Conduite à tenir devant une suspicion d’infection liée aux cathéters en réanimation

Conduite tenir devant une suspicion dinfection lie aux cathters en ranimation

Jean-Franois TIMSITCHU GrenobleUJF/Inserm U 823St Etienne Juin 2009

ILC : Le traitement depend deFaible niveau de preuvesvrit du sepsis maladies sous-jacente (immunodpression, prothses). Micro-organismes identifis ou suspects HC positives ou ngatives Utilit et facilit de labord veineux central

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

2 situationsSepsis svre de cause inconnuAblation du CVC(ou change sur guide?)

Quels antibiotiques?Comment dpister les complications et les traiter?Fivre sans signes de sepsis svre en ranimationHmoculture positive

Est il possible de conserver le cathter sans risques?

Le cathter?Ablation du cathterEst associe un plus grand nombre de gurison et une amlioration du pronostic2. Diagnostic cathter en place3. Echange sur guide (GWX)

Biofilm formationSchneegurt, MA. Wichita St. University, Microbiology 103.

Why form a bioflim?Jefferson KK. FEMS. 2004;236:163-73.

Susceptibility of biofilm organismsAdapted from Donlan RM, et al. Clin Microbiol Rev. 2002;15:167-93. Minimal biofilm eradication

1- Bacterias with slime production have an increased MICs and MBCs to ABx2- The Biofilm increases the resistance of bacteria to ABtSCN cultureCVC maintenance is always risky

-Decrease of the duration of the candidemiaNew site 5.6 days vs Other 2.6 days

- Bias: APACHE II 14.5 vs 16.9 p=0.03Other catheter: 1.2 vs 1.8,p

Management of CVCs in patients with cancer and candidemia Raad I et al Clin Infect Dis 2004; 38:11191993-1998: 404 episodes of candidemia (50% ICU) with 1 CVCs for more than 1 days3 categoriesPrimary candidemia : 241 (60%)Secondary candidemia: 52 (13%)CVC related candidemia : 111 (27%)+ tip cult (66) or quantitative BC > 5:1 (45)%

Outcome of candidemia: time of catheter removal after the first positive culture Raad I et al Clin Infect Dis 2004; 38:1119

Predictors of failure to respond to antifungal therapy Raad I et al Clin Infect Dis 2004; 38:1119

Is candidemia catheter-related? Raad I et al Clin Infect Dis 2004; 38:1119111 catheter-related candidemia and 52 secondary candidemia

No corticosteroids within 1 month:OR 3.5 (1.3-9.4), p=0.02No chemotherapy within 1 month: OR 4.3 (1.5-13.3), p

Proposed algorythm for candidemia Raad I et al Clin Infect Dis 2004; 38:1119

Absence of CVC removal is always riskyCandida sp: 427 CRBDeath 41% vs 21 %Nguyen et al - Arch Intern Med 1995;155:2429S. aureus: 50 CRB (retrospective)Persistent BC:11 vs 56% (p=0.01), Deaths: 5 vs 20%Malanovski GJ - Arch Intern Med 1995;155:1161X. maltophilia: % cured: 49/49 vs 32/62 (p

In case of tunnelitis Antimicrobials alone is not sufficient

Microorganisms Cured Failures (n=5) (n=15)

S. aureus11

P. aeruginosa 0 7

polymicrobial 1 5*

Negative culture 3 2

* 4 with P. aeruginosa et 1 with P. maltophiliaBenezra et al, Am. J. Med., 1988, 85, 495

Culture aprs ablation des cathtersCulture qualitative (trop peu spcifique abandonner)

Culture semi-quantitative+ si > 15 cfu/mlMaki et al. N Engl J Med 1977; 296: 1305-1309

Culture quantitative: Portion endo et extra-luminale prfrableultrasonicationSherertz et al J Clin Microbiol 1990 Vortexage dans 1 ml de RL strile Brun-Buisson - Arch Int Med 1987; 147:873

Influence de la culture des KT sous antibiotiques actifsKT intrapritonaux/sourisInfects S. epi puis trait par TEICO ou RMP A J1 culture neg ou micro-coloniesCulture vs dtection du mRNA (bactries viables)+PCR quanti J2Vandecasteele et al Diagnostic Microbiology and Infectious Diseases 48 (2004) 8995Contrle

94% (30/32) 94% (30/32)TEICO

72% (49/68)81% (55/68)Sensibilit

>1000 cfu/ml>100 cfu/mlRMP

86% (62/72)94% (68/72)

The CVC ?CVC removalDiagnosis catheter in placeDirect examinationOther methods based on culture results3. Guidewire exchange (GWX)

Modes de colonisationsEndoluminaleExtraluminale

Endo ou extra-luminale?Cercenado 1990

Fan 1988

Cicco 1989

Salzman 1993

Linares 1985

Segura 1993

Weightman 1988

Nb KT/dure

139/8.6

156/ 15

109/18.2

113/23.9

22/20

400/23

42/ 114Nb inf sys

53

11

6

28

20

24

11Hub

12

1

3

21

14

9

8Peau

30

4

3

7

2

5Mixte

8

2

2

Les Signes locaux ont peu de valeur diagnostique (1263 CVCs)

P> 0.5 pour toutes les comparaisons(*) douleur, coulement et purulence ntaient prsent dans aucune des ILC (27/35 SCN mme pulsotype)

Safdar N, Maki DG Crit Care Med 2002; 30:2632-2635

N (%)ILC * n=35Colonisation n=333Strile n=894

Douleur (0-1)25 (2%)0.00.2 0.40.2 0.4

Erythme (0-2)25 (2)0.00.1 0.30.1 0.2

Ecoulement (0-1)126 (10)0.2 0.40.1 0.40.1 0.4

Purulence (0-1)10 (0.8)00 0.10

Total (0 5)126 (10)0.2 0.40.1 0.10.1 0.1

3

1098 patients, Mean apacheII=2

Inflammation at the insertion site is not predictive of catheter-related bloodstream infection with short-term, noncuffed central venous catheters* Nasia Safdar, MD; Dennis G. Maki, MD Background: Noncuffed, percutaneously inserted central venous catheters (CVCs) are widely used and cause at least 250,000 bloodstream infections (BSIs) in U.S. hospitals each year. We report a prospective study to determine whether inflammation at the insertion site is predictive of CVC-related BSI.Methods: Percutaneously inserted, noncuffed CVCs inserted into the subclavian, internal jugular, or femoral vein in two randomized trials during 1998-2000 were prospectively studied; most patients were in an intensive care unit. The condition of the insertion site was evaluated daily by research nurses, quantifying pain (0, 1), erythema (0-2), swelling (0, 1), and purulence (0, 1); the lowest possible overall inflammation score was 0 and the highest was 5. CVC-related BSI was confirmed in each case by demonstrating concordance between isolates from the catheter segment and from blood cultures by restriction-fragment DNA subtyping.Results: Among 1,263 CVCs prospectively studied, 333 (26.3%) were colonized at removal; of these, 35 catheters (2.7%) caused BSIs (5.9 per 1000 CVC days). BSIs were caused by coagulase-negative staphylococci (n = 27), enterococci (n = 4), enteric Gram-negative bacilli (n = 3), or Candida (n = 1). Most insertion sites showed little or no inflammation at the time of removal. There were no significant differences among mean scores for each inflammatory variable examined or overall score among colonized CVCs (0.1 0.1), catheters causing CVC-related BSI (0.2 0.4), and noncolonized CVCs (0.1 0.1). The sensitivity of local inflammation for diagnosis of CVC-related BSI was dismal (0-3%).Conclusion: Local inflammation is uncommon with infected CVCs, probably because most catheter-associated infections are currently caused by coagulase-negative staphylococci, a pathogen that incites little local or systemic inflammation. Whereas overt inflammation of the insertion site should raise suspicion of CVC-related BSI caused by Staphylococcus aureus or Gram-negative bacilli, especially if the patient has fever or other signs of sepsis, in general, site appearance cannot be relied on to identify catheter colonization or CVC-related BSI.3 other studies:. In a prospective study of 169 CVCs used mainly for parenteral nutrition, Armstrong et al. ( 10) found that ">4 mm of erythema at the insertion site was associated with a three-fold increased risk of catheter colonization (">15 colony-forming units; relative risk, 2.97; p = .06); swelling or tenderness was not predictive of colonization. Unfortunately, the report gives no information on catheter-related BSIs, particularly whether erythema was predictive of BSI.A prospective study of 1,353 CVCs in a university hospital showed that out of 11 cases of CVC-related BSI, 73% of patients had no signs of local inflammation, and the sensitivity and positive predictive value of local inflammation for identification of CVC-related BSI were 27% and 1.5%, respectively. However, purulence at insertion sites, although rare, was found to be highly predictive of CVC-related BSI in a univariate analysis (relative risk, 27.1; p

Diagnostic catheter in placeA negative cutaneous swab culture of skin entry 100% Negative predictive value

Paired (Peripheral/central) quantitative BC > 5/1orDifferential time to positivity of BC > 120 mnSe/Sp > 90%

Culture cutane: valeur prdictive134 CVC de ranimation, 70% S.clav.Dure d'insertion:10 + 6 jourscouvillonnage de 25 cm2 site d'insertion75 cultures peau positives / 26 CVC > 103cfu/mlconcordance bactrienne avec la culture du KT dans 23/24 cas de colonisation de CVCSe 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

Prlvements cutans orients132 Kt, hmatologie, culture (Maki +Sheretz)Cultures systmatiques tous les mois vs Culture en cas de suspicion d'infectionN8715Se 1875Sp83100VPP13100VPN8892SystmatiquesOrientsRaad Clin Infect Dis 1995; 20:593(*) couvillon de 24 cm 2, culture quantitative en milieu liquide

Test diagnostic rapide100 L de sang par le KTCTraitement par l'acide dtique lyse et centrifugation puispastilles de cytocentrifugation puis coloration acridine orange et Gram100 champs, 2 colorations

Kite et al Lancet 1999; 354:1504ILC+

48

2ILC-

5

57Gram + AOLC test

Positif

Ngatif

Endoluminal brush and Acridine Orange stainDiagnosis of Catheter - Related InfectionsTighe et al. J Parent Enter Nutr 1996; 20: 215-218Group 1: Acridine orange stain Group 2: Acridine orange stain and endoluminal brush 50 CVC2 AOLC +15 AOLC + 50 CVC17 cult +18 cult +Se: 18%Se: 83%

Hmoculture quantitative comparative en ranimation14/283 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

Dlai de positivit des hmocultures (DTP) HC sur cathter HC priph.Turbidit du sang fonction de linoculum bactrien 0 4 8 heures 0 4 8 heures DPT = 4 h.

Dlai de positivit des hmocultures (DTP)

HC sur cathter

HC priph.

Turbidit du sang fonction de linoculum bactrien

0 4 8 heures

0 4 8 heures

DPT = 4 h. >120min

Dlai de positivit

Validation in-vitro Blot F et al - J Clin Microbiol. 1998;105-109Validation in-vivo (ranimation cancrologique)Seuil DTP= 120 mn Blot F - Lancet 2000; 354: 1071

MAISQue 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 joursRaad et al Ann Intern Med 2004; 140:18-25

Dlai de positivit des HC: In vitroCorrelation Innoculum : vitesse de positivit

Blot F et al - J Clin Microbiol. 1998;105-109

14 mois, 93 suspicions dILC

CVC courte et longue dure, dispositifs implantables

Paires dhmocultures 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

8

Dlai de positivitValidation in-vitro Blot F et al - J Clin Microbiol. 1998;105-109Validation in-vivo (ranimation cancrologique)Seuil DTP= 120 mn Blot F - Lancet 2000; 354: 1071

MAISQue 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 joursRaad et al Ann Intern Med 2004; 140:18-25

14 mois, 93 suspicions dILC

CVC courte et longue dure, dispositifs implantables

Paires dhmocultures et ablation du KT dans les 48 heures

Sp: 91 (95% CI 59 -100%)Se: 94 (95% CI 71 - 100%)Blot F - Lancet ; 354: 1071-772 heures120min

Paired blood cultures Total CRI Absence of CRI

Positive (H+/P+) 28 17 11 DTP >120 min 17 16 1 DTP

Paires dHC (n=6138)

P-/C-N=5128 (83.5%)

P-/C+N=603 (9.8%)

P+/C-N=191 (3.1%)

P+/C+N=216 (3.5%)

P+/C+N=25 (0.5%)Germes diffrents

P+/C+N=192 (3%)Mme germe

Raad et al Ann Intern Med 2004; 140:18-25

Raad et al Ann Intern Med 2004; 140:18-25

Effets de lantibiothrapie pralable et de la dure dinsertion du cathter sur la valeur diagnostique du DTP

Composite=culture quanti > 5/1 ou KT> 15 cfu et hc periph ou les 2Partial: hc quanti comparativeKt tip culture = meme germe sur le kt et les HC periph

Il ya une grosse difference daccuracy de la technique en fonction que lon utilise lune ou lautre des dfinitions+++

Endoluminal colonization: in which lumen? Dobbins et al CCM 2003; 31: 1688(*) endoluminal brushes> 100 CFUs

CVCs not suspectedNo CRBSI (n=50)CVCs suspectedNo CRBSI(n=25)CVCs suspectedCRBSI(n=25)N lumens colonized*12363043010105N CVCs Maki roll +281420

Watchful waiting vs immediate CVC removal in the ICU - Rijnders BJ et al Intens Care Med 2004; 30: 1073-80Exclusion:Neutropenia, foreign body, transplantationBSI (positive BC)Erythema, induration or purulenceHD instabilityPrevious DNR

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).

limitationsWeak and subjective exclusion criteriasLow powerRate of non bacteremic sepsis not reportedDecrease in the rate of suspicion of CR-BSI during the study:First half 85/704 vs 2nd half 59 / 790 p=0.003Rijnders BJ et al Intens Care Med 2004; 30: 1073-80

The CVC ?1. CVC removal2. Diagnosis catheter in place3. 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

Changement sur guide158 changements sur guide / 13 cultures de guide positives (8.2%)Mme germes sur les 2 CVCs et le guide dans 6 / 7 casColonisation du guide prdictif de la colonisation du CVC pos (p=0.05)Palmer S ICHE 2005; 26:506

Guidewire exchange (GWX)1. When to start antimicrobials? Before the guidewire exchange2. Attitude with the second CVC Keep it if culture neg. Remove it if culture pos. It might be possible to keep the 2nd CVC in case of CNS or Enterobacteriaceae????

Critres diagnostiquesInfection bactriemiqueCVC + ou HC diffrentielles + ou culture du site dinsertion +et HC au mme germeAbsence dautre site + expliquant les HCILC non bactrimiqueC.V.C.+EtUne rgression totale ou partielle dans les 48 h ouOrifice purulent ou tunnelite.Ractualisation du consensus Ranimation 2003;12: 258-265

Catheter tip colonization: a surrogate?Meta-analysis1990- 2002 randomized study 29 studies selectedQuantitative or semiquantitative cult and CR-BSI

Correlation: R squared= 0.48, p< 0.001BSI=0.77 + 0.73(CTC)Rijnders et al Clin Infect Dis 2002; 9:1053

Should we always prescribe systemic antimicrobials ? Always if severe sepsis or septic shock Positive blood cultures- Yes, always For CNS (2 positive BC) In case of negative BC ????

Which micro-organisms are associated with severe complications? ?(n = 102)

Shock Sepsis Thrmb. Sept. Other Total (%)*

CNS3 1 1 1 6/33 (18)S. aureus3 3 4 812/32 (38)Enterococci0 0 0 0 0/3GNB2 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 eventsArnow PM et al. 1993 Clin Infect Dis

CVC > 15 cfu - S aureus Ruhe et al CMI 2006- 12; 933-935101 CVC+HC non faites ou neg24 exclus3 Inf invasive SA11 Perdu de vue3 DCD4OR=9, p=0.02Pas de Tt dans les 48 h OR=21, p=0.002

CVC > 15 cfu - S aureus Ruhe et al CMI 2006 12; 933-93577 CVC+ Appari 77 CVC-

sur age, Charlson, provenance

CVC > 15 cfu - S aureus Ekkelenkamp et al CID 2008; 46:114184 CVC+HC faites85 HC + dans les 24 h99 CVC+Tt dans les 48hN=502 HC+ dans les 30j4%Pas de traitementN=4912 HC+ dans les 30 j25%

CVC > 15 cfu - S aureus Ekkelenkamp et al CID 2008; 46:114in the absence of randomized prospective trials, the best available evidence supports rapid antibiotic treatment of all patients with S. aureuspositive IV catheter tips.

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%)

58 patients CVC > 103 cfu/ml Candida sp. neg blood culturesOnly one patient developed IC (detected as candidemia).

12/33 patients (36.4%) with a clinical improvement8/25 (32.0%) with a poor outcome received SAT

RF of poor outcome: Ultimately fatal underlying disease OR 12; 95% CI, 1.4105 P = 0.025Severe sepsis, septic shock or MOF OR 6.2; 95% CI, 1.038; P = 0.05BUT NOT Antifungal use:OR 0.82; 95% CI, 0.272.47; P = 0.73).Antifungals for CVC tip > 103 Cfu/ml (retrospective)Perez-Parra Intensive Care Med (2009) 35:707712

Antimicrobials (BC neg)SituationAntimicrobials Candida spp, S. aureus or P. aeruginosaSepsis after CVC removalYes No fever after CVC removalYes ? (SA)Other micro-organisms Fever after CVC removalNo*If GWX or CVC in placeYes??__________________________________________________* Except immunosuppression

Quelles molcules doit t on utiliser?

REA-RAISIN 2006-200757 centres (8425 pts)ColonisationCNS43 %S. aureus15 %Entrocoques5 %BGNdont pyocyanique37 %15 %Candida4.5 %

Infection33 %22 %7 %40 %17 %6 %

Grandes variations selon les centres

Lpidmiologie varie en fonction des annes et des pidmiesfrom U.H.L.I.N Bichat: I Lolom, JC Lucet

Graph3

40830

1337134

14513122

15417103

32115111

164161

200061

255641

2248101

SCN

S. aureus

P. aeruginosa

Entrobactries

Levures

Colonisation de CVC (Bichat-Claude Bernard) 1995-2003

Feuil1

Surveillance des cathters (CVC + SG) - RI de 1995 2003 (patients hospitaliss de plus de 48h)

199519961997199819992000200120022003199519961997199819992000200120022003

CVC colonissn = 13n = 37n = 39n = 42n = 52n= 26n= 25n = 28n = 34Levures042311111

Rpartion des germesCitrobacter freundii001101211

Enterobacter cloacae021242213

Levures042311111E. coli000320204

Citrobacter freundii001101211Morganella spp000000012

Enterobacter cloacae021242213P. aeruginosa87131751068

E. coli000320204S. aureus0354114054

Morganella spp000000012SCN41314153216202522

P. aeruginosa87131751068Autres cocci gram +000000001

S. aureus0354114054Autres bacilles gram +000012101

SCN41314153216202522Autres pseudomonas000001010

Autres cocci gram +000000001Streptocoques groupe D130160411

Autres bacilles gram +000012101Autres Streptocoques000100010

Autres pseudomonas000001010klebsielle011130010

Streptocoques groupe D130160411Autres Bacilles gram -072203000

Autres Streptocoques000100010Proteus337120000

klebsielle011130010

Autres Bacilles gram -072203000

Proteus337120000

Total164346516731324448

199519961997199819992000200120022003

Levures042311111

Citrobacter freundii001101211

Incidence /1000j. De procdures (CVC + SG) - RI de 1995 2003 (patients hospitaliss de plus de 48h)Enterobacter cloacae021242213

E. coli000320204

199519961997199819992000200120022003Morganella spp000000012

CVC colonissn = 13n = 37n = 39n = 42n = 52n= 26n= 25n = 28n = 34P. aeruginosa87131751068

Incidence/1000 J.16.421.126.323.835.513.614.617.915.3S. aureus0354114054

SCN41314153216202522

Autres cocci gram +000000001

Autres bacilles gram +000012101

Bactrimie porte d'entre = CVCAutres pseudomonas000001010

Streptocoques groupe D130160411

BACTERIEMIE 1995Autres Streptocoques000100010

Nom-PrnomAdmis leDate Sept.GermesOrigineklebsielle011130010

Bellaiche Serge6/9/95AcinetobacterKTAAutres Bacilles gram -072203000

Bertelli Marie Line7/23/95P. aeruginosaCVCProteus337120000

Denon Simeone9/30/95P. aeruginosaCVCautre

P. mirabilisentrobactries31312101166410

Rieu Emilienne10/29/95ProteusCVC

1995 (16)1996 (43)1997 (46)1998 (51)1999 (52)2000 (31)2001 (32)2002 (44)2003 (48)

BACTERIEMIE 1996SCN41314153216202522

Nom-PrnomAdmis leDate Sept.GermesOrigineS. aureus0354114054

Cheneault Andr8/4/96AcinetobacterCVC ou KTAP. aeruginosa87131751068

Labache Etiennette11/28/96S. aureusCVCEntrobactries31312101166410

Ledroit Philippe4/12/96LevuresCVCLevures042311111

Total164346516731324448

BACTERIEMIE 1997

Nom-PrnomAdmis leDate Sept.GermesOrigine

Brenneur Arsene10/2/97S. aureusCVC1995 (16)1996 (43)1997 (46)1998 (51)1999 (52)2000 (31)2001 (32)2002 (44)2003 (48)

Chich Daniel7/3/97S. aureusType de Kt?SCN25%30%30%29%48%52%63%57%46%

Cognard Jean7/16/97P. aeruginosaCVC ou KTAS. aureus0%7%11%8%16%13%0%11%8%

Debrix Monique1/23/97S. aureusKTAP. aeruginosa50%16%28%33%7%3%0%14%17%

Demarez Marcelle2/11/97P. aeruginosaType de Kt?Entrobactries19%30%26%20%16%19%19%9%21%

Keita Moussa3/7/97P. aeruginosaCVCLevures0%9%4%6%1%3%3%2%2%

Maatseki Mohammed1/17/97P. aeruginosaCVCAutres6%7%0%4%10%10%16%7%6%

Semra Ahmed6/19/97Autres BGNKTA

Sissako Macire8/4/97P. aeruginosaCVC ou KTA

Truffy Joelle4/14/97S. aureusType de Kt?

BACTERIEMIE 1998


Le Bars Eric6/10/98LevuresType de Kt ?

BACTERIEMIE 1999


Cohen Marguerite2/12/99S. aureusCVC

Postel Michel7/20/99P. mirabilisCVC

Soussans Meyer10/5/99P. aeruginosaKTA

Denkiewicz Jan2/7/99K. pneumoniaeCVC

BACTERIEMIE 2000


Ba Eric5/10/00K. pneumoniaetype de KT ?

Delaplanche Micheline2/2/00P. mirabilistype de KT ?

P. aeruginosa

Vicent Antoine11/6/00Citrobactertype de KT ?

Strepto groupe D

Ditukayeno Matshozi12/2/00LevuresDsilet

Duchene Roger10/20/00LevuresKTA

BACTERIEMIE 2001


Trouillet Henri1/5/01E. cloaceaetype de KT ?

Rodriguez Franoise6/3/016/25/01SCNKTA

Zemzem Hedy10/31/0111/8/01E. cloaceaeCVC

BACTERIEMIE 2002


Poirier Michel2/6/022/16/02SCNCVC

Bekierman Henri2/7/022/14/02SCNCVC

Ragaru Andr4/16/024/23/02S. aureusCVC ou KTA

S. marcescens

Covex Angle5/17/025/29/02S. aureusCVC

BACTERIEMIE 2003


Paiva Maria3/6/023/23/02S. aureusCVC ou KTAPatiente sortie en 2003

Lemaire Robert1/8/031/17/03P. aeruginosaKTA

Ndour Daoud3/11/033/19/03MorganelleCVC

Bruneau Lucien8/29/039/14/03LevuresCVC

Bredas jacqueline9/13/039/22/03P. aeruginosaCVC ou dsilet

Feuil1

Levures

Citrobacter freundii

Enterobacter cloacae

E. coli

Morganella spp

P. aeruginosa

S. aureus

SCN

Autres cocci gram +

Autres bacilles gram +

Autres pseudomonas

Streptocoques groupe D

Autres Streptocoques

klebsielle

Autres Bacilles gram -

Proteus

Colonisation de CVC 1995-2003 (Bichat-Claude Bernard)

Feuil2

SCN

S. aureus

P. aeruginosa

Entrobactries

Levures

Colonisation des CVC (Bichat-Claude Bernard) 1995-2003

Feuil3

SCN

S. aureus

P. aeruginosa

Entrobactries

Levures

Autres

Colonisation de CVC (Bichat-Claude-Bernard) 1995-2003

SCN

S. aureus

P. aeruginosa

Entrobactries

Levures

Colonisation de CVC (Bichat-Claude Bernard) 1995-2003

Groupes(N /N events)

S. aureusSCNEnterococcus

P. aeruginosaA. baumanniiE. coliAutres Gram neg.

ChampignonsCulture >103 cfu/mlTunneliss(15/14)

140

3222

1Controles(21/19)

141

4127

1Infection sytmique de KTTunneliss(6/5)

000

2111

1Controles(17/15)

121

4026

1 Microorganismes voie fmoraleTimsit et al Ann intern Med 1999 92124172

Choice of the moleculesSituationsactive on CNSIf severe, consider immediately GNB and yeast MoleculesGlycopeptide + gentamicinIf GNB suspected: activity against P. aeruginosaCandida: 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?

Biofilm production and antifungal effectsIn the biofilm (C. albicans and C. glabrata):AMPHO B > Voriconazole > fluconazoleRegrowth was noted in the biofilmLewis et al Antimicrob Agent Chemother 2002; 3499Killing of the biofilm cells better with echinocandins (caspofungin) (activity against fungal cell wall +++)Kuhn DM - Antimicrob Agent Chemother 2002; 1773Ramage R - Antimicrob Agent Chemother 2002; 3634Bachmann SP- Antimicrob Agent Chemother 2002;3591

Nouvelles moleculesCet AM.

What should be done in case of failure ?(sepsis and/or + BC > 3 days) Pharmacologic failure MRSA/glycopeptides Thrombophlebitis New CVC colonization Other septic foci (endocarditis+++)

VancomycinPharmacocinetic variable and unpredictable: Dosage+++Low level associated with failureMaintain trough > 15-20 g/ml especially if MIC > 1 g/mlConsider association: Gentamicin if possible, rifampin, linezolid?, dalfopristin-quinupristin?

SUBSEQUENT DE-ESCALATION IF Methicillin sensitive+++

High MICs and failureMRSA BSIVancomycin > 24hSurvival > 24h

Loidise et al - AAC, Sept. 2008, p. 33153320

Daptomycin vs vancomycin gentamicin bacteremia MRSAPersisting or relapsing bactDapto 27%- Van-Gen 21%

Death dapto 12/45 (27%)Death Vanco 8/43 (19%) Rehm SJ et al JAC 2008 doi:10.1093/jac/dkn372a,b:Success rate

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 ?

Venous thrombosis in patients with short and long term CVC related S aureus bacteremia Crowley et al - Crit Care Med 2008; 36:385N=48, Thrombosis:71%Cure 23/34 (68%)Cure 12/14 (86%)

Trans-oesophagal echography and S.aureusn726** P < 0,0005Adapted from Fowler et al. JACC 1997

Malanovski GJ - Arch Intern Med 1995;155:1161Duration of treatment and complications: P=0.01S. aureus: Relapse increases if treatment is less than 10 days

S. aureus CRB : Short treatmentMeta-analysis 11 studies/ 132 PtsLate 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

Bactrimies sur KTEnlever KTATB 5 7 jKT en placeATB 10 14 j+/- verrouEnlever KTATB 14 jEnlever KTATB 10 14 jEnlever KTATB 14 japrs dernireHC +IDSA, CID, 2001InfectioncompliqueInfection non compliqueOter le KTATB prolonge4 8 semainesThrombophlbiteEndocarditeOstomyliteStaph coag negS.aureusBGNCandidaVoir pour ETO

Nothing!! Probably not justified in immunocompetent afebrile pt after CVC removal ? S. aureus (and P. aeruginosa) or immunosupression ?? (5-7d?)Duration of treatment proposals (Negative BC)

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, TaurolidineCVC use is impossible during the lockInjection 2 fold a day, for 2 to 3 weeksAssociated IV antimicrobials Contra-indications: fungal infections, neutropenia, thrombophlebitis, tunnelitis, septic shock

Verrou (VLA) ou AB IV

Problmes de dfinition des infectionsSites dinfection inconstamment citsParamtres dvaluation de lefficacit diffrents

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.

Arch Pediatr Adolesc Med. 2006;160:1049-1053Treatment 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

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-BuissonReanimation 2003

Bactrimies sur KTEnlever KTATB 5 7 jKT en placeATB 10 14 j+/- verrouEnlever KTATB 14 jEnlever KTATB 10 14 jEnlever KTATB 14 japrs dernireHC +IDSA, CID, 2001InfectioncompliqueInfection non compliqueOter le KTATB prolonge4 8 semainesThrombophlbiteEndocarditeOstomyliteStaph coag negS.aureusBGNCandidaVoir pour ETO

18Here is the MIC s of a slime producer Sraf epidermidis. For example the MIC of gentamycin was increased by more than a hundered fold in presence of slime. The MBCs of attached bacteria are also increased by a more than 128 fold.

Finaly CVC maintenance is always associated with an increased risk of failure in case of catheter-related sepsis . However in three forth of the cases, catheters are removed but innocent!!!Post hoc analysis of a randomized study comparing fluconazole and amphotericine BManagement of Central Venous Catheters in Patients with Cancer and Candidemia IssamRaad,1 HendHanna,1 MahaBoktour,1 EssamGirgawy,1 HadiDanawi,3 MasoudMardani,1 DimitriosKontoyiannis,1 RabihDarouiche,2 RayHachem,1 and GeraldP.Bodey1 1Department of Infectious Diseases, Infection Control and Employee Health, University of Texas M.D. Anderson Cancer Center, 2Baylor College of Medicine, and 3University of Texas School of Public Health, Houston To determine the need and appropriate timing of catheter removal in patients with candidemia, the records for 404 patients with cancer and central venous catheters (CVCs) who developed candidemia during the period of 1993 1998 were retrospectively reviewed. Of the total 404 cases of candidemia, 241 (60%) were due to a primary source, 111 (27%) were catheter related, and 52 (13%) were secondary cases of candidemia caused by a source other than the catheter. Multivariate analysis showed that catheter removal 72 h after onset improved response to antifungal therapy exclusively in patients with catheter-related candidemia (P = .04). Clinical characteristics that suggested a noncatheter source for the candidemia were disseminated infection (P < .01), previous chemotherapy (P < .01), previous corticosteroid therapy (P = .02), and poor response to antifungal therapy (P < .03). CVC removal 72 h after onset should be considered in patients with suspected catheter-related candidemia who have no evidence of dissemination, recent corticosteroid therapy, or chemotherapy.

Management of Central Venous Catheters in Patients with Cancer and Candidemia IssamRaad,1 HendHanna,1 MahaBoktour,1 EssamGirgawy,1 HadiDanawi,3 MasoudMardani,1 DimitriosKontoyiannis,1 RabihDarouiche,2 RayHachem,1 and GeraldP.Bodey1 1Department of Infectious Diseases, Infection Control and Employee Health, University of Texas M.D. Anderson Cancer Center, 2Baylor College of Medicine, and 3University of Texas School of Public Health, Houston To determine the need and appropriate timing of catheter removal in patients with candidemia, the records for 404 patients with cancer and central venous catheters (CVCs) who developed candidemia during the period of 1993 1998 were retrospectively reviewed. Of the total 404 cases of candidemia, 241 (60%) were due to a primary source, 111 (27%) were catheter related, and 52 (13%) were secondary cases of candidemia caused by a source other than the catheter. Multivariate analysis showed that catheter removal 72 h after onset improved response to antifungal therapy exclusively in patients with catheter-related candidemia (P = .04). Clinical characteristics that suggested a noncatheter source for the candidemia were disseminated infection (P < .01), previous chemotherapy (P < .01), previous corticosteroid therapy (P = .02), and poor response to antifungal therapy (P < .03). CVC removal 72 h after onset should be considered in patients with suspected catheter-related candidemia who have no evidence of dissemination, recent corticosteroid therapy, or chemotherapy.




Malanovski:Long-term (16) or short-term (34) CVCs

9 J1 il ny a que des microcoloniesLa technique mRNA permet de detecter les bactries encore viable et de les quantifier

Qualitative broth culture and quantitative culture on agar were compared with quantitative polymerase chain reaction (PCR) for thediagnosis of foreign body infections (FBI) in a rat model with and without exposure to systemic antibiotics (teicoplanin and rifampin). The3 methods had a similar and high yield without antibiotics. Antibiotics decreased the number of CFU/foreign body and increased the numberof culture-negative foreign bodies and the variability of the results in quantitative culture. The yield of broth culture remained high underantibiotics although prolonged incubation (2-5 days) was required. The yield of the PCR was equivalent or even superior (for teicoplanin)to the yield of broth culture. Quantitative PCR had a higher yield and lower variability than quantitative culture and was not affected byantibiotics. The simultaneous isolation of RNA from all samples indicated viability of the bacteria. Quantitative PCR seems a promisingmethod for the diagnosis of FBI.

10In the absence of severe sepsis, for exemple in case of fever without no evident cause which is a frequnet circumtance in the ICU, it shoud be interresting to perform diagnostic procedures without removing catheter

It should be known that a negative cutaneous swab culture is a strong argument for the absence of cathetr-related sepsis.

In this circumstance, paired peripheral and central blood culture with differential quantitative cultures of differential time to positivity is able to acurately make the diagnosis of CRS at least for long-term CVCs and oncologic patients.

216Sensibilisation de la technique grace la brosse endoluminaleClassification base sur la clinique et la culture du KT et la rgression lablation du KT34 paires sont prlev pour les 18 ayant une CR BSI et un couple dHC positive

23/34 seulement ont un couple dHC positif9 ont H+/P-, et 2 H-/P-donc, les H+/P- sont difficiles classerchez les patients avec plusieurs H+ P+ toutes donnent des delai de positivit sup 120 mnAbstract Objective: To find a subsetof patients with suspected centralvenous catheter (CVC)-related infection(CRI) in whom CVC removal isnot needed. Design: Randomizedcontrolled trial. Setting: Thirty-threebedICU. Patients and participants:One hundred and forty four patientswith suspected CRI in which a changeof CVCs was planned were evaluatedfor inclusion. Interventions: Hemodynamicallystable patients withoutproven bacteremia, no insertion siteinfection, and no intravascular foreignbody were randomized to astandard-of-care group (SOC, allCVCs were changed as planned) or awatchful waiting group (WW, CVCschanged when bacteremia was subsequentlyconfirmed or hemodynamicinstability occurred). Measurementand results: Study groups were comparedfor incidence of CVC-relatedbloodstream infection (CR-BSI), resolutionof fever, C-reactive protein,SOFA score, duration of ICU stay,and mortality. Of 144 patients withsuspected CRI, 80 patients met exclusioncriteria. Sixty-four were randomized.Forty-seven of 80 excludedpatients were shown to be bacteremic,20 (25%) of whom had aCR-BSI. Five of 64 (8%) includedpatients had a CR-BSI during theirsubsequent ICU stay (two in SOC andthree in WW group). All 38 CVCswere changed in the SOC groupversus 16 of 42 in the WW group(62% reduction, P0.1 for all).Conclusions: The use of a simpleclinical algorithm permits a substantialdecrease in the number of unnecessarilyremoved CVCs withoutincreased morbidity.

12182119Une analyse cas/temoin apparie sur provenance, charlson et age entre les 77expet 77 contrle ne trouve pas de dif de dc(9 vs 14%) mais 2 vs 9 bacteriemies dans les 3 mois (p=0.03) Pas de doppler, echo cardio non systematique

This retrospective cohort study examined theclinical significance of isolated Staphylococcusaureus central venous catheter (CVC) tip cultures(i.e., positive tip cultures without concomitantpositive blood cultures). Subsequent S. aureusbacteraemia was found in nine (12%) of 77patients at a median time of 4 days after CVCremoval. A high co-morbidity score and noeffective antibiotic treatment within 48 h of CVCremoval were independent risk-factors for septiccomplications following multivariate analysis. Amatched case-control study that compared theabove cohort with patients with CVC tip culturesnegative for S. aureus supported the significanceof these findings.

Une analyse cas/temoin apparie sur provenance, charlson et age entre les 77expet 77 contrle ne trouve pas de dif de dc(9 vs 14%) mais 2 vs 9 bacteriemies dans les 3 mois (p=0.03)

This retrospective cohort study examined theclinical significance of isolated Staphylococcusaureus central venous catheter (CVC) tip cultures(i.e., positive tip cultures without concomitantpositive blood cultures). Subsequent S. aureusbacteraemia was found in nine (12%) of 77patients at a median time of 4 days after CVCremoval. A high co-morbidity score and noeffective antibiotic treatment within 48 h of CVCremoval were independent risk-factors for septiccomplications following multivariate analysis. Amatched case-control study that compared theabove cohort with patients with CVC tip culturesnegative for S. aureus supported the significanceof these findings.

Patients with Staphylococcus aureus colonization of an intravascularcatheter but without demonstrated bacteremiawithin 24 h after intravascular catheter removal had a 24%(12 of 49 patients) chance of subsequent S. aureus bacteremiaif they did not receive immediate antistaphylococcal antibiotics.Treatment within 24 h after intravascular catheterremoval led to a 83% reduction in the incidence of subsequentbacteremia.

Patients with Staphylococcus aureus colonization of an intravascularcatheter but without demonstrated bacteremiawithin 24 h after intravascular catheter removal had a 24%(12 of 49 patients) chance of subsequent S. aureus bacteremiaif they did not receive immediate antistaphylococcal antibiotics.Treatment within 24 h after intravascular catheterremoval led to a 83% reduction in the incidence of subsequentbacteremia.

We believe that patients with S. aureus in IVC tip cultures are colonised, possibly at multiplesites. Therefore, they are at high risk for subsequent infection when compared with noncolonisedsubjects. Whether isolating S. aureus from an IVC tip without any sign of infection predictsa higher risk for subsequent bacteraemia, and whether antibiotics decrease this probability,needs to be clarified.

Abstract Purpose: To assess the influence of antifungal therapy on theoutcome of non-candidemic adult patients with central vascular catheter(CVC) tips colonized by Candida species. Methods: A retrospectiveanalysis of the outcome of patientswith Candida colonization of theirCVC tip and no concurrent candidemiawas made over a 4-year period.Patients who either died or developedcandidemia-invasive candidiasis(poor outcome) were compared withthose who improved. Results: Wefinally included 58 patients for analysis.Almost all (91.4%) had to beadmitted to the ICU during theirhospital stay. Independent predictorsfor outcome were a McCabe andJackson score corresponding to ultimatelyfatal underlying disease [oddsratio (OR) 11.98; 95% confidenceinterval (CI), 1.37104.97;P = 0.02], and maximum severitycorresponding to severe sepsis, septicshock or multiorgan failure (OR:6.16, CI 95%: 1.0037.93; P = 0.05).We were unable to demonstrate thatantifungal therapy was an independentvariable influencing outcome(OR 0.82; 95% CI, 0.272.47;P = 0.73). Conclusions: Our datasuggest that, in non-neutropenic criticallyill patients with no concomitantcandidemia and with CVC tips colonizedby Candida, antifungal therapydoes not seem to have a significantinfluence on clinical outcome.

2128Caspo kills > 99of sessile cells within the biofilm at attainable concentrationsProbably because the fungal cell wall is one of the component of the candidal biofilm and the target of this new agent (blocking of the 1,3 B D glucan).

Figure: biofilms is less hyphal and some of the cells within the biofilms presented abberrant morphologiesRed fluorescence characterize metabolic activities .treated biofilm with 0.5 g/ml of caspofungin showed a diffuse green fluorecence characteristics of dead cells225There is growing concern that vancomycin has diminished activity for methicillin-resistant Staphylococcusaureus (MRSA) infections, with vancomycin MICs at the high end of the CLSI susceptibility range. Despite thisgrowing concern, there are limited clinical data to support this notion. To better elucidate this, a retrospectivecohort study was conducted among patients with MRSA bloodstream infections who were treated with vancomycinbetween January 2005 and May 2007. The inclusion criteria were as follows: at least 18 years old,nonneutropenic, with an MRSA culture that met the CDC criteria for bloodstream infection, had receivedvancomycin therapy within 48 h of the index blood culture, and survived >24 h after vancomycin administration.Failure was defined as 30-day mortality, bacteremia >10 days on vancomycin therapy, or a recurrence ofMRSA bacteremia within 60 days of vancomycin discontinuation. Classification and regression tree (CART)analysis identified the vancomycin MIC breakpoint associated with an increased probability of failure. Duringthe study period, 92 patients met the inclusion criteria. The vancomycin MIC breakpoint derived by CARTanalysis was >1.5 mg/liter. The 66 patients with vancomycin MICs of >1.5 mg/liter had a 2.4-fold increase infailure compared to patients with MICs of 1.5 mg/liter was independently associated with failure (adjustedrisk ratio, 2.6; 95% confidence interval, 1.3 to 5.4; P 0.01). These data strongly suggest that patients withMRSA bloodstream infections with vancomycin MICs of >1.5 mg/liter respond poorly to vancomycin. Alternativeanti-MRSA therapies should be considered for these patients.

Analyse de sous groupe du papier de Fowler

Objectives: In a prospective, randomized trial, daptomycin was non-inferior to standard therapy forStaphylococcus aureus bacteraemia and right-sided endocarditis. Since rates of infection due tomethicillin-resistant S. aureus (MRSA) infection are increasing and treatment outcomes for bacteraemiacaused by MRSA are generally worse than those observed with methicillin-susceptible S. aureus bacteraemia,clinical characteristics and treatment results in the trials pre-specified subset of patientswith MRSA were analysed.Methods: Clinical characteristics and outcomes of patients receiving daptomycin were compared withthose receiving vancomycin plus low-dose gentamicin. Success was defined as clinical improvementwith clearance of bacteraemia among patients who completed adequate therapy, received no potentiallyeffective non-study antibiotics and had negative blood cultures 6 weeks after end of therapy.Results: Twenty of the 45 (44.4%) daptomycin patients and 14 of the 43 (32.6%) vancomycin/gentamicinpatients were successfully treated (difference 11.9%; confidence interval 28.3 to 32.1). Success ratesfor daptomycin versus vancomycin/gentamicin were 45% versus 27% in complicated bacteraemia, 60%versus 45% in uncomplicated bacteraemia and 50% versus 50% in right-sided MRSA endocarditis.Cure rates in patients with septic emboli and in patients who received pre-enrolment vancomycin weresimilar between treatment groups. However, in both treatment groups, success rates were lower in theelderly (75 years). Persisting or relapsing bacteraemia occurred in 27% of daptomycin and 21% ofvancomycin/gentamicin patients; among these patients, MICs of 2 mg/L occurred in five daptomycinand four vancomycin/gentamicin patients. The clinical course of several patients may have been influencedby lack of surgical intervention.Conclusions: Daptomycin was an effective alternative to vancomycin/gentamicin for MRSA bacteraemiaor right-sided endocarditis.

Taux de vanco med 14.7 mg/l

23Objective: Infection and thrombosis are important complicationsof intravascular catheters. The purpose of this study was todetermine the incidence of thrombosis in patients with centralvenous catheterassociated Staphylococcus aureus bacteremiaand the utility of physical examination for diagnosing upperextremity or neck venous thrombosis.Design: Prospective observational cohort.Setting: Tertiary care facility.Patients: In all, 65 consecutive patients with catheter-associatedS. aureus bacteremia with central venous catheters of theinternal jugular, brachial, or subclavian veins were eligible forparticipation.Intervention: From July 1999 through August 2004, enrolledpatients underwent physical examination and ultrasonographyindependently to identify the presence of catheter-associatedthrombosis. Study ultrasonograms were interpreted blindly usingdefined criteria. Outcomes were defined at 12-wk follow-up.Measurements and Main Results: A total of 48 patients wereenrolled. By ultrasonography, definite or possible thrombosis waspresent in 34 of 48 patients (71%) in this cohort. Death orrecurrent bacteremia occurred in 11/34 (32%) infected patientswith thrombosis and two of 14 (14%) infected patients withoutthrombosis (p .29). Sensitivity of all physical examinationfindings, either alone or in combination, was low (

Conduite à tenir devant une suspicion d’infection liée aux cathéters en réanimation

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