Randomized controlled trial of taurolidine citrate versus heparin as catheter lock solution in paediatric patients with haematological malignancies
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.
References (12)
- et al.
The risk of bloodstream infection in adults with different intravascular devices: a systematic review of 200 published prospective studies
Mayo Clin Proc
(2006) - et al.
Activities of taurolidine in vitro and in experimental enterococcal endocarditis
Antimicrob Agents Chemother
(2000) - et al.
Antimicrobial activity of a novel catheter lock solution
Antimicrob Agents Chemother
(2002) - et al.
Taurolidine: in vitro activity against multiple-antibiotic-resistant, nosocomially significant clinical isolates of Staphylococcus aureus, Enterococcus faecium, and diverse Enterobacteriaceae
Chemotherapy
(1993) - et al.
A comparative study of the microbial antiadherence capacities of three antimicrobial agents
J Clin Pharm Ther
(1987) - et al.
The role of chelators in preventing biofilm formation and catheter-related bloodstream infections
Curr Opin Infect Dis
(2008)
Cited by (61)
Catheter lock solutions for reducing catheter-related bloodstream infections in paediatric patients: a network meta-analysis
2021, Journal of Hospital InfectionCitation Excerpt :All studies were heparin-controlled trials. Eight studies included oncology patients [10–12,20,21,24,25,27]. Of the study population, 270 (20.2%) were neonates [23,26,28].
Validity of surrogate endpoints assessing central venous catheter-related infection: evidence from individual- and study-level analyses
2020, Clinical Microbiology and InfectionComparative efficacy of various antimicrobial lock solutions for preventing catheter-related bloodstream infections: A network meta-analysis of 9099 patients from 52 randomized controlled trials
2019, International Journal of Infectious DiseasesCitation Excerpt :It was shown that citrate lock with non-tunneled catheters was more effective in preventing exit-site infection than heparin (risk ratio (RR) 0.48, 95% CI 0.31–0.75), while the risk of exit-site infection was similar for citrate and heparin with tunneled catheters (RR 0.97, 95% CI 0.62–1.51). A limitation of this study is that seven of the studies included (Raad et al., 2016; Moghaddas et al., 2015; Dümichen et al., 2012; Boersma et al., 2015; Souweine et al., 2015; Goossens et al., 2013; Wouters et al., 2018) were deemed to have a high overall risk of bias (13.5%). In three of these (Raad et al., 2016; Dümichen et al., 2012; Souweine et al., 2015), this was due to the high risk of bias resulting from the failure to blind participants or outcome assessment, and in another three (Boersma et al., 2015; Goossens et al., 2013; Wouters et al., 2018), it was due to the attrition rate, which was greater than 5% of the total sample size.
Incidence, severity and outcome of central line related complications in pediatric oncology patients; A single center study
2019, Journal of Pediatric SurgeryCitation Excerpt :Unfortunately, a great deal of the CLABSI episodes will still result in removal of the CVAD owing to continuing symptoms, relapses or reinfections. In the prevention of CLABSIs, the use of lock solutions containing taurolidine, ethanol or citrate appears to be promising; however, further research on this subject is needed and strongly recommended [11,29,32–35]. Patients diagnosed with hematooncologic malignancies were more at risk for CVAD-related complications in general; this might be because of more frequent CVAD-manipulation in this patient group [1,7,9].
- 1
Current address: University Medicine Greifswald, Paediatrics and Paediatric Haematology and Oncology, Greifswald, Germany.