Antimicrobial catheter lock therapy is practiced to prevent lumenal-sourced infections of central venous catheters. Citrate has been used clinically as an anticoagulant in heparin-free catheter locks. Ethanol has also been widely studied as an antimicrobial lock solution component. This study reports on the synergy of glyceryl trinitrate (GTN) with citrate and ethanol in rapidly eradicating methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, Pseudomonas aeruginosa, and Candida albicans biofilms in an in vitro model for catheter biofilm colonization. GTN has a long history of intravenous use as a hypotensive agent. It is potentially attractive as a component of a catheter lock solution because its physiologic half-life is quite short and its metabolic pathways are known. A lock containing 7% citrate and 20% ethanol required 0.01% GTN to fully eradicate biofilms of all test organisms within 2 h in the model. This GTN concentration is below the levels where clinically significant hypotensive effects are expected.
Central line-associated bloodstream infections (CLABSIs) have declined over the past decade but remain a significant medical problem, with a substantial cost burden to the health care system. There are an estimated 250,000 CLABSIs in the United States (1), with an estimated treatment cost of $45,000 or more per infection (2). Significant portions of CLABSIs annually are associated with hemodialysis treatment (3) and treatment of critically ill patients. CLABSIs that present after the first week of catheterization tend to be associated with colonization of the catheter lumenal surfaces (4, 5) and biofilm formation on those surfaces. Colonizing organisms organize within hours into biofilm structures which can serve as a source of CLABSI and can be highly resistant to eradication by antibiotic treatments. Approaches to reducing lumenal colonization include rigorous provider hygiene and use of antimicrobial swabs when connectors are manipulated. Even with these precautions, much of the lumenal surfaces remain vulnerable to colonization. Another approach to combatting lumenal infections has been the use of antimicrobial lock therapy (ALT). Catheter lumens are hydraulically locked when not in use. Typically, lock solutions include anticoagulants to inhibit the formation of blood clots, which can occlude flow through catheters. Heparin has traditionally been used as an anticoagulant; however, there have been concerns about its purity (6), as well as its potential to promote bacterial biofilm colonization (7). Antimicrobial locks have generally fallen into the categories of antibiotic locks and nonantibiotic, antiseptic locks. Antibiotic locks have been pursued both for catheter salvage and for infection prevention. Antibiotic catheter locks have recently been reviewed (8). Significant issues limiting the use of antibiotic locks for prevention are their higher costs and potential to promote the development of antibiotic resistance. We report here on the utility of glycery...