Treatment of catheter-related contaminations

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Treatment of catheter-related contaminations Jean-François TIMSIT CHU Albert Michallon Université Joseph Fourrier, INSERM U578, Grenoble France Slides accessible on http://www.outcomerea.org

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Epidemiology of catheter-related bacteremia in HD patients Allon M – Am J Kidney Dis – 2004; 44:779

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Epidemiology of catheter-related bacteremia in HD patients Allon M – Am J Kidney Dis – 2004; 44:779 25% of the 300,000 US HD patients 2-overlap: disease related hospitalization and demise 2.5 to 5.5 cases/1000 pts days = 0.9 to 2 scenes/understanding year  67,500 to 150,000 scenes/year  10%= 7,000 to 15,000 with genuine confusions

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CR-Infection in HD patients 11.7% of septicemia in HD pts Temporary uncuffed cath. 1.6 to 7.7 bacteremias/1000 catheter-days Tunneled or handcuffed cath. 0.2 to 0.5 bacteremias/1000 catheter-days Staphylococci coag neg. 40-77%, methicillin safe 40-75% Enterococci, gram neg pole. Metastatic complexities: 8.7 to half (med 25%) Studies Microbes  handcuffed cath. Peleman et al – Nephrol dial transplant 2000; 15:1281

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Complications connected with handcuffed HD Cath. Nephrol Dial transplant 2001; 16:2194 1 scene of CRS for every 25.6 Pts months 24% in the principal addition week

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CR-Infection in HD patients

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Contamination From the center Cross sullying Cutaneous vegetation Extral uminal cutaneous Colonization SKIN VEIN Hematogeneous Colonization M echanisms of colonization From Maki DG et coll., in "Hospital Infections", Bennett JE & Brachman PS, 1992, 849-98.

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Extraluminal Colonization Short term CVCs Colonization Of the endoluminal surface Long term CVCs Slime

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Predisposing elements

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Spectrum of CRBSI related bacterial greenery Saxena AK et al – Swiss Med Wkly 2005; 135:127

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Spectrum of CRBSI related bacterial verdure

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CRS : The treatment is relying upon the Severity of the sepsis Underlying ailment (immunosuppression, prothesis). Small scale creatures recognized or associated Results with the blood societies (positive or not). Need and ease of a focal venous get to

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CRS: What ought to be the inquiries? What ought to be finished with the CVC? Should we endorse systemic antimicrobials ? In the event that Yes, which one? What ought to be done if there should arise an occurrence of disappointment ? What ought to be the span of treatment ?

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What ought to be finished with the CVC? Should we recommend systemic antimicrobials ? In the event that Yes, which one? What ought to be done if there should be an occurrence of disappointment ? What ought to be the span of treatment ?

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What ought to be finished with the catheter ? Two requirements : To maintain a strategic distance from pointless evacuation of CVCs (75% cases) and further dangers of catheter addition  To spare patients and stay away from entanglements of contamination

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CRB finding in HD patients 59-81% of HD patients with fever or chills have positive BC ¾ identified with CRI (pneumonia, foot diseases) Use DTP techniques (???) When? before dialysis session, amid the session? BC by means of fringe vein regularly troublesome (39%) Significance of a positive BC through the cath. Lumen? Bacteriologic assessment in detached HD units? Grouping framework: Definite: C/P quantitative BC> 10 Probable: Positive BC and no proof of different irresistible site Possible: neg BC and determination of fever at CVC expulsion

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Severe sepsis of obscure starting point Catheter evacuation (or Guidewire trade) Which antimicrobials? How to analyze entanglements? Fever, chills without serious sepsis Positive blood culture Is it conceivable to keep the CVC without dangers? 2 circumstances

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Type et rate of extreme intricacies (n = 102) Shock Sepsis Thrmb. Sept. Other Total (%)* CNS 3 1 6/33 (18) S. aureus 3 3 4 8 12/32 (38) Enterococci 0 0 0/3 GNB 2 0 2/10 (20) P.aeruginosa 1 0 1 0 2/4 (50) Candida spp. 0 7 0 7/11 (64) Polymicrob. 2 1 0 4/9 (44) * Nb Complications/Nb of occasions Arnow PM et al. 1993 Clin Infect Dis

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Is catheter expulsion connected with a higher cure rate and with an enhanced result?

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The Slime… Slime creation (SCN) 24h cellulose (x 5000) SCN culture

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MICs (10 7 cfu/ml) (mg/l) MH Slime 1.56 6.25 4 6.25 >100 >32 0.19 12.5 64 1.56 25 16 0.79 >100 >126 0.79 25 32 CNS-Carsenti-Etesse 2000 Oxacillin Vancomycin Clindamycin Ciprofloxacin Gentamicin Netilmicin MBC of connected microorganisms expanded by 128-256 overlay 1-Bacterias with ooze generation have an expanded MICs and MBCs to ABt 2-The Biofilm increment the resistance of microscopic organisms to ABt

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Catheter expulsion and span of candidemia Rex et al - Decrease of the length of the candidemia New site 5.6 days versus Other 2.6 days - Bias: APACHE II 14.5 versus 16.9 p=0.03 Other catheter: 1.2 versus 1.8,p<0.001 - GWX : 6.3 + 1.8 j Catheter evacuation ought to be prefered

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Candidemia: CVC Removal and mortality Nguyen et al - Arch Intern Med 1995;155:2429 427 back to back patients with candidemia Multicentric imminent study Mortality KT expelled: 21% versus KT set up: 41% p<0.001 Microbio disappointment (multivariate examination) Neutropenia 0.002 Intra-abdo 0.02 KT left in place 0.05 Mortality (multivariate investigation) ICU patients <0.001 Age > 60 y 0.004 Steroïds 0.02 Candidal pneumonic metastasis <0.001 KT left in place <0.001

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Candidemia: CVC evacuation and mortality: meta-investigation 4 concentrates on with seriousness scores conformity Anaissie 1998 (n=491) Retro adjusted OR: 2 (1.4-2.9, p=0.06) Nucci 1998 (n=54) Pro adjusted OR: Nucci (2) 1998 (n=145) Pro adjusted OR: 4.22 (2-11.6) Luzzatti 2000 (n=189) retro adjusted OR: 1.61 (1.01-2.63, p=0.047) Analyses are one-sided in light of the fact that CVCs expulsion is connected with seriousness… Nucci – Clin Infect dis 2002; 34:591

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Management of CVCs in patients with disease and candidemia Raad I et al – Clin Infect Dis 2004; 38:1119 1993-1998: 404 scenes of candidemia (half ICU) with 1 CVCs for over 1 days 3 classifications Primary candidemia : 241 (60%) Secondary candidemia: 52 (13%) CVC related candidemia : 111 (27%) + tip clique (66) or quantitative BC > 5:1 (45) %

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Is candidemia catheter-related? Raad I et al – Clin Infect Dis 2004; 38:1119 111 catheter-related candidemia and 52 auxiliary candidemia No CS inside 1 month: OR 3.5 (1.3-9.4), p=0.02 No chemotherapy inside 1 month: OR 4.3 (1.5-13.3), p<0.01 Non dispersed contamination * OR 9.7 (3.5-26.3), p<0.01 Good reaction to antifungal therapy* OR 2.9 (2.2-7.2), p=0.03 (*) Dissemination to non coterminous destinations Resolution of fever and chills, BC neg.

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

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Predictors of inability to react to antifungal treatment Raad I et al – Clin Infect Dis 2004; 38:1119

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

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Biofilm generation and antifungal impacts 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 eichinocandins (caspofungin) 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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Fungal biofilm and medication resistance Mechanism not totally comprehended Biofilm cells oppose > planktonic cells? Part of few persisters cells Grew gradually within the sight of antimicrobials, A specific imperviousness to program cell demise (apoptosis) prompted by antimicrobials?

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S. aureus bacteremia: Catheter evacuation? 50 CRB (review) Long-term (16) or short-term (34) CVCs % P=0.01 Malanovski GJ - Arch Intern Med 1995;155:1161

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65 S. aureus bacteremia in HD patients Marr et al – Kidney Int 1998; 54:1684

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Absence of catheter evacuation is an autonomous indicator of treatment disappointment in Catheter-related-S aureus bacteremia Fowler et al – Clin Infect Dis 1998; 27:478 244 patients Advices by the irresistible ailments division 12-month follow up Advice took after: 112 pts (49.5%) Perform TEE, expelled tainted intravascular gadgets, perform reconnaissance BC, utilize beta-lactam as regularly as could be allowed (MSSA)

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HD is essentially connected with hematogeneous entanglements (multivariate examination) Fowler et al – Clin Infect Dis 2005; 40:695

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In vivo biofilm-bacterial killing Wilcox MH et al – J antimicrob Chemother 2001; 47:171 50 µl blood: acridine orange Gram pos HD biofilm + quantitative state check (100 µl of blood) HD cath expelled : VAN 1g 2 hours and afterward 10 ml flush of 0.9% saline Endoluminal biofilm recuperated utilizing uncommon brushes Eradication failed+++ Uge variety of biofilm VAN level (0.2-89 mg/g!!) Reduction of 84-100% bacterial tally (med 95%) with VAN and Reduction of 0-98% (med 91%) with LNZ

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LNZ, VAN, GEN, eperezolid in vitro S. epidermidis catheter-related biofilm contaminations Curtin J et al – Antimicrob Agent Chemother 2003; 47:3145 Biofilm: altered rubbins gadget 12 examining ports of 50 mm 2 + SE ATCC 35984 + persistent stream of MH soup 24 hours + 24 hours of clean MH stock nourishing AB bolt of VAN (10mg/ml),LNZ (4),GEN (10),EPZ (2mg/ml) 24, 72, 168 and 240 hours

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149 Patients with bacteremia (Pseudomonas spp et Xanthomonas) Elting et al - Medicine 1990;69:296 % P<0.00001 49/49 4/4 32/62 2/6

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Coagulase negative staphylococci Raad et al ICHE 1992

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