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

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Summary

Background

A catheter lock solution containing 1.35% taurolidine and 4% citrate could potentially disrupt bacterial surface adherence and consecutive biofilm production due to the anti-adherence properties of taurolidine and the anticlotting and chelator activities of both compounds.

Aim

To compare the impact on microbial catheter colonization and infectious complications of heparin and taurolidine citrate as central venous catheter (CVC) lock solutions in paediatric patients with haematological malignancies.

Methods

Seventy-one patients aged 1.4–18 years were randomized to two treatment groups using either heparin (N = 36) or taurolidine citrate (N = 35). Infectious complications and clinical side-effects were prospectively monitored and microbial colonization of catheters was assessed at the time of removal.

Findings

There were two bloodstream infections in the taurolidine citrate group versus nine in the heparin group (0.3 vs 1.3 infections per 1000 catheter-days; P = 0.03). Fever of unknown origin and catheter occlusions were observed with a similar frequency in both groups. Microbial colonization was found in 25.4% catheters. The time of no-lock use, but not the type of lock solution or time of observation, was a significant predictor of catheter colonization (P = 0.004). Colonization was not observed in CVCs used immediately with taurolidine citrate lock. Seven patients in the taurolidine citrate group (20%) experienced side-effects (nausea, vomiting, abnormal taste sensations).

Conclusion

The use of taurolidine citrate lock solution was associated with a significant reduction in bloodstream infection in immunocompromised paediatric patients. Taurolidine citrate may prevent colonization of CVCs if used from the time of insertion, but not after a period of no-lock catheter use.

Introduction

Central venous access devices constitute a significant risk for infectious complications. Prevention of catheter-related infections is a key measure to improve clinical outcomes, especially in high risk patients. Taurolidine [bis-(1,1-dioxoperhydro-1,2,4-thiadiazinyl-4)methane] is an antimicrobial agent which inhibits and kills a broad range of micro-organisms in vitro including multiresistant strains.1, 2, 3 A catheter lock solution has been developed containing 1.35% taurolidine and 4% citrate. Due to the anti-adherence properties of taurolidine and the anticlotting and chelator activities of both compounds, this lock solution can disrupt bacterial surface adherence and consecutive biofilm production.4, 5

In a previous study in paediatric cancer patients, the use of a taurolidine citrate lock solution resulted in reduction of Gram-positive infections compared with a historic control group of patients treated with a heparin lock solution.6 However, prospective, randomized studies evaluating efficacy and safety of a taurolidine citrate lock solution have not been performed previously in a paediatric population with a high risk for infections. We hypothesized that in such patients, prolonged use of implanted central venous catheters (CVCs) and frequent handling by staff would result in a time-dependent biofilm formation and catheter colonization even in the absence of clinical symptoms. By analysing removed catheters, microbial colonization might serve as an endpoint for evaluating efficacy of catheter lock solutions. We therefore conducted a prospective randomized controlled clinical trial in paediatric patients undergoing chemotherapy for diagnosed malignancy or receiving a stem cell transplantation during 2007–2008; after allocating implanted catheters to a lock solution containing taurolidine citrate or heparin, infectious complications and clinical side-effects were prospectively monitored and microbial colonization of catheters was assessed at the time of removal.

Section snippets

Setting

In the Department of Paediatric Oncology/Haematology of the Charité Medical Center Berlin, each year about 90–100 children/adolescents are newly diagnosed with neoplastic disease and 20–30 with a relapse, and 40 stem cell transplantations are performed. Prior to antineoplastic treatment or stem cell transplantation, all patients receive a tunnelled single, double or triple lumen Broviac/Hickman CVC. Catheters are used immediately after placement for chemotherapy and intravenous

Results

The observation period (duration of catheter use), the locking period (duration of catheter locking) and the days without lock prior to the locking period (no lock use) were similar in both groups of patients (Table II). Seven patients in group 1 (heparin lock) and 8 patients in group 2 (taurolidine citrate lock) were treated in the bone marrow unit and all other patients in the oncology unit, without a significant difference in duration of catheter use or duration of locking (Table II).

Microbiological analysis

Altogether, 51 CVCs were studied for bacterial growth. Seven CVCs (2 in the heparin, 5 in the taurolidine citrate group) were removed for suspected infections, and six of these were without colonization; the other CVCs were removed electively at the end of therapy. Both for the CVCs removed early and for the CVCs removed at the end of therapy, there were no differences between patient groups in observation time, locking time or days without lock during the use of these catheters (Table IV).

Nine

Discussion

In this first prospective randomized trial in paediatric patients undergoing chemotherapy or bone marrow transplantation, the use of taurolidine citrate lock solution was associated with significantly fewer primary BSI. The rate of BSI observed in the heparin lock group (1.3 per 1000 catheter-days) was similar to a previous report in paediatric patients and to the mean rate observed in adults with surgically implanted long term CVCs (1.6 per 1000 catheter-days).7, 9 If calculated for 1000 days

Acknowledgements

We thank all patients and the nurses and physicians of the Department of Paediatric Haematology/Oncology for their support of the study.

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1

Current address: University Medicine Greifswald, Paediatrics and Paediatric Haematology and Oncology, Greifswald, Germany.

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