Is there any safety or efficacy data to support the use of taurolidine locks in pediatric patients with central line infections?

Comment by InpharmD Researcher

Available data suggest that taurolidine lock solutions may reduce the risk of catheter-related bloodstream infections (CRBSIs) in pediatric patients with central venous access. Across multiple analyses, taurolidine, often combined with citrate or heparin, was associated with significantly lower infection rates than heparin alone and ranked among the most effective options for CRBSIs prevention. While no major safety concerns have emerged, findings are largely based on small studies with methodological limitations, highlighting the need for more robust trials.

Background

A 2024 network meta-analysis (NMA) evaluated the comparative efficacy of central venous access device (CVAD) lock solutions used in pediatric patients for the prevention and treatment of catheter-associated complications, including bloodstream infection (BSI), thrombosis, and catheter occlusion. The analysis included 29 randomized controlled trials (RCTs), encompassing 2,970 pediatric patients and 3,053 CVADs, spanning publications from 1990 to 2022. CVAD types varied and included tunneled-cuffed catheters, totally implanted devices, peripherally inserted central catheters, and umbilical venous catheters. Lock solutions were categorized into seven types: heparin, saline, ethanol, chelating agents (e.g., taurolidine-citrate, minocycline-edetic acid), antibiotics (e.g., vancomycin, amikacin), thrombolytics (e.g., urokinase, tissue plasminogen activator), and other (e.g., ascorbic acid). Solutions were analyzed based on their primary or secondary use in either prevention or treatment. The meta-analysis found that chelating and antibiotic lock solutions demonstrated significantly lower odds for CVAD-associated BSI prevention compared to heparinized saline, with odds ratios (ORs) of 0.11 (95% confidence interval [CI]: 0.02–0.67; moderate-quality evidence; 4 trials specific to taurolidine-citrate) and 0.19 (95% CI: 0.05–0.79; high-quality evidence), respectively. Notably, post hoc subgroup analyses conducted for CVAD-BSI (prevention), assessing only taurolidine in the chelating agent group, yielded similar OR to the primary analysis (OR 0.12; 95% CI: 0.01–1.57). Thrombolytic agents were associated with a reduced risk of catheter occlusion (OR: 0.64; 95% CI: 0.44–0.93; low-quality evidence), while ethanol was linked with increased risk (OR: 2.84; 95% CI: 1.31–6.16; high-quality evidence). No conclusive benefits were observed with any lock solution for prevention or treatment of CVAD-associated thrombosis, treatment of CVAD-associated BSI, CVAD failure, or mortality. Overall, the authors reported wide confidence intervals and low certainty of evidence for many comparisons, emphasizing the need for further high-quality, adequately powered investigations to guide optimal lock solution selection in pediatric practice. [1]

Another NMA, published in 2021, evaluated the effectiveness of various catheter lock solutions (CLSs) for preventing catheter-related bloodstream infections (CRBSIs) in pediatric patients with central venous catheters. The analysis included 13 RCTs with a total of 1,335 patients and used a random-effects model to estimate risk ratios. Taurolidine plus heparin was found to be significantly more effective than heparin alone in reducing CRBSI risk (risk ratio [RR] 0.21; 95% CI 0.09 to 0.51), while no significant differences were observed between heparin and other CLSs such as vancomycin, ethanol, fusidic acid, amikacin, or their combinations. Based on the surface under the cumulative ranking curve, taurolidine plus heparin (85.3%) ranked highest for CRBSI prevention, followed by fusidic acid plus heparin (77.0%) and amikacin plus heparin (65.7%). The analysis found no significant global inconsistency among the included studies. Based on these findings, it was concluded that taurolidine appeared to be the most effective CLS for preventing CRBSIs in pediatric patients, though additional well-designed randomized trials are needed to confirm these findings. [2]

A 2020 meta-analysis synthesized data from four RCTs evaluating the efficacy of taurolidine lock solution in preventing CRBSIs among pediatric patients with central venous catheters (CVCs). The trials, conducted across tertiary care centers in European countries, enrolled a total of 476 children under 19, with individual study sample sizes ranging from 35 to 90 participants per group. The included populations primarily consisted of pediatric oncology patients and postsurgical patients requiring long-term central access for nutrition or medication. Across all four RCTs, taurolidine was administered as a 1.35% solution combined with 4% sodium citrate, while comparator arms utilized either heparin or no lock solution. The pooled analysis demonstrated a statistically significant 77% relative risk reduction in the total number of CRBSIs in patients treated with taurolidine compared to controls (RR 0.23; 95% CI 0.13 to 0.40; I²= 0%; p<0.00001). Additionally, the incidence rate of CRBSIs, defined as infections per 1000 catheter-days, was notably reduced in the taurolidine group, with a mean difference of -1.12 (95% CI -1.54 to -0.71; I²= 1%; p<0.00001) across three contributing studies. However, no significant difference was observed in the number of catheters removed due to infection or suspected infection (RR 0.68; 95% CI 0.22 to 2.10; I²= 56%; p= 0.50), likely attributable to heterogeneity in catheter removal criteria and the limited event rate. Notably, methodological quality was limited as stated by the authors; none of the studies were blinded, and only one employed adequate random sequence generation. Despite these limitations, the authors concluded that taurolidine may reduce CRBSI rates in pediatric patients. Still, they emphasized the need for further investigation through larger, rigorously designed trials to confirm these findings. [3]

References:

[1] Takashima M, Ezure Y, Furuya-Kanamori L, et al. Pediatric Central Venous Access Device Lock Solutions: A Network Meta-analysis. Pediatrics. 2024;153(2):e2023063264. doi:10.1542/peds.2023-063264
[2] Guo Q, Lv Z, Wang H, et al. Catheter lock solutions for reducing catheter-related bloodstream infections in paediatric patients: a network meta-analysis. J Hosp Infect. 2021;118:40-47. doi:10.1016/j.jhin.2021.09.013
[3] Sun Y, Wan G, Liang L. Taurolidine lock solution for catheter-related bloodstream infections in pediatric patients: A meta-analysis. PLoS One. 2020;15(4):e0231110. Published 2020 Apr 7. doi:10.1371/journal.pone.0231110

Literature Review

A search of the published medical literature revealed 2 studies investigating the researchable question:

Is there any safety or efficacy data to support the use of taurolidine locks in pediatric patients with central line infections?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→



Please see Tables 1-2 for your response.


 

The Effectiveness of Taurolidine Antimicrobial Locks in Preventing Catheter-Related Bloodstream Infections (CRBSIs) in Children Receiving Parenteral Nutrition: A Case Series
Design

Retrospective case series study

N= 14

Objective To assess the efficacy of taurolidine lock (TL) in preventing catheter-related bloodstream infections (CRBSIs) and related hospitalizations in children with parenteral nutrition (PN) in the home setting
Study Groups All patients (n= 14)
Inclusion Criteria Children with intestinal failure, treated with PN via a central line after 2017, and administered TL
Exclusion Criteria Not specified
Methods Patients received TauroLock™ (1.35% taurolidine + 4% citrate) daily after parenteral nutrition. The treatment involved flushing the device with saline, instilling TauroLock™ slowly, and keeping it in the device until the next treatment. Data on CRBSI episodes and hospitalizations were collected from medical files. 
Duration January 2017 to June 2024
Outcome Measures Rate of CRBSI episodes per 1000 days, rate of hospitalization episodes per 1000 days, pathogen distribution
Baseline Characteristics Characteristic All patients (n= 14)
Ethnicity - Bedouin 12 (86%)
Male 10 (71%)
Mean age at TL administration, years 7.3 ± 4.8

Background illnesses

Short bowel syndrome

Tufting enteropathy

Neurogenin 3 deficiency

Jejunal atresia

HRD

 

7 (50%)

3 (21%)

2 (14%)

1 (7%)

1 (7%)

Results Endpoint Pre-TL (n= 11,850 days) Post-TL (n= 15,150 days) p-value
CRBSI episodes per 1000 days 6.2 3.7 0.0008
Hospitalization episodes per 1000 days 7.6 4.5 0.001
Gram-negative bacteria CRBSI episodes per 1000 days 6.1 3.2 0.0008
Gram-positive bacteria CRBSI episodes per 1000 days 6 3.4 0.003
Fungal CRBSI episodes per 1000 days 0.6 0.4 0.66
Adverse Events Not specified
Study Author Conclusions Taurolidine lock treatment for children with central-line PN resulted in a substantial decrease in CRBSI episodes and related hospitalizations.
InpharmD Researcher Critique The study provides strong evidence for the effectiveness of taurolidine locks in reducing CRBSI episodes and hospitalizations in children with intestinal failure. However, the single-center, retrospective design and small sample size may limit the generalizability of the findings. Additionally, the study did not compare TL with other controls, such as heparin alone, which could have provided more comprehensive insights into its relative efficacy. 
References:

Ling G, Ben-Shimol S, Elamour S, et al. The Effectiveness of Taurolidine Antimicrobial Locks in Preventing Catheter-Related Bloodstream Infections (CRBSIs) in Children Receiving Parenteral Nutrition: A Case Series. Antibiotics (Basel). 2024;13(9):847. Published 2024 Sep 5. doi:10.3390/antibiotics13090847

 

Use of 2% taurolidine lock solution for treatment and prevention of catheter-related bloodstream infections in neonates: a feasibility study

Design

Retrospective study

N= 37

Objective

To assess the feasibility and outcomes of using taurolidine lock therapy both prophylactically and therapeutically for the prevention and treatment of catheter-related bloodstream infections (CRBSIs) in term and preterm neonates

Study Groups

Therapeutic taurolidine (n= 21)

Prophylactic taurolidine (n= 16)

Inclusion Criteria

Newborns hospitalized in the neonatal intensive care unit (NICU); with centrally inserted central catheters (CICCs); received taurolidine either prophylactically or as treatment for a CRBSI diagnosed using delayed time to positivity

Exclusion Criteria

Newborns with epicutaneo-caval catheters (ECCs)

Methods

Patients were retrospectively identified from two level-III NICUs in Italy and Belgium, where they had received taurolidine either prophylactically or therapeutically for CRBSI. Group 1 included neonates with confirmed CRBSI who received therapeutic taurolidine locks (TTL) in addition to intravenous antibiotics, with taurolidine instilled for at least 120 minutes every 24 hours until infection resolution, while Group 2 included neonates at high risk of CRBSI who received prophylactic taurolidine locks (PTL) for at least 30 minutes every 48 hours until catheter removal. Data on catheter duration, infection-related outcomes, and taurolidine-related adverse events were collected from medical records, and all parents had provided consent for use of clinical data.

Duration

Between January 1, 2019, and December 31, 2022

Outcome Measures

Effectiveness of taurolidine lock in preventing and treating CRBSI

Baseline Characteristics

 

All patients (N= 37)

Gestational age, weeks (IQR)

Born with a gestational age <35 weeks

32 (23-40) 

24 (65%)

Born preterm

18 (48.6%)

Duration of vascular catheterization, days (IQR)*

23 (7-105)

Types of infections (n= 16)**

Prematurity

Congenital heart disease

Short bowel syndrome

Congenital diaphragmatic hernia

Oesophageal atresia

 

11 (69%)

3 (19%)

6 (38%)

1 (6.3%)

1 (6.3%)

Abbreviation: IQR= interquartile range 

*Total of 42 central venous catheters (CVCs) were evaluated 

**Characteristics of neonatal diseases in the prophylactic group

Among the 37 neonates, 31 (81%) were treated for a surgical disease, with short bowel syndrome and cardiac diseases being the most frequent surgical issues.

Results

Endpoint

All patients 

Achieved clinical symptom disappearance and bacteraemia clearance with therapeutic taurolidine (n= 21)

18 (85.7%)

In the prophylactic taurolidine group (n= 16), no CRBSI was observed during the duration of the catheter placement. 

Adverse Events

No cases of mechanical CVC malfunctioning were recorded, and taurolidine lock was well tolerated in all infants. No cases
of altered liver or renal function, heart rate and/or blood pressure, or alteration of neurological status were documented.

Study Author Conclusions

In this retrospective study, taurolidine was successfully used in neonates both for prevention and treatment of CRBSI, without major undesired effects. A larger cohort and a randomized clinical trial is warranted in order to establish its efficacy and safety in neonates.

InpharmD Researcher Critique

The retrospective nature of the study design has its inherent limitations. Additionally, the findings may not be generalizable to broader pediatric populations due to the specific focus on neonates.



References:

Savarese I, Yazami S, De Rose DU, et al. Use of 2% taurolidine lock solution for treatment and prevention of catheter-related bloodstream infections in neonates: a feasibility study. J Hosp Infect. 2024;143:76-81. doi:10.1016/j.jhin.2023.11.003