DefenCath™ is a proprietary formulation of taurolidine and heparin with broad antimicrobial activity that is currently being investigated for use as a catheter lock solution, with the aim of reducing the risk of catheter-related bloodstream infections (CRBSIs) from central venous catheters (CVCs). DefenCath™ is an investigational product in the US and is being investigated in patients undergoing hemodialysis with central venous catheters. The U.S. Food and Drug Administration (FDA) has granted DefenCath™ both Fast Track and Qualified Infectious Disease Product designations.
Taurolidine, the key antimicrobial compound in DefenCath™, is a derivative of the naturally occurring amino acid, taurine, with in-vitro studies indicating broad antimicrobial activity against gram-positive and gram-negative bacteria, including antibiotic resistant strains, as well as mycobacteria and clinically relevant fungi including Aspergillus.
Taurolidine's mechanism of action is the irreversible binding of its methylol groups to microbial cell walls and subsequent loss of cell wall integrity leading to cell death. Taurolidine also reduces bacterial adhesion to mammalian cells, as shown with E. coli and bladder epihelium. Taurolidine also neutralizes bacterial exotoxins and endotoxins.
Heparin is a well-known anticoagulant that is widely used in hemodialysis.
CRBSIs are characterized by the presence of bacteremia originating from a central venous catheter. CRBSIs are one of the most frequent, deadly, and expensive complications of CVCs and possibly the most well-known reason for nosocomial bacteremia.
While CVCs comprise only ~20% of vascular-access types among the prevalent hemodialysis patients, they account for ~70% of CRBSIs.
Patients with a CVC for vascular access have a 7-11-fold higher risk for CRBSIs when compared to other types of vascular access. Additionally, CRBSIs are associated with increased risk for morbidity and mortality and are the most common cause of nosocomial bacteremia. The risk of CRBSIs increases linearly with the duration of catheter use. One large observational study estimates the cumulative risk of CRBSIs to be 54% at six months and 79% at 12 months post first-ever tunneled dialysis catheter placement
CRBSI is described as the presence of bacteremia originating from infections caused by bacterial or fungal pathogens from an intravenous catheter. Bacterial or fungal colonization of the extraluminal areas or an intraluminal contamination of the catheter via exit site (skin) migration of the microorganisms along the extraluminal catheter surface to the bloodstream may result in CRBSIs.
Source: NHSN Dialysis Event Surveillance
39.5% of Staphylococcus aureus were methicillin resistant
Other important drug-resistant pathogens included:
*Isolated pathogens from all BSIs (n=32,016).
Among all BSIs reported (N=29,516), 76.5% (n=22,576) were access related.
63.0% of BSIs and 69.8% of access-related BSIs occurred in patients with a CVC.1
A major source of infection is the contamination of the intravenous catheters that comes from the patient’s skin and the hands of medical personnel who handle the catheters during the process of accessing the veins. However, many other interrelated factors have been identified in the pathogenesis of CRBSI such as host or patient-related factors, pathogen-related factors, HD procedure-related factors, and catheter-related factors.
CRBSIs increasingly becoming nosocomial and polymicrobial due to the congregate setting of hemodialysis clinics and shared caregivers.
1. Nguyen DB, et al. Clin J Am Soc Nephrol. 2017;12(7):1139–1146. 2. Merck Manuals Professional Version. Overview of Bacteria. https://www.merckmanuals.com/professional/infectious-diseases/bacteria-and-antibacterial-drugs/overview-of-bacteria. Accessed October 14, 2020. 3. Shanson, D.C. Classification and pathogenicity of microbes. 2nd ed. In: Shanson, D.C., Microbiology in Clinical Practice. Elsevier; 1989:3–31. 4. Johns Hopkins ABX Guide. Acinetobacter baumannii. https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_ABX_Guide/540003/all/Acinetobacter_baumannii. Accessed October 14, 2020. 5. Johns Hopkins ABX Guide. Stenotrophomonas maltophilia. https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_ABX_Guide/540520/all/Stenotrophomonas_maltophilia. Accessed October 14, 2020. 6. Johns Hopkins ABX Guide. Candida species. https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_ABX_Guide/540076/all/Candida_species. Accessed October 14, 2020. 7. Johns Hopkins ABX Guide. Burkholderia cepacia complex. https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_ABX_Guide/540069/all/Burkholderia_cepacia_complex. Accessed October 14, 2020.
