1. Risk factors for long-term catheter-related infections Jean-François TIMSIT Medical ICU Epidemiology, INSERM U 578 ESICM Barcelona – Sept 25th 2006

2. Routes of catheter contamination Extraluminal: Skin infection: Hematogenous seeding Endoluminal: Hub contamination Infusate contamination

3. Skin vs. hub originated CRS Long-term catheter-related infection are mainly hub-related Guidet (1994) Fan et al. (1988) Cicco et al. (1989) Liñares (1985) Salzman (1993) Weightman (1988) CATH TIME 7 15 18 21 24 110 65% 35% 50% 10% 30% 35% 25% 50% 70% SKINHUB

4. –Cuffed tunneled, silicone rubber elastomer catheters (Hickman type) Frequent access –Totally implanted venous access ports Mainly intermittent use Many more data for short-term CRI Long-term hemodialysis CVCs

5. Main risk factors Time Type of devices Rank of the device Underlying illness Handling  specialized team, education Thrombosis  anticoagulants and fibrinolytics Potential for the use of antiseptic and antimicrobials??

6. CRS and catheterization time 0 10 20 30 40 50 60 70802,557,51012,51517,52022,525 Catheter days Prevalence of CRS Sitges-Serra A 1988

7. Rate of BSI are different according to the type of devices… Crnich CJ & Maki DG – Clin Infect Dis 2002; 34:1362

8. Influence of the Rank of the catheter Nephrol Dial transplant 2001; 16:2194 573 CVCs, 336 patients, half-life 312 days 1 episode of CRS per 25.6 Pts months

9. Astagneau P et al – ICHE 1999; 20:494 10-month (1995) Prospective follow-up, 12 hospitals, Paris Hickman CVCs and Ports Cancer (n=255) and HIV (n=201) infected patients 3.78 vs 0,39 per 1000 CVC-days, p<0.001 HIV Cancer HIV > Cancer

10. Groeger et al - Ann Intern Med 1993 Hematologic malignancies > solid tumors

11. Risk factor of CRI in onco-hematology: the major role of neutropenia hosp vs home therapy Neutropenia Risk factors New CVC 1,3 0,4 - 3,8 6/2732 7/4100 6/1259 0/1473 15,1 2,6 - 86,5 RR IC 95% Nb CRI / nb of devices days 3/1118 3/1614 1,4 0,3 - 7,1 TPN 0/499 3/1525 0,4 0,0 - 69,4 ARA - C 3/981 0/378 2,7 0,9 - 8,3 BMT 3/708 3/2024 2,9 0,6 - 13,1 Howell PB et al Cancer 1995; 75 : 1367-75 Howell PB et al Cancer 1995; 75 : 1367-75

12. Risk factors for BMT recipients Univariately: More septicemia during neutropenic than non neutropenic days 17.82 vs 5.51 per 1000 catheter days Cox’s model: –Age > 18y: RR=2.03, p=0.003 –Presence of VOD: RR=1.65, p=0.028 81/242 BMT recipients with 100 episodes of CR infections Propective follow up, during the hospitalisation (7 to 187 days) Cox model, neutropenia as a time-dependant covariate Elishoov H et al - Medicine. 1998 Mar;77(2):83-101.

13. Ann Intern Med 1999; 131:340 215 Hickman, 125 Cook, 324 PICC,155 Midline, 70 Ports 69532 device days (1 to 395, med 44) Rate of infection: 0.99/1000 cvc days (*) outpatient clinics or physician’s office *

14. Frequency of CVC handling HIV 3.04/1000 cvc-days  20-40% days in use 5.07/1000 cvc-days  80-100% days in use Cancer patients 0.17/1000 cvc-days  0-20% days in use 4.9 /1000 cvc-days  60-80% days in use Astagneau P et al – ICHE 1999; 20:494

15. Change of the CVC extension set or the dressing more than once a week HIV infected patients Change of CVC extension more than once per week: –4.8 vs 2.61/1000 CVC-days, p=0.03 Change of dressings more than once per week: –4.6 vs 2.54/ 1000 CVC-days, p=0.04 Astagneau P et al – ICHE 1999; 20:494

16. Prevention of CRS Impact of catheter care teams on the rate of catheter-related sepsis CRS rate before (%) after (%) Freeman (1972) 212.3 Sanders (1976) 28.64.7 Stotter (1987) 398 Kehoane (1983) 334 Tomford (1984) 2.10.2 Faubion (1986) 243.5 Nelson (1986) 28.83.3

17. Patient education Moller T et la - Journal Hosp. Infect (2005) 61, 330–341 82 tunneled Hickman cath., hematology Individualized training vs control –General information –Pratical guidance in principles and techniques –Controlled testing of the patients’ theoretical knowledge and behavior –3 modules: sterile dressing + flushing techniques + drawing blood samples

18. Relationship between thrombosis and infection Post-mortem study: long term catheter – Thrombus of the vein wall in 38% of catheterized veins –7/31 patients with thombosis have had a CR-BSI –0/41 patients with a normal catheterized vein have developped CR-BSI Raad - JAMA 1994; 271:1014

19. Continuous infusion of low dose Unfractionated heparin in Patients with onco-hematologic diseases UH: 100 U/Kg/dys vs Saline Subclavian, investigator blinded 210 eligible/ 204 included Abdelkefi et al – J Clin Oncol 2005; 23:7864 Heparin (102)Control (102)P value Duration of cvc27 (8-81)26 (8-74).1 Reason for removal End of treatment CRThrombosis CRBI 84 2 7 65 10 17.03 Stem cell transplant 8281.2 PTN Abx Blood Asparaginase 62 85 82 5 54 72 70 6.6 Thrombosis: 2 vs10, p=0.017 CR-BSI: 7 vs 17, p=0.03 (4.2 vs 2.5/1000 dys)

20. Urokinase lock in pediatric oncologic patients Dillon et al - J Clin Oncol. 2004;22(13):2718-23 577 patients, 29 centers 281 ports, 288 external CVCs (86% bi- lumen) Stratified allocation, unblind Urokinase 5000 IU at least 1 hour/2 weeks + heparin vs heparin alone  Rate of occlusive events Rate of infections 1.6 vs 2.2 CR-BSI, p=0.07, logrank test Occlusive events 23% v 31%, P.006 Ports 2.6 vs 3.9 / 1000 CVCs days External cath.

21. Thrombolysis Urokinase > 5000 IU every 1-2 or 3-4 weeks Reduced incidence of thrombosis Reduced the incidence of premature IVD loss Tendency of benefit to reduce CR-BSI Cost-benefit analysis? Adapted From Ray CE 1999, Dillon 2004, Solomon 200, Aquino 2002

22. MRSA carriage at insertion No Nasal SA (58) No nasal SA (31) Age6858.6** Peripheral atherosclerosis 15.5%39%* History of bact.40%65% Months on dialysis6259 End of the study CVC surv.482720* Nb of bacteremia0.2  0.61.6  1.6*** Bacteremic patients 12%80%*** Local infect.12%65% Jean G et al – Nephron 2002; 91:399 * p<0.05 **p<0.001 ***p<0.0001

23. Mupirocin.(meta-analysis).is effective.. But emergence of resistant strains is frequent Taconelli et al- 2003;37:1629-1638

24. In vitro efficacy of Taurolidine-citrate solution Shah CB et al – AAC 2002; 46:1674

25. Taurolidine + citrate vs Heparin

26. Antibiotic lock therapy 117 Long-term CVCs Hematologic patients with neutropenia 10 UI/ml of heparin + 25µg/ml de Vanco 1 heure/2 days Carratala AAC 1999; 43:2200 Potential ecological impact

27. Ab lock therapy Henrickson 2000; J Clin Oncol 18:1269-1278 =Vanco+heparin=Vanco+heparin+cipro

28. Long-term Abx impregnated vs cuffed tunneled CVC Darrouiche RO et al – Ann Surg 2005; 242:193  Rafael Sierra…