux/souris Infects S. epi puis trait par TEICO ou RMP A
J1 culture neg ou micro-colonies Culture vs dtection du mRNA
(bactries viables)+PCR quanti J2 Vandecasteele et al Diagnostic
Microbiology and Infectious Diseases 48 (2004) 8995 Contrle 94%
(30/32) TEICO 72% (49/68) 81% (55/68) Sensibilit >1000 cfu/ml
>100 cfu/ml RMP 86% (62/72) 94% (68/72)
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The CVC ? 1.CVC removal 2.Diagnosis catheter in place Direct
examination Other methods based on culture results 3. Guidewire
exchange (GWX)
Diagnostic catheter in place A negative cutaneous swab culture
of skin entry 100% Negative predictive value Paired
(Peripheral/central) quantitative BC > 5/1 or Differential time
to positivity of BC > 120 mn Se/Sp > 90%
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Culture cutane: valeur prdictive 134 CVC de ranimation, 70%
S.clav. Dure d'insertion:10 + 6 jours couvillonnage de 25 cm 2 site
d'insertion 75 cultures peau positives / 26 CVC > 10 3 cfu/ml
concordance bactrienne avec la culture du KT dans 23/24 cas de
colonisation de CVC Se 92.3% Sp 52.7% VPP: 32% VPN 96.7% VPP moins
bonne pour les G+ (24% vs 47%) Mah I et al. Reanim Urg
1998;7:17
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Prlvements cutans orients 132 Kt, hmatologie, culture (Maki
+Sheretz) Cultures systmatiques tous les mois vs Culture en cas de
suspicion d'infection N 87 15 Se 18 75 Sp 83 100 VPP 13 100 VPN 88
92 Systmatiques Orients Raad Clin Infect Dis 1995; 20:593 (*)
couvillon de 24 cm 2, culture quantitative en milieu liquide
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Test diagnostic rapide 100 L de sang par le KTC Traitement par
l'acide dtique lyse et centrifugation puis pastilles de
cytocentrifugation puis coloration acridine orange et Gram 100
champs, 2 colorations Kite et al Lancet 1999; 354:1504 ILC+ 48 2
ILC- 5 57 Gram + AOLC test Positif Ngatif
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Endoluminal brush and Acridine Orange stain Diagnosis of
Catheter - Related Infections Tighe et al. J Parent Enter Nutr
1996; 20: 215-218 Group 1: Acridine orange stain Group 2: Acridine
orange stain and endoluminal brush 50 CVC 2 AOLC + 15 AOLC + 50 CVC
17 cult + 18 cult + Se: 18% Se: 83%
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Hmoculture quantitative comparative en ranimation 14/283
infects, 19 ont au moins une HC sur CVC + Seuil KT/P=2Se 98 %Sp 98%
Seuil KT/P=8Se 92.8 %Sp 98.8% Seuil KT/P=100Se 79%Sp 99% Que faire
des HC centrales positives isoles? Quilici - CID 1997; 25:1066
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Dlai de positivit des hmocultures (DTP) Dlai de positivit des
hmocultures (DTP) HC sur cathter HC sur cathter HC priph. Turbidit
du sang fonction de linoculum bactrien 0 4 8 heures DPT = 4 h.
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Dlai de positivit Validation in-vitro Blot F et al - J Clin
Microbiol. 1998;105-109 Validation in-vivo (ranimation
cancrologique) Seuil DTP= 120 mn Blot F - Lancet 2000; 354: 1071
MAIS Que faire de hmocultures dissocies? Explore essentiellement le
mode de contamination endoluminaleutilit en ranimation? Rijnders BJ
et al - Crit Care Med. 2001 Jul;29(7):1399-403 Cependant valeur
diagnostique aussi bonne pour les CVCs de moins ou de plus de 30
jours Raad et al Ann Intern Med 2004; 140:18-25
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14 mois, 93 suspicions d ILC CVC courte et longue dure,
dispositifs implantables Paires d hmocultures et ablation du KT
dans les 48 heures Sp: 91 (95% CI 59 -100%) Se: 94 (95% CI 71 -
100%) Blot F - Lancet ; 354: 1071-77 2 heures 120min
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Paired blood cultures Total CRI Absence of CRI Positive (H+/P+)
28 17 11 DTP >120 min 17 16 1 DTP
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Endoluminal colonization: in which lumen? Dobbins et al CCM
2003; 31: 1688 CVCs not suspected No CRBSI (n=50) CVCs suspected No
CRBSI (n=25) CVCs suspected CRBSI (n=25) N lumens colonized* 1 2 3
630630 430430 10 5 N CVCs Maki roll +281420 (*) endoluminal
brushes> 100 CFUs
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Watchful waiting vs immediate CVC removal in the ICU - Rijnders
BJ et al Intens Care Med 2004; 30: 1073-80 Exclusion: Neutropenia,
foreign body, transplantation BSI (positive BC) Erythema,
induration or purulence HD instability Previous DNR
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Watchful waiting vs immediate CVC removal in the ICU - Rijnders
BJ et al Intens Care Med 2004; 30: 1073-80 (2) New Abx after
inclusion: 13 of 32 patients in the WW 22 of 32 in the
SOC-(P=0.04).
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limitations Weak and subjective exclusion criterias Low power
Rate of non bacteremic sepsis not reported Decrease in the rate of
suspicion of CR-BSI during the study: First half 85/704 vs 2nd half
59 / 790 p=0.003 Rijnders BJ et al Intens Care Med 2004; 30:
1073-80
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The CVC ? 1. CVC removal 2. Diagnosis catheter in place 3.
Guidewire exchange (GWX) Associated with fewer mechanical
complications OR: 0.48 [[0.89-3.33] But a trend toward a higher
risk of infection of the 2nd CVCs OR: 1.72 [0.89-3.33] Cook DJ Crit
Care Med 1997;25:1417
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Changement sur guide 158 changements sur guide / 13 cultures de
guide positives (8.2%) Mme germes sur les 2 CVCs et le guide dans 6
/ 7 cas Colonisation du guide prdictif de la colonisation du CVC
pos (p=0.05) Palmer S ICHE 2005; 26:506
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Guidewire exchange (GWX) 1. When to start antimicrobials?
Before the guidewire exchange Before the guidewire exchange 2.
Attitude with the second CVC Keep it if culture neg. Keep it if
culture neg. Remove it if culture pos. Remove it if culture pos. It
might be possible to keep the 2nd CVC in case of CNS or
Enterobacteriaceae???? It might be possible to keep the 2nd CVC in
case of CNS or Enterobacteriaceae????
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Critres diagnostiques Infection bactriemique CVC + ou HC
diffrentielles + ou culture du site dinsertion + et HC au mme germe
Absence dautre site + expliquant les HC ILC non bact ri mique
C.V.C.+ Et Une r gression totale ou partielle dans les 48 h ou
Orifice purulent ou tunnelite. Ractualisation du consensus
Ranimation 2003;12: 258-265
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Catheter tip colonization: a surrogate? Meta-analysis 1990-
2002 randomized study 29 studies selected Quantitative or
semiquantitative cult and CR- BSI Correlation: R squared= 0.48,
p< 0.001 BSI=0.77 + 0.73(CTC) Rijnders et al Clin Infect Dis
2002; 9:1053
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Should we always prescribe systemic antimicrobials ? Always if
severe sepsis or septic shock Always if severe sepsis or septic
shock Positive blood cultures Positive blood cultures - Yes, always
- For CNS (2 positive BC) In case of negative BC ????
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Which micro-organisms are associated with severe complications?
?(n = 102) Shock Sepsis Thrmb. Sept. Other Total (%)* Shock Sepsis
Thrmb. Sept. Other Total (%)* CNS3 1 1 1 6/33 (18) S. aureus3 3 4
812/32 (38) Enterococci0 0 0 0 0/3 GNB2 0 0 0 2/10 (20)
P.aeruginosa1 0 1 0 2/4 (50) Candida spp.0 7 0 0 7/11 (64)
Polymicrob.2 1 1 0 4/9 (44) * Nb Complications/Nb of events Arnow
PM et al. 1993 Clin Infect Dis
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CVC > 15 cfu - S aureus Ruhe et al CMI 2006- 12; 933-935 101
CVC+ HC non faites ou neg 24 exclus 3 Inf invasive SA 11 Perdu de
vue 3 DCD4OR=9, p=0.02 Pas de Tt dans les 48 h OR=21, p=0.002
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CVC > 15 cfu - S aureus Ruhe et al CMI 2006 12; 933-935 77
CVC+ Appari 77 CVC- sur age, Charlson, provenance
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CVC > 15 cfu - S aureus Ekkelenkamp et al CID 2008; 46:114
184 CVC+ HC faites 85 HC + dans les 24 h 99 CVC+ Tt dans les 48h
N=50 2 HC+ dans les 30j 4% Pas de traitement N=49 12 HC+ dans les
30 j 25%
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CVC > 15 cfu - S aureus Ekkelenkamp et al CID 2008; 46:114
in the absence of randomized prospective trials, the best available
evidence supports rapid antibiotic treatment of all patients with
S. aureuspositive IV catheter tips.
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CVC > 15 cfu S. aureus Zafar et al JHI 2008; Dure de CVC:
Med 8 (1-327) Fivre:77% MRSA 73% SAB: 4/74 (5.4%)
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58 patients CVC > 10 3 cfu/ml Candida sp. neg blood cultures
Only one patient developed IC (detected as candidemia). 12/33
patients (36.4%) with a clinical improvement 8/25 (32.0%) with a
poor outcome received SAT RF of poor outcome: Ultimately fatal
underlying disease OR 12; 95% CI, 1.4105 P = 0.025 Severe sepsis,
septic shock or MOF OR 6.2; 95% CI, 1.038; P = 0.05 BUT NOT
Antifungal use:OR 0.82; 95% CI, 0.272.47; P = 0.73). Antifungals
for CVC tip > 10 3 Cfu/ml (retrospective) Perez-Parra Intensive
Care Med (2009) 35:707712
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Antimicrobials (BC neg) SituationAntimicrobials Candida spp, S.
aureus or P. aeruginosa Candida spp, S. aureus or P. aeruginosa
Sepsis after CVC removalYes No fever after CVC removalYes ? (SA)
Other micro-organisms Fever after CVC removalNo* Fever after CVC
removalNo* If GWX or CVC in placeYes??
__________________________________________________ * Except
immunosuppression
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Quelles molcules doit t on utiliser? REA-RAISIN 2006-2007 57
centres (8425 pts) Colonisation CNS 43 % S. aureus 15 % Entrocoques
5 % BGN dont pyocyanique 37 % 15 % Candida 4.5 % Infection 33 % 22
% 7 % 40 % 17 % 6 %
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Grandes variations selon les centres
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Lpidmiologie varie en fonction des annes et des pidmies from
U.H.L.I.N Bichat: I Lolom, JC Lucet
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Groupes (N /N events) S. aureus SCN Enterococcus P. aeruginosa
A. baumannii E. coli Autres Gram neg. Champignons Culture >10 3
cfu/ml Tunneliss (15/14) 1 4 0 3 2 1 Controles (21/19) 1 4 1 4 1 2
7 1 Infection sytmique de KT Tunneliss (6/5) 0 2 1 Controles
(17/15) 1 2 1 4 0 2 6 1 Microorganismes voie fmorale Timsit et al
Ann intern Med 1999 9 21 2 4 17 2
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Choice of the molecules Situations active on CNS If severe,
consider immediately GNB and yeast Molecules Glycopeptide +
gentamicin If GNB suspected: activity against P. aeruginosa
Candida: fluconazole (800 mg laoding dose) or echinocandins
(unstable patients) Rex et al N Engl J Med 1994 ;331:1325, Reboli
et al NEJM 2008 Antimicrobials should be adapted to blood and
catheter cultures AmpB L? LNZ? Daptomycin?
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Biofilm production and antifungal effects In the biofilm (C.
albicans and C. glabrata): AMPHO B > Voriconazole >
fluconazole Regrowth was noted in the biofilm Lewis et al
Antimicrob Agent Chemother 2002; 3499 Killing of the biofilm cells
better with echinocandins (caspofungin) (activity against fungal
cell wall +++) Kuhn DM - Antimicrob Agent Chemother 2002; 1773
Ramage R - Antimicrob Agent Chemother 2002; 3634 Bachmann SP-
Antimicrob Agent Chemother 2002;3591
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Nouvelles molecules Cet AM.
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What should be done in case of failure ? (sepsis and/or + BC
> 3 days) Pharmacologic failure MRSA/glycopeptides
Thrombophlebitis Thrombophlebitis New CVC colonization New CVC
colonization Other septic foci (endocarditis+++) Other septic foci
(endocarditis+++)
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Vancomycin Pharmacocinetic variable and unpredictable:
Dosage+++ Low level associated with failure Maintain trough >
15-20 g/ml especially if MIC > 1 g/ml Consider association:
Gentamicin if possible, rifampin, linezolid?,
dalfopristin-quinupristin? SUBSEQUENT DE-ESCALATION IF Methicillin
sensitive+++
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High MICs and failure MRSA BSI Vancomycin > 24h Survival
> 24h Loidise et al - AAC, Sept. 2008, p. 33153320
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Daptomycin vs vancomycin gentamicin bacteremia MRSA Persisting
or relapsing bact Dapto 27%- Van-Gen 21% Death dapto 12/45 (27%)
Death Vanco 8/43 (19%) Rehm SJ et al JAC 2008
doi:10.1093/jac/dkn372 a,b:Success rate
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Septic thrombophlebitis Clinically silent Ultrasound Doppler.
Ligation of the vein: very invasive, rarely indicated Optimizing
the antimicrobial : Antibiotic dosing, 2 antimicrobials Longer
duration: 4-6 weeks Heparin and fibrinolytic ?
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Venous thrombosis in patients with short and long term CVC
related S aureus bacteremia Crowley et al - Crit Care Med 2008;
36:385 N=48, Thrombosis:71% Cure 23/34 (68%)Cure 12/14 (86%)
Page 68
Trans-oesophagal echography and S.aureus n 7 26 * * P <
0,0005 Adapted from Fowler et al. JACC 1997
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Malanovski GJ - Arch Intern Med 1995;155:1161 Duration of
treatment and complications: P=0.01 S. aureus: Relapse increases if
treatment is less than 10 days
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S. aureus CRB : Short treatment Meta-analysis 11 studies/ 132
Pts Late complications after treatment < 14 days 6.1% [95% CI,
2.0% - 10.2%] Rare but severe: 3 Endocarditis (1 surgery) 2
epidural abscesses (1 surgery) 2 bacteremias (1 death) Jernigan et
al - Ann Intern Med 1993;119:304
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Enlever KT ATB 5 7 j KT en place ATB 10 14 j +/- verrou Enlever
KT ATB 14 j Enlever KT ATB 10 14 j Enlever KT ATB 14 j aprs dernire
HC + Bactrimies sur KT IDSA, CID, 2001 Infection complique
Infection non complique Oter le KT ATB prolonge 4 8 semaines
Thrombophlbite Endocardite Ostomylite Staph coag
negS.aureusBGNCandida Voir pour ETO
Page 72
Nothing!! Nothing!! Probably not justified in immunocompetent
afebrile pt after CVC removal ? Probably not justified in
immunocompetent afebrile pt after CVC removal ? S. aureus (and P.
aeruginosa) or immunosupression S. aureus (and P. aeruginosa) or
immunosupression ?? (5-7d?) ?? (5-7d?) Duration of treatment
proposals (Negative BC)
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Antibiotic lock in ICU? Antimicrobial concentration high (X 50
to 100) Volume 2 ml (+ hparine if vanco, cipro, teico) Anticrobials
stable: (even with heparine) vanco, cefazolin, ticar-clavu,cipro
(Anthony et al, AAC 1999;2074) New locks:Minocyclin-EDTA, Ethanol,
Taurolidine CVC use is impossible during the lock Injection 2 fold
a day, for 2 to 3 weeks Associated IV antimicrobials
Contra-indications: fungal infections, neutropenia,
thrombophlebitis, tunnelitis, septic shock
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Verrou (VLA) ou AB IV AB IV seulsVLA +/- AB IV 14 essais (1982
1995) Succs: 342/514 (66,5%) CVC tunnliss 7 essais (1990 1995)
Succs: 138/167 (82,6%) Chambres implantables 5 essais (1988 2001)
Succs : 90/120 (75%) Problmes de dfinition des infections Sites
dinfection inconstamment cits Paramtres dvaluation de lefficacit
diffrents
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AAC 2007; 78-83 (*)I.R. is the inventor of catheter lock
technology that involves alcohol. This patent is the property of
The University of Texas M. D. Anderson Cancer Center.
Page 77
Arch Pediatr Adolesc Med. 2006;160:1049-1053 Treatment success
was defined as resolution of fever within 24 hours, no recurrence
of positive blood cultures with the same organism, and retention of
the IVD. Treatment failure was defined as recurrence within 30 days
with the same pathogen or removal of the IVD because of a
persistent infection. 70% Ethanol lock 45/51 success
Page 78
Comit d'organisation : Responsables pour la commission des
rfrentiels: B Guidet, R Robert, M Wolff, S Leteurtre Charg de
projet : adulte : JF Timsit, pdiatrie : Ph Durant Experts : adulte
: G Nitenberg, pdiatrie : Dageville Membres de l'ancien jury : G
Bleichner, Y Letulzo, M Pinsard. Experts extrieurs : JC Lucet, B
Souweine, L Soufir, P Longuet, J Merrer, A Lepape, F Blot, C
Martin, G Nitenberg, O Mimoz, Ph Eggiman, G Colas, C Brun-Buisson
Reanimation 2003
Page 79
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Enlever KT ATB 5 7 j KT en place ATB 10 14 j +/- verrou Enlever
KT ATB 14 j Enlever KT ATB 10 14 j Enlever KT ATB 14 j aprs dernire
HC + Bactrimies sur KT IDSA, CID, 2001 Infection complique
Infection non complique Oter le KT ATB prolonge 4 8 semaines
Thrombophlbite Endocardite Ostomylite Staph coag
negS.aureusBGNCandida Voir pour ETO