However, given its poor solubility in water and low bioavailability, it may be less suitable for treating systemic infections 21, 22, 23. Niclosamide (NIC), an anthelmintic drug declared by the WHO as an essential medicine 12, has been identified as one of the most promising candidates to combat Gram-positive infections, especially those caused by S. The release of biocidal agents approach has been extensively investigated over the past years via incorporating or coating medical devices with biocidal compounds such as antibiotics or other active compounds, for instance compounds identified in “repurposing” studies.Īntibacterial drug repurposing entails the use of already approved drugs for novel applications, such as antibacterial indications 11. These can be categorized as: (1) antifouling strategies such as hydration and steric repulsion, specific protein interactions, or low surface energy, and (2) antimicrobial mechanisms such as the release of biocidal agents, or surface microbicidal activity 10. There are many strategies described in the literature to address this increasing problem. Preventing bacterial attachment and subsequent biofilm formation on catheter surfaces would be the most cost-effective strategy to prevent CRBSIs 9. Hence, catheters must be removed and replaced to prevent further medical complications. Bacterial cells encased in biofilm structures are very difficult to be eradicated by the immune defenses and antimicrobial agents 7, 8. CRBSIs are primarily due to bacterial colonization of the catheter surface during insertion leading to a biofilm infection 5. These infections are mainly caused by Gram-positive bacteria, mostly Staphylococcus aureus and Staphylococcus epidermidis 5, 6. Catheter-related bloodstream infections (CRBSIs) increase the morbidity and mortality of intensive care patients with a mortality ranging from 19 to 34% 4.
However, 3.5% of these catheters are colonized by bacterial or fungal pathogens causing serious and costly bloodstream infections 3. At least 150 million intravascular catheters are used annually in North America alone 2. The demand for catheters has increased due to the wide use of such devices in the administration of medications, nutritional support, blood sampling and performing dialysis in critically or chronically ill patients 1. aureus in a biomaterial-associated infection mouse model and has good prospects for preclinical development.Ĭatheters represent an indispensable medical tool to improve the health quality and medical care of patients. In summary, the NIC-releasing hot-melt extruded catheters prevented implant colonization and reduced the bacterial colonization of peri-catheter tissue by methicillin sensitive as well as resistant S. The released NIC from the produced catheters reduced bacterial colonization of the catheter as well as of the surrounding tissue. Moreover, the antibacterial efficacy of NIC-loaded catheters was validated in an in vivo biomaterial-associated infection model using a methicillin-susceptible and methicillin-resistant strain of S. NIC was released in a sustained manner from the catheters and exhibited in vitro antibacterial activity against Staphylococcus aureus and Staphylococcus epidermidis. The mechanical and physicochemical properties of TPU polymers loaded with NIC were studied. Niclosamide (NIC), originally an antiparasitic drug, was incorporated into the polymeric matrix of thermoplastic polyurethane (TPU) via solvent casting, and catheters were fabricated using hot-melt extrusion technology. In this study, we have developed drug-eluting antibacterial catheters to prevent catheter-related infections. Biomaterial-associated infections are a major healthcare challenge as they are responsible for high disease burden in critically ill patients.