TauroLock Prospekt ENG

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ANTIMICROBIAL CATHETER LOCK SYSTEM TO PROVIDE PATENCY AND INFECTION CONTROL

Prophylaxis against catheter related bloodstream infections:

Prophylaxis against biolog­ical occlusion in the catheter:

Central venous catheters (CVC) are used as short or long term vascular access devices in haemo-dia­lysis, oncology, ICU and total parenteral nutrition. High risks for CVC malfunction are catheter-related infections (CRI). These infections may be triggered by microbial colonisation of the catheter from which the microorganisms can spread into the bloodstream. CRI may develop septic symptoms which would require the immediate removal of the catheter.

TauroPharm catheter lock products provide a threefold prophylaxis against occlusion in the catheter.

TauroPharm catheter lock solutions were developed for prophylactic use to reduce catheter-related infections. The antimicrobial activity of TauroLock™/ NutriLock™ is based on taurolidine which is bactericidal, including against resistant bacteria such as MRSA and VRE, as well as fungicidal. TauroLock™/ NutriLock™ do not contain any antibiotics.

CDC and ERBP demand the use of antimicrobial lock solutions such as TauroLock™ which is recommended by various national guidelines in dialysis, oncology and parenteral nutrition (see literature 1).

All TauroLock™ solutions contain 4% citrate as an anticoagulant. This concentration removes calcium safely and effectively from the clotting cascade.

Based on one randomised study TauroLock™ increases the need for thrombolytic treatment vs. heparin 5.000 IU/ml in dialysis patients (Lit. 2.3).

Therefore, we recommend TauroLock™-HEP500 as standard lock solution in dialysis which is comparable to heparin regarding patency (Lit. 2.4). The optional use of low concentrated heparin supports an anticoagulative effect via binding to antithrombin.

The combination of TauroLock™-HEP500 and TauroLock™-U25.000 (which contains urokinase) in a 2+1 protocol is a further regimen which significantly reduces patency problems in two randomised studies versus citrate 4% (p=0.006, Winnicki et al, Lit. 2.7) or TauroLock™-HEP500 (p=0.004**, Al-Ali et al, Lit. 5.4).

TauroLock™-HEP100/500, TauroLock™-­­U25.000 and NutriLock™ have successfully been used in regimens to reduce catheter related infections.

TauroLock™ points to a trend to reduce (all cause) bloodstream infections (Lit. 2.3) and significantly reduces catheter related bloodstream infections in pediatric oncology (Lit. 3.1 and 3.2).

PAEDIATRIC ONCOLOGY

PARENTERAL NUTRITION

DIALYSIS

Field

Infection rate (per 1000 catheter days)

Product

Evidence level*/ p-Value / Literature

2,7 0,67

Citrate 4% TauroLock™-HEP500 (2x) / TauroLock™-U25.000 (1x)

1B / p=0.003 / Winnicki et al. (Lit. 2.7)

1,08 0,04

Heparin 5000 IU/mL TauroLock™-HEP500

2B / p=0.023 / Fontseré et al. (Lit. 2.6)

1,59 0,69

Heparin 5000 IU/mL TauroLock™-HEP500

2B / p=0.004 / Murray et al. (Lit. 2.5)

2,4 1,4

Heparin 5000 IU/mL TauroLock™

1B / p=0.1 / Solomon et al (2010, Lit. 2.3)

3,25 1,33

Heparin 5000 IU/mL TauroLock™-HEP500

2B / p=0.001 / Solomon et al (2012, Lit. 2.4)

1,0 0,0

Heparin 100 IU/mL TauroLock™-HEP100

1B / p=0.005 / Tribler et al (Lit. 4.3)

1,44 0,33

Saline 0.9% NutriLock™ (citrate free, 2% Taurolidine)

1B / p=0.002 / Wouters et al (Lit. 4.2)

6,58 1,09

Saline 0.9% TauroLock™

2B / p<0.001 / Touré et al (Lit. 4.1)

1,4 0,4

Heparin 100 IU/mL TauroLock™-HEP100

1B / p=0.001 / Handrup et al (Lit. 3.3)

1,3 0,3

Heparin 100 IU/mL TauroLock™

1B / p=0.03 / Dümichen et al (Lit. 3.2)

2,3 0,5

Heparin 200 IU/mL TauroLock™

2B / p=0.004 / Simon et al (Lit. 3.1)

Heparin 4% Citrate Saline NutriLock™ TauroLock™ or variant

* acc. to criteria from the center of evidence based medicine ** secondary endpoint with no previous sample size calculation

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TauroLockâ&#x201E;˘ is bactericidal and fungicidal within 2 hours: **

10

10

log cfu/mL

**

log cfu/mL

Legend

*detection limit (10 cfu/mL); **own data; *** Superior antimicrobial activity of trisodium citrate over heparin for catheter locking. Weijmer MC, Debets-Ossenkopp YJ, van de Vondervoort FJ, ter Wee PM, Nephrol. Dial.

Transplant . 2002,17:2189-2195

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1

2

3

4

24

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Time in hours

1

2

3

4

24

4

24

Time in hours

For comparison: Activity of Citrate 30% and Heparin Heparin ***

10

10

log cfu/mL

log cfu/mL

Citrate 30% **

0

Time in days

1

2

3

Time in hours

Catheter surface may be colonised by biofilm forming viable organisms.

Catheter surface without colonisation.

Catheter surface completely covered with S. epidermidis biofilm.

TauroLock™ and NutriLock™ are clinically safe: TauroLock™ (including its variants) and NutriLock™ have demonstrated good biocompatibility.

The concentration of 4% citrate in all TauroLock™ variants is safe and efficient according to the recommendation of the FDA (ref.: FDA Warning Letter, April 2000).

No fatal life threatening hypocalcaemic effects (e.g. cardiac arrest*) are reported for 4% citrate as used in TauroLock™ (in opposite to highly concentrated citrate solutions).** In this concentration, the citrate content (4%) used in TauroLock™ does not induce protein precipitation which can potentially cause embolism.*** NutriLock™ is citrate-free. * Cardiac arrest following injection of concentrated trisodium citrate. Punt CD, Boer WE. Clin Nephrol. 2008 Apr;69(4):317-8 ** Risks related to catheter locking solutions containing concentrated citrate. Hans-Dietrich Polaschegg, Klaus Sodemann. Nephrol.Dial.Transplant. 2003,18(12):2688-90 *** Embolic complications from central venous hemodialysis catheters used with hypertonic citrate locking solution. Willicombe MK, Vernon K, Davenport A. Am J Kidney Dis. 2010;55(2):348-51 Trisodium citrate induced protein precipitation in haemodialysis catheters might cause pulmonary embolism. Schilcher G, Scharnagl H, Horina JH, Ribitsch W, Rosenkranz AR, Stojakovic T, Polaschegg HD. Nephrol Dial Transplant. 2012;27(7):2953-7

Instillation of TauroLock™/NutriLock™ Follow the manufacturer’s instructions that accompany the particular venous vascular access product utilised. Specific catheter lock volumes are associated with each device.

1. Flush the device with 10 mL of saline.

2. Withdraw TauroLock™/NutriLock™ from the container using an appropriate syringe.

3. Instill TauroLock™/NutriLock™ slowly (not more than 1 mL per second, infants and children less than two years of age not more than 1 mL per 5 seconds) into the access device in a quantity sufficient to fill the lumen completely. Consult the manufacturer’s instructions for the specific fill volume or specify fill volume during implantation. This volume has to be strictly respected. TauroLock™/NutriLock™ will remain inside the access device until the next treatment (up to a maximum of 30 days).

4. Prior to the next treatment TauroLock™/NutriLock™ must be aspirated.

5. Flush the device with 10 mL of saline.

Product selection for field of application Product Dialysis Oncology Parenteral Nutrition

TauroLock™/NutriLock™ catheter lock solutions are available in different containers: Product Ampoule (10 x 3 mL) Ampoule (10 x 5 mL) Vial (100 x 10 mL) Vial (5 x 5 mL)

Manufacturer:

TauroPharm GmbH August-Bebel-Straße 51 D-97297 Waldbüttelbrunn Tel.: +49 931 304299-0 Fax: +49 931 304299-29

ISO 13485 85100/39/18

1. GUIDELINES AND RECOMMENDATIONS 1.1 Guidelines for the Prevention of Intravascular Catheter-related Infections CDC, Center of Disease Control, USA, 2011 1.2 Prévention des infections associées aux chambres à cathéter implantables pour accès veineux. SF2H. Hygienes 2012;Volume:92.

1.3 KRINKO Prevention of infections, which originate from blood vessel catheters. Koch-Institut KfKuIKbR. Bundesgesundheitsblatt 2017; Volume:36.

1.4 Diagnosis, prevention and treatment of haemodialysis catheter-related bloodstream infections (CRBSI): a position statement of European Renal Best Practice (ERBP) Vanholder R, Canaud B, Fluck R, Jadoul M, Labriola L, Marti-Monros A, Tordoir J, Van Biesen W. NDT Plus 2010;3(3):234-246.

1.5 Clinical Practice Guidelines for vascular access - Guideline 7. Prevention and Treatment of Catheter and Port Complications.

KDOQI NKF-. National Kidney Foundation - KDOQI 2006.

1.6 Clinical Practice Guideline - Vascular Access for Haemodialysis. Kumwenda M, Mitra S, Reid C. 6th Edition 2015.

1.7 Hygiene Guidelines 2008 (suppl. German Dialysis Standard). Deutsche Arbeitsgemeinschaft für Klinische Nephrologie e.V., Verband Deutscher Nierenzentren der DD nÄ e.V., (APN) AfPN. Deutsche Arbeitsgemeinschaft für Klinische Nephrologie e.V. 2006;Volume:121-184.

1.8 Evidence-based criteria for the choice and the clinical use of the most appropriate lock solutions for central venous catheters (excluding dialysis catheters): a GAVeCeLT consensus. Pittiruti M, Bertoglio S, Scoppettuolo G, Biffi R, Lamperti M, Dal Molin A, Panocchia N, Petrosillo N, Venditti M, Rigo C, DeLutio E. J Vasc Access 2016;17(6):453-464.

1.9 Evidence-based recommendations for the use of permanent CVADs in oncological paediatrics. Simon A, Beutel K, Hasan C, Bode U. GPOH 2013.

1.10 ESPEN guidelines on chronic intestinal failure in adults. Pironi L, Arends J, Bozzetti F, Cuerda C, Gillanders L, Jeppesen PB, Joly F, Kelly D, Lal S, Staun M, Szczepanek K, Van Gossum A, Wanten G, Schneider SM. Clin Nutr 2016;35(2):247-307.

1.11 S3-Guideline of the Deutsche Gesellschaft für Ernährungsmedizin e.V. in Cooperation with AKE, GESKES and DGVS. Lamprecht G, Pape UF, Witte M, Pascher A, und das DSC. Klinische Ernährung in der Gastroenterologie (Teil 3) – Chronisches Darmversagen 2014;Volume:e57-e71.

2. PUBLICATIONS: PROPHYLAXIS OF INFECTION IN DIALYSIS 2.1 Prophylaxis against Dialysis Catheter-Related Bacteraemia with a Novel Antimicrobial Lock Solution. M. Allon, Clin. Infect Dis 2003, 36:1539-1544.

2.2 Prevention of dialysis catheter-related sepsis with a citrate-taurolidine-containing lock solution.

Betjes MG, van Agteren M. Nephrol Dial Transplant 2004;19(6):1546-1551.

2.3 A Randomized Double-Blind Controlled Trial of Taurolidine-Citrate Catheter Locks (vs. Heparin (5000 IU/mL) for the Prevention of Bacteremia in Patients Treated With Hemodialysis. L. R. Solomon, J. S. Cheesbrough, L. Ebah, T. Al-Sayed, M. Heap, N. Millband, D. Waterhouse, S. Mitra, A. Curry, R. Saxena, R. Bhat, M. Schulz, P. Diggle, American Journal of Kidney Disease, 2010; Vol 55, No 6, 1060 - 1068.

2.4 Observational Study of Need for Thrombolytic Therapy and Incidence of Bacteremia using Taurolidine-Citrate-HEParin (TCH), Taurolidine-Citrate (TC) and Heparin Catheter Locks in Patients Treated with Hemodialysis. L. R. Solomon, J. S. Cheesbrough, R. Bhargava, N. Mitsides, M. Heap, G. Green, P. Diggle, Sem Dial 2012;25(2):233-8.

2.5 Taurolidine-citrate-heparin catheter lock solution reduces staphylococcal bacteraemia rates in haemodialysis patients.

E.C. Murray, C. Deighan, C. Geddes, P.C. Thomson, QJM.2014;107(12):995-1000.

2.6 Tunneled catheters with taurolidine-citrate-heparin lock solution significantly improve the inflammatory profile of hemodialysis patients. N. Fontseré, C. Cardozo, J. Donate, A. Soriano, M. Muros, M. Pons, J. Mensa, J.M. Campistol, J.F. Navarro-González, F. Maduell, Antimicrob Agents Chemother. 2014;58(7):4180-4184.

2.7 Taurolidine-based catheter lock regimen significantly reduces overall costs, infection, and dysfunction rates of tunneled hemodialysis catheters. Winnicki W, Herkner H, Lorenz M, Handisurya A, Kikic Z, Bielesz B, Schairer B, Reiter T, Eskandary F, Sunder-Plassmann G, Sengoelge G. Kidney Int 2018;93(3):753-760.

3. PUBLICATIONS: PROPHYLAXIS OF INFECTION IN ONCOLOGY 3.1 Taurolidine-citrate lock solution (TauroLock) significantly reduces CVAD-associated grampositive infections in pediatric cancer patients.

Simon A, Ammann RA, Wiszniewsky G, Bode U, Fleischhack G, Besuden MM. BMC Infect Dis 2008;8:102.

3.2 Randomized controlled trial of taurolidine citrate versus heparin as catheter lock solution in paediatric patients with haematological malignancies.

Dümichen MJ, Seeger K, Lode HN, Kühl JS, Ebell W, Degenhardt P, Singer M, Geffers C, Querfeld U. J Hosp Infect 2012;80(4):304-309.

3.3 Central venous catheters and catheter locks in children with cancer: a prospective randomized trial of taurolidine versus heparin.

Handrup MM, Møller JK, Schrøder H. Pediatr Blood Cancer 2013;60(8):1292-1298.

4. PUBLICATIONS: PROPHYLAXIS OF INFECTION IN PARENTERAL NUTRITION 4.1 Taurolidine lock solution in the secondary prevention of central venous catheter-associated bloodstream infection in home parenteral nutrition patients.

Touré A, Lauverjat M, Peraldi C, Boncompain-Gerard M, Gelas P, Barnoud D, Chambrier C. Clin Nutr 2012;31(4):567-570.

4.2 Randomised clinical trial: 2% taurolidine versus 0.9% saline locking in patients on home parenteral nutrition. Wouters Y. Theilla M. Singer P. Tribler S. Jeppesen P. B. Pironi L. Vinter-Jensen L. Rasmussen H. H. Rahman F. Wanten G. J. A. Aliment Pharmacol Ther 2018:1-13.

4.3 Taurolidine-citrate-heparin lock reduces catheter-related bloodstream infections in intestinal failure patients dependent on home parenteral support: a randomized, placebo-controlled trial. Tribler S, Brandt CF, Petersen AH, Petersen JH, Fuglsang KA, Staun M, Broebech P, Moser CE, Jeppesen PB. Am J Clin Nutr 2017;106(3):839-848.

5. PUBLICATIONS: MAINTENANCE OF PATENCY BY USE OF UROKINASE CONTAINING LOCK SOLUTIONS 5.1 National Kidney Foundation, KDOQI Guidelines 2000, Guidelines for Vascular Access, guideline 6, Table III-2. Protocols for Urokinase Administration.

KDOQI NKF-. National Kidney Foundation - KDOQI 2000.

5.2 German Guideline for Access Devices in Hemodialysis. Hollenbeck M, Mickley V, Brunkwall J, Daum H, Haage P, Ranft JM, Schindler R, Thon P, Vorwerk D. Der Nephrologe 2009;Volume:158-176.

5.3 Prophylactic urokinase in the management of long-term venous access devices in children: a Children’s Oncology Group study.

Dillon PW, Jones GR, Bagnall-Reeb HA, Buckley JD, Wiener ES, Haase GM, Children’s Oncology G. J Clin Oncol 2004;22(13):2718-2723.

5.4 Safety and efficacy of taurolidine/urokinase versus taurolidine/heparin as a tunneled catheter lock solution in hemodialysis patients: a prospective, randomized, controlled study. Al-Ali F, Hamdy AF, Hamad A, Elsayed M, Iqbal ZZ, Elsayed A, Ibrahim R, Tolba H, Buanan H, Fawzy A. NDT 2017:1-7.

5.5 Taurolidine-based catheter lock regimen significantly reduces overall costs, infection, and dysfunction rates of tunneled hemodialysis catheters. Winnicki W, Herkner H, Lorenz M, Handisurya A, Kikic Z, Bielesz B, Schairer B, Reiter T, Eskandary F, Sunder-Plassmann G, Sengoelge G. Kidney Int 2018;93(3):753-760.

6. PUBLICATIONS: ANTIMICROBIAL ACTIVITY OF TAUROLOCK™ 6.1 In Vitro Approach for Identification of the Most Effective Agents for Antimicrobial Lock Therapy in the Treatment of Intravascular Catheter-Related Infections Caused by Staphylococcus aureus. Hogan S, Zapotoczna M, Stevens NT, Humphreys H, O’Gara JP, O’Neill E. Antimicrob Agents Chemother 2016;60(5):2923-2931.

6.2 Antimicrobial Activity of a Novel Catheter Lock Solution. Shah CB, Mittelman MW, Costerton JW, Parenteau S, Pelak M, Arsenault R, Mermel LA. Antimicrob Agents Chemother 2002;46(6):1674-1679.

6.3 Activities of taurolidine in vitro and in experimental enterococcal endocarditis. Torres-Viera C, Thauvin-Eliopoulos C, Souli M, DeGirolami P, Farris MG, Wennersten CB, Sofia RD, Eliopoulos GM. Antimicrob Agents Chemother 2000;44(6):1720-1724.

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