ANTIMICROBIAL CATHETER LOCK SYSTEM TO PROVIDE PATENCY AND INFECTION CONTROL

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TauroLock™ prevents catheter infections:

ONCOLOGY

Handrup

1,4 0,4

Simon

2,3 0,5

Infections per 1000 catheter daysHeparin TauroLock™

Dümichen

1,3 0,3

PARENTERAL NUTRITION

Tribler

1,0 0,0

Touré

6,58 1,09

Al-Amin

6,3 0,0

Infections per 1000 catheter daysHeparin TauroLock™Saline

DIALYSIS

Infections per 1000 catheter daysHeparin 4% Citrate TauroLock™

Betjes

2,1 0

Allon

5,6 0,5

Winnicki

2,7 0,67

Solomon

3,25 1,22

Murray

1,59 0,69

Fontseré

1,08 0,04

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

TauroLock™ catheter lock solutions were devel­oped for prophylactic use and reduce catheter related infections significantly (~ 90%). The antimicrobial activity of TauroLock™ is based on (cyclo)­taurolidine which is bactericidal, including resistant bacteria such as MRSA and VRE, as well as fungicidal. TauroLock™ does 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 references 1.1).

Prophylaxis against biolog ical occlusion in the catheter:The TauroLock™ Catheter Lock System con­tains a threefold prophylaxis against occlusion in the catheter:

All locking solutions contain citrate as antico­agulant. At the concentration used, 4%, citrate removes calcium safely and effectively from the clotting cascade.

The optional use of low concentrated heparin supports an additional antico agulative effect via binding to antithrombin. The prophylactic use of TauroLock™­ U25.000 (which contains 25.000 IU of urokinase) achieves the most ef­fective prophylaxis against occlusion through its thrombolytic activity.

The decision which locking solution is most adequate depends on the individual patient situation. The alternative use of TauroLock™­Hep500 and TauroLock™­U25.000 may provide an even stronger effect against infection and biofilm formation (Al­Ali et al., 2017; Winnicki et al., 2018).

30% Citrate

10 lo

g cf

u/m

L

Time in days

0 1 2 3 4 24

10 lo

g cf

u/m

L

Time in hours

Legend

*detection limit(10 cfu/ml)

Heparin

10 lo

g cf

u/m

L

0 1 2 3 4 24

Time in hours

10 lo

g cf

u/m

L

0 1 2 3 4 24

Time in hours

46,7% Citrate

10 lo

g cf

u/m

L

Time in days

If used prophylactically, TauroLock™ prevents the de­velopment of a biofilm on the surface of the catheter lumen:

TauroLock™5 months implanted –

No colonization

Heparin Lock – 7 months implanted – S. epidermidis biofilm

covers surface completely

TauroLock™ is bactericidal and fungicidal within 2 hours:

Clearly superior in comparison to the activity of Citrate and Heparin:

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Instillation of TauroLock™

Follow the manufacturer’s instructions that accompany the particular vascular access product utilized. Specific catheter lock volumes are associated with each device.

1. Flush the device with 10 mL of saline.

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

3. Instill TauroLock™ 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. The volume has to be strictly respected. TauroLock™ will remain inside the access device until the next treat­ment (up to a maximum of 30 days).

4. Prior to the next treatment, TauroLock™ must be aspirated (if desired and possible) and discarded in accordance with the institution’s waste policy.

5. Flush the device with 10 mL of saline.

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

No hypocalcaemic effects are observed in contrast to highly concentrated citrate solutions (30% resp. 46,7%) e.g. arrhythmia, cardiac arrest*, emboli**, tingling fingers and metallic taste***.

TauroLock™ is biocompatible and non toxic.

In contrast to highly concentrated citrate there is no protein precipitation if using TauroLock™****.

* Cardiac arrest following injection of concentrated trisodium citrate. Punt CD, Boer WE. Clin Nephrol. 2008 Apr;69(4):317­8

** Embolic complications from central venous hemodialysis catheters used with hypertonic citrate locking s olution. Willicombe MK, Vernon K, Davenport A. Am J Kidney Dis. 2010;55(2):348­51

*** Risks related to catheter locking solutions containing concentrated citrate. Hans­Dietrich Polaschegg, Klaus Sodemann. Nephrol.Dial.Transplant. 2003,18(12):2688­90

**** 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):2953­7

Product selection for application

Dialysis

Oncology

Parenteral Nutrition

Product

Manufacturer:

TauroPharm GmbHAugust­Bebel­Straße 51D­97297 WaldbüttelbrunnTel.: +49 931 304299­0Fax: +49 931 304299­29 ISO 13485

85100/16/18

TauroLock™ catheter lock solutions are available in different containers:

Ampoule (10 x 3 mL)

Ampoule (10 x 5 mL)

Vial (100 x 10 mL)

Vial (5 x 5 mL)

Product

WWW.TAUROLOCK.COM

1. GUIDELINES AND RECOMMENDATIONS

1.1. Guidelines for the Prevention of Intravascular Catheter-related Infections CDC, Center of Disease Control, USA, 20111.2. SF2H Prevention of Infections Associated with Implantable Catheter-Port Systems for Venous Access. 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. 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.

2.4. 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.

2.5. 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.

2.6. 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. Efficacy of taurolidine on the prevention of catheter-related bloodstream infections in patients on home parenteral nutrition. Al-Amin AH, Sarveswaran J, Wood JM, Burke DA, Donnellan CF. J Vasc Access 2013;14(4):379-382.

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.