According to the National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (KDOQI) clinical practice guideline for vascular access, there is inadequate evidence to make a recommendation on the comparative use of the following central venous catheter (CVC) locking agents for CVC dysfunction or infection prophylaxis: tinzaparin versus unfractionated heparin, taurolidine/citrate versus heparin with or without gentamicin, neutral valve connector (Tego [ICU Medical]) versus citrate (46.7%) locking solution. It is recommended that larger multicenter randomized controlled trials are needed to evaluate citrate and taurolidine. [1]
A 2020 meta-analysis investigated the efficacy and safety of antimicrobial lock solutions for prevention of central-line-associated bloodstream infection (CLABSI). A total of 49 randomized controlled trials (N= 7,020 patients) were included for analysis. Patients were ages 18 years or older, on dialysis, and trials reported either primary (catheter-related bloodstream infection [CRBSI] and bleeding rates) or secondary (catheter malfunction, exit-site infection, and all-cause mortality) parameters. Subgroup analysis demonstrated that seven antibiotics (cloxacillin, cefotaxime, linezolid, vancomycin, gentamicin, minocycline, and taurolidine) were effective for prevention of CRBSI. However, the lack of head-to-head trials prevents hierarchical classification of antibiotics. Data for taurolidine was mainly based on 4 studies of taurolidine/citrate or taurolidine/urokinase, with only one involving use of taurolidine/heparin as the control group. Pairwise meta-analysis for taurolidine reports a risk ratio (RR) of 0.29 (95% confidence interval [CI] 0.03 to 2.50) and network meta-analysis reports a RR of 0.32 (95% CI 0.19 to 0.56). [2]
A 2021 systematic review and meta-analysis investigated the efficacy of antibiotic and antimicrobial lock solutions for prevention of hemodialysis CRBSI. A total of 26 studies were included, encompassing a total of 4,967 patients. Antibiotic interventions (n= 889 patients) included gentamicin (most common), as well as minocycline, vancomycin, trimethoprim, and cefotaxime. A proportion of patients were also treated with various non-antibiotic antimicrobial solutions (n= 1,662). Four studies compared 1.35% taurolidine and 4% sodium citrate vs. heparin. All included studies reported incidence of catheter-related bacteremia (CRB), with an overall pooled RR showing intervention was associated with a 30% lower incidence of CRB compared to heparin (RR 0.30; 95% CI 0.25 to 0.36; p<0.001). When evaluating subgroups, administration of antibiotics specifically resulted in a 28% decrease in CRB episodes compared to heparin (RR 0.28; 95% CI 0.21 to 0.37; p<0.0001). Conversely, administration of antimicrobial solutions was associated with 32% reduced risk of CRB compared to patients in the heparin control group (RR 0.32; 95% CI 0.25 to 0.41; p<0.0001). Neither of these two interventions was favored over the other, as both were determined to be effective in reducing CRBSI. [3]
A 2022 systematic review and meta-analysis evaluates the efficacy of taurolidine in antibiotic lock solutions for patients with CVC-related bloodstream infections. Fourteen randomized controlled trials with a total of 1,219 patients were included that assessed taurolidine lock solutions with or without heparin and/or citrate versus regular saline or heparin locks; one study used citrate locks as a comparator. Findings were reported as a pooled incidence rate ratio (IRR), comprising incidence rates (IR) of CVC-related bloodstream infections per 1,000 CVC-days. Overall, taurolidine lock solutions were favored, with a pooled IRR of 0.30 (95% CI 0.19 to 0.46; 9 studies; 918 patients). Adverse events, reported in ten studies, were mild and limited in incidence. Although taurolidine lock solutions appear to be a promising avenue for prophylaxis, quality of evidence is low with a high risk of bias, and more robust studies should be undertaken to provide firm conclusions on its efficacy. [4]
A dated 2014 meta-analysis also studied the use of antimicrobial lock solutions to prevent CLABSIs, based on data from 23 randomized studies (n= 2,896 patients). Most of the sample consisted of adult hemodialysis patients. Antimicrobial lock solutions utilized included taurolidine (1 study), taurolidine/citrate (2 studies), and taurolidine/citrate with heparin (1 study), as well as ethanol and heparin, gentamicin citrate, vancomycin and heparin, linezolid and heparin, and others. When comparing use of all antimicrobial lock solutions, a 69% reduction in CLABSI rate was reported (RR 0.31; 95% CI 0.24 to 0.40) compared to heparin. No significant increase in catheter failure was reported due to non-infectious complications. All-cause mortality was comparable between groups. For taurolidine specifically, a subgroup analysis indicated a RR of 0.24 (95% CI 0.12 to 0.46) compared to heparin; however, the formulation of taurolidine used may not have been the specific combination utilized in Defencath. Overall, results indicated use of antimicrobial lock solutions are effective for prevention of CVC infections. The authors discussed that utilization of antimicrobial lock therapy may be of limited utility in critically ill and oncology patients with catheters in continuous use while being more beneficial for patients with long-term catheters. Evidence determining optimal dwell time and concentration for various lock solutions is still lacking. [5]