S-Nitroso-N-acetyl-l-cysteine Ethyl Ester (SNACET) Catheter Lock Solution to Reduce Catheter-Associated Infections

Abstract

Antimicrobial-lock therapy is an economically viable strategy to prevent/reduce the catheter-related bloodstream infections (CRBSI) that are associated with central venous catheters (CVCs). Herein, we report the synthesis and characterization of the S-nitroso-N-acetyl-l-cysteine ethyl ester (SNACET), a nitric oxide (NO)-releasing molecule, and for the first time its application as a catheter lock solution to combat issues of bacterial infection associated with indwelling catheters. Nitric oxide is an endogenous gasotransmitter that exhibits a wide range of biological properties, including broad-spectrum antimicrobial activity. The storage stability of the SNACET and the NO release behavior of the prepared lock solution were analyzed. SNACET lock solutions with varying concentrations exhibited tuneable NO release at physiological levels for >18 h, as measured using chemiluminescence. The SNACET lock solutions were examined for their efficacy in reducing microbial adhesion after 18 h of exposure toStaphylococcus aureus (Gram-positive bacteria) andEscherichia coli (Gram-negative bacteria). SNACET lock solutions with 50 and 75 mM concentrations were found to reduce >99% (ca. 3-log) of the adhered S. aureus and E. coli adhesion to the catheter surface after 18 h. The SNACET lock solutions were evaluated in a more challenging in vitro model to evaluate the efficacy against an established microbial infection on catheter surfaces using the same bacteria strains. A >90% reduction in viable bacteria on the catheter surfaces was observed after instilling the 75 mM SNACET lock solution within the lumen of the infected catheter for only 2 h. These findings propound that SNACET lock solution is a promising biocidal agent and demonstrate the initiation of a new platform technology for NO-releasing lock solution therapy for the inhibition and treatment of catheter-related infections.

Impact of Healthcare-Associated Infections Connected to Medical Devices—An Update

“…SNACET has also been used for catheter coating. This catheter provided a 90% reduction in bacterial adhesion, providing a novel idea for tackling CVC infections [65]. Polysaccharides are interesting molecules for antifouling applications.…”

“…A catheter lock solution, taurolidine, has provided promising results among children as taurolidine prevents biofilm formation and has broad-spectrum bactericidal and antifungal activity [47]. Kumar et al (2021) introduced this antimicrobial lock therapy as the best economically viable option. They utilized S-nitroso-N-acetyl-lcysteine ethyl ester (SNACET) as the catheter lock solution as it generates nitric oxide, which manifests antimicrobial properties.…”

Recent Developments in Multifunctional Antimicrobial Surfaces and Applications toward Advanced Nitric Oxide-Based Biomaterials

“…S -Nitroso- N -acetylpenicillamine (SNAP) and S -nitrosoglutathione (GSNO) are two commonly used NO donor species that have been studied for biomaterial applications because of their long-term stability and NO release properties in addition to ease of synthesis, low cost, and excellent biocompatibility (Figure f,g) . Other RSNOs such as S -nitroso- N -acetylcysteine (SNACET) (Figure h) and derivatized molecules such as N -acetyl- S -nitrosopenicillaminyl)- S -nitrosopenicillamine (SNAP-SNAP) have also been synthesized and reported. , NO donors can be incorporated into a polymer matrix via solvent impregnation, non-covalent dispersion, blending of the donor in a polymer, or by covalent immobilization of the NO donor moiety to the polymer backbone (Figure ).…”

Inclusion Complexation of S-Nitrosoglutathione for Sustained NO Release and Reduced Device Infection

“…For example, a one-week release of NO above a flux of 0.5 × 10 -10 mol cm −2 min −1 is obtained by using 0.15 M GSNO + 0.15 M αCD (Figure 6B). In previous studies using nitrite or S-nitrosothiol-based solutions/suspensions as filling solutions of catheters, only less than 2 days of NO release with initial bursts was reported, and the antibacterial efficacy was only assessed with < 24 h of locking using NO donor solutions [20][21][22][23]25]. Given that central line catheters need to be locked for 2 or 3 days to several weeks in hemodialysis and chemotherapy and the GSNO reactivity is higher in the real biological environment containing hemoglobin and other reactive species [29,33,57,69], more steady and sustained NO release from the GSNO-CD solutions is desirable.…”