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.
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