Taurolidine – based catheter lock solutions ( TauroLockTM ) - Prescribing Guidance

Publication: 01/06/2009  --
Last review: 08/12/2016  
Next review: 08/12/2019  
Clinical Guideline
CURRENT 
ID: 1796 
Approved By: Improving Antimicrobial Prescribing Group 
Copyright© Leeds Teaching Hospitals NHS Trust 2016  

 

This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
For healthcare professionals in other trusts, please ensure that you consult relevant local and national guidance.

Taurolidine – based catheter lock solutions (TauroLockTM)

This document provides guidance for Microbiologists (including trainees) regarding certain situations in which it would be appropriate to consider the use of taurolidine, in the form of TauroLockTM catheter lock solutions. This document is supplementary to, and should be used in conjunction with, the manufacturer’s instructions for use 1.

The use of taurolidine can be considered within its approved LTHT Drugs and Therapeutics Committee [DTC] applications, other indications will require chairman’s action.

Please follow current LTHT guidelines for management of infected long-term intravascular access devices [detail.aspx?id=1680] 8.

The manufacturer recommends that TauroLockTM should not be used in children under the age of three months due to the risk of adverse effects as a result of the 4% citrate present.

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Introduction

Taurolidine [2 H-1, 2, 4 – thiadiazine -4, 4’ methylenebis (tetrahydro-1, 1, 1’, 1’-tetraoxide)] is a derivative of tauronamide, a naturally occurring aminosulphonic acid, and formaldehyde 2, 3. It has a very broad spectrum of antimicrobial activity 2, 3, 4, 5, 6, 7. This activity is due to the agent’s currently unique cidal mechanism of action, which is believed to be due to the irreversible interaction of its’ methylol derivatives with microbial cell walls 2, 7.
Taurolidine is the active antimicrobial component of TauroLock TM solutions. These products are designed to be instilled into the lumen(s) of vascular access devices. The TauroLock TM product family also include 4% citrate, with or without low concentrations of heparin, to prevent thrombus formation within the catheter. For the purposes of this guidance, it is envisaged that the original TauroLock TM solution (i.e. without additional heparin) would normally be used.

The use of taurolidine in this guidance is in the formulation of these commercially available catheter lock solutions. TauroLock TM solutions are approved for use as “Medical Devices”. Their manufacturer has not attempted to license them as medicines.

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Antimicrobial activity

Taurolidine has been shown to be active in vitro against a very wide range of Gram positive and Gram negative bacteria, as well as non tuberculous mycobacteria and certain fungi 3, 4, 6, 7. It is bactericidal at concentrations ranging between 250 and 2000 mg/L 3, 4, 7. Bacteria shown to be susceptible include obligate aerobes as well as facultative and obligate anaerobic organisms. Currently, the acquisition or development of in vitro resistance has not been demonstrated 1, 3, 7. The susceptibility testing of individual clinical isolates in vitro has been arranged with / by the manufacturer to date 4, however a local testing capacity will be developed as clinically required.


Taurolidine has in vitro activity against 7
Gram positive bacteria, including
Staphylococcus aureus [meticillin resistant and meticillin susceptible strains]
Coagulase negative staphylococci
Streptococci [including β-haemolytic streptococci, Streptococcus pneumoniae, oral streptococci]
Enterococci [including vancomycin resistant isolates]
bacilli such as Corynebacterium jeikeium and Lactobacillus spp

Gram negative bacteria, including
Enterobacteriaceae [including Escherichia coli, Klebsiella pneumoniae, Enterobacter species, Citrobacter freundii ]
Acinetobacter spp
Pseudomonas aeruginosa
Stenotrophomonas maltophilia

Non tuberculous mycobacteria, including 4
Mycobacterium. fortuitum
Mycobacterium chelonae
Mycobacterium avium complex,
Mycobacterium terrae

Fungi, including
Candida albicans
Aspergillus niger.


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Dose/Routes of administration

TauroLock TM is indicated for patients using a tunnelled silicone or polyurethane catheter – based device for their vascular access 1. It is normally supplied in 5 ml ampoules, intended for single use. The TauroLock TM solution should be instilled into the catheter lumen(s). The volume of solution required depends on the particular vascular access device being used and its specific fill volume. The catheter lock solution has been shown to be stable for well over 7 days at 37°C, with a recommended minimum dwell time of two hours for prevention of luminal catheter colonisation. The optimal dwell time for treating established line colonisation or associated infection is not known. The luminal solution should be withdrawn prior to the use of the catheter for any other purpose.

Paediatric patients:
It is recommended that TauroLock TM should not be used in patients under the age of three months due to small volume of distribution of the citrate.

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Pharmacokinetics.

Absorption: Not applicable - taurolidine in the form of TauroLockTM catheter lock solutions are designed for catheter instillation only. It must be given by intra-device instillation; there is no oral preparation available.

Distribution:TauroLock TM solution is designed for intra-vascular catheter instillation only.

Excretion/metabolism: It is recommended by the manufacturer that TauroLock TM solutions are withdrawn from the catheter prior to the catheter’s use for any other purpose. If the solution cannot be withdrawn and / or is injected into the patient, then taurolidine rapidly breaks down in the plasma into the naturally occurring amino acid taurine, carbon dioxide and water.

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Side effects

There are no known adverse effects of taurolidine if the catheter lock solution is injected into the patient rather than being withdrawn. It is metabolised rapidly into the natural amino acid taurine, carbon dioxide and water.

The concentration of 4% citrate is safe and effective for preventing thrombus formation, according to the FDA1. Higher concentrations of citrate can be associated with adverse effects due to hypocalcaemia, such as metallic taste, parasthesiae, even arrhythmias or cardiac arrest.

It is recommended that TauroLock TM should not be used in patients under the age of three months due to small volume of distribution of the citrate.

TauroLock TM may cause stinging if injected into the subcutaneous or intramuscular space.

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Prophylaxis

TauroLock TM solutions have been developed primarily for the prevention of infections of long-term intra-vascular catheter infections 1, 8, 9. This guidance is for the management of infected long-term intra-vascular catheters 8, 9 and does not address primary prophylaxis.

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Treatment

Taurolidine in the form of a TauroLockTM solution may be considered alone or as an adjunct to appropriate systemic antimicrobial therapy, for the treatment of colonised or infected long-term intra-vascular catheter where luminal involvement has been confirmed by paired through –line and peripheral Blood Cultures (see LTHT Antimicrobial Guidance for the Management of infected long-term intra-vascular catheters) 8,9.

The recommended dose is the appropriate fill volume for the lumen(s) of the affected catheter. This should normally be instilled for a minimum dwell time of twenty – four hours and a maximum dwell time of seven days prior to solution change. If the catheter has more than one lumen, it is normally appropriate to instil the solution into all the lumens when not in use. If the catheter is still required for other uses at the same time, it is usually appropriate to alternate the lumen(s) being locked with the solution, rotating 24 hourly. The lumens should normally be locked for 7 – 14 days in total 8, 9 or as long as systemic therapy is being administered if longer (e.g. for a catheter infection due to a rapid growing mycobacteria). It may be appropriate to continue locking the catheter with TauroLockTM solution instead of the normal flush solution used, after the treatment course has been completed with the aim of preventing subsequent line infection(s) (“secondary prophylaxis”). This approach should be considered if alternative access sites are very limited or non-existent; if the patient has had recurrent long-term catheter infections; or catheter change remains contra-indicated (e.g. due to coagulopathy) 1.

For TauroLockTM to be suitable for use, two questions should be answered.

1. Is it appropriate to attempt to salvage this catheter 8,9?

  1. The catheter should be designed for long-term use (e.g. Hickman, Groschong or Tesio lines), and such intra-vascular access is still medically required.
  2. The infection is uncomplicated 8, 9 – i.e. no concurrent clinical evidence of severe sepsis; no evidence of tunnel infection; septic thrombosis; nor endocarditis, osteomyelitis, nor other metastatic infection.
    The specific location of any infection is important regarding the decision to attempt salvage with line lock therapy. Such therapy, including using TauroLock TM will only be potentially active against organisms situated within the lumen of the catheter. If the infection is demonstrably entirely extra-luminal, locks are not appropriate except in rare cases for secondary prophylaxis (see below).
  3. The causative pathogen is not S. aureus, P. aeruginosa or fungus (usually Candida sp.) 8, 9. Lines should normally be removed for certain other pathogens, such as rapid growing mycobacteria or Bacillus species 4, 8, 9.

2. Is taurolidine the most appropriate antimicrobial agent for the lock solution?

Currently in LTHT, the two other widely available antimicrobials in lock solutions are vancomycin or gentamicin. TauroLockTM solution is likely to be suitable if;

  1. The organism is resistant (intrinsic or acquired) to the two other agents. Certain organisms are not treated effectively in vivo even if they appear sensitive in vitro to one (or both) of these antibiotics, e.g. rapid growing mycobacteria or S. maltophilia.
  2. There is a poly-microbial infection of both Gram negative and Gram positive organisms.
  3. The patient is allergic to other suitable antimicrobial lock solution(s).
  4. Vancomycin and / or gentamicin lock solutions have been tried and have failed on microbiological or clinical grounds, but line salvage is still necessary and appropriate.

If peripheral Blood Cultures are positive with the same causative pathogen despite ≥ 72 hours of suitable antimicrobial therapy, then the infected long-term catheter should usually be removed 8, 9.

Luminal Blood Cultures should be requested to be taken on cessation of taurolidine lock treatment to demonstrate microbiological clearance of the luminal infection or colonisation (preferably at least 2-3 days post cessation) 8, 9.

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Prescribing restriction

Taurolidine / TauroLockTM is a partially restricted antimicrobial; a restricted antimicrobial code from microbiology and restricted antimicrobial request form will be required only for use outside LTHT guidelines.

Provenance

Record: 1796
Objective:
Clinical condition:
Target patient group: All patients > 3months old
Target professional group(s): Secondary Care Doctors
Pharmacists
Allied Health Professionals
Adapted from:

Evidence base

References

  1. TauroLock product information, instructions for use. TauroPharm GmbH.
  2. Koldehoff, M, and J. L. Zakrzewski. Taurolidine is effective in the treatment of central venous catheter – related bloodstream infections in cancer patients. Int J Antimicrob Agents:2004;24:491 – 495.
  3. Shah, C.B., M. W. Mittleman, J. W. Costeron, S. Parenteau, M. Palak, R. Arsenault, and L. A. Mermel. Antimicrobial activity of a novel catheter lock solution. Antimicrob Agents and Chemother;2002; 46:1674–1679.
  4. Collyns, T. A., A. Young, C. Weis, G. Robinson, M. Hufton, S. Roberts, and J. D. Chester. First report world-wide of clinical use of taurolidine – 4% citrate catheter lock solution to tackle an intravascular catheter colonised with a mycobacteria; with a very successful outcome. Abstracts of 47th Interscience Conference on Antimicrobial Agents and Chemotherapy, 2007, American Society for Microbiology, abstr K-1738.
  5. Mermel L., and S. Parenteau. Efficacy of the Biolink Catheter Lock Solution (CLS TM) for Dialock ® haemodialysis access port and catheters – an in vitro model. Abstracts of the International Conference on Nosocomial and Healthcare associated Infections. 2000, Centers for Disease Control, Atlanta, Ga.
  6. Sheretz, R.J., M. S. Boger, C. A. Collins, L. Mason and I. I. Raad. 2006. Comparative in vitro efficacies of various catheter lock solutions. J Clin Microbiol. 2006; 50;1865 – 1868.
  7. Torres-Viera, C., C. Thauvin – Eliopoulos, M. Souli, P. DeGirolami, M. G. Farris, C. B. Wennersten, R. D. Sofia, and G. M. Eliopoulos. J Clin Microbiol 2000;1720 – 1724.
  8. Sandoe J, A Olusoga, T A Collyns, M Wright, G Cook. Guideline for management of infected long-term intravascular access devices in adults. Leeds Health Pathway 2009 detail.aspx?id=1680
  9. Mermel L. A., M. Allon, E. Bouza, D. E. Craven, P. Flynn, N. P. O’Grady, I. I. Raad, B. J. A. Rijnders, R. J. Sheretz, and D. K. Warren. Clinical Practice Guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 Update by the Infectious Diseases Society of America. Clin Infect Dis 2009; 49:1-45.

Approved By

Improving Antimicrobial Prescribing Group

Document history

LHP version 1.0

Related information

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