A Novel Nonantibiotic Nitroglycerin-Based Catheter Lock Solution for Prevention of Intraluminal Central Venous Catheter Infections in Cancer Patients

Abstract

For long-term central lines (CL), the lumen is the major source of central line-associated bloodstream infections (CLABSI). The current standard of care for maintaining catheter patency includes flushing the CL with saline or heparin. Neither agent has any antimicrobial activity. Furthermore, heparin may enhance staphylococcal biofilm formation. We evaluated the safety and efficacy of a novel nonantibiotic catheter lock solution for the prevention of CLABSI. Between November 2015 and February 2016, we enrolled 60 patients with hematologic malignancies who had peripherally inserted central catheters (PICC) to receive the study lock solution. The study lock consisted of 15 or 30 g/ml of nitroglycerin in combination with 4% sodium citrate and 22% ethanol. Each lumen was locked for at least 2 h once daily prior to being flushed. After enrollment of 10 patients at the lower nitroglycerin dose without evidence of toxicity, the dose was escalated to the higher dose (30 g/ml). There were no serious related adverse events or episodes of hypotension with lock administration. Two patients experienced mild transient adverse events (one headache and one rash) possibly related to the lock and that resolved without residual effect. The CLABSI rate was 0 on lock days versus 1.6/1,000 catheter days (CD) off lock prophylaxis, compared with a rate of 1.9/1,000 CD at the institution in the same patient population. In conclusion, the nitroglycerin-based lock prophylaxis is safe and well tolerated. It may prevent CLABSI when given daily to cancer patients. Large, prospective, randomized clinical trials are needed to validate these findings. (This study has been registered at ClinicalTrials.gov under identifier NCT02577718.) KEYWORDS nitroglycerin, catheter, lock solution, central venous catheter, infections, cancer patients C entral venous catheters (CVC) are imperative for the treatment and management of cancer patients, particularly those with hematological malignancies who require a long-term access for the administration of chemotherapy, antibiotics, blood products, and fluids as well as for frequent blood draws. However, these lifelines are the leading source of bloodstream infections, causing at least 400,000 episodes of bloodstream infections yearly in cancer patients (1) and contributing to up to 62% of the bloodstream infections in patients with long-term CVC (2, 3). These catheter-associated infections constitute a major public health challenge, with an estimated mortality rate of 10 to 25% (4) and estimated cost of $45,000 per episode (5).

Minocycline-EDTA-Ethanol Antimicrobial Catheter Lock Solution Is Highly Effective In Vitro for Eradication of Candida auris Biofilms

“…In a previous clinical catheter salvage study, MEE was 100% clinically effective in salvaging central lines for cancer patients with bacterial CLABSIs (6). In vitro studies showed this combination to be synergistically effective against other Candida species (12).…”

Antimicrobial Efficacy and Safety of a Novel Gas Plasma-Activated Catheter Lock Solution

“…PAD lock solution is free of antibiotics, and the mechanism of action does not involve specific binding sites on bacteria or fungi, thereby minimizing the risk of selecting for antimicrobial resistance (11). In this context, it is interesting that a 2-h exposure to a non-antibiotic-containing, nitroglycerin-based lock solution reduces bacterial and fungal intraluminal biofilms by 4 orders of magnitude (30,31). Nitroglycerin produces reactive oxygen and nitrogen species (32), and this may explain why its activity against bacteria and fungi is of similarly broad spectrum to PAD.…”

Antimicrobial Efficacy and Safety of a Novel Gas Plasma-Activated Catheter Lock Solution

“…PAD lock solution is free of antibiotics and the mechanism of action does not involve specific binding sites on bacteria or fungi, thereby minimizing the risk of selecting for antimicrobial resistance (11). In this context, it is of interest to note that a 2 hour exposure to a non-antibiotic containing, nitroglycerin-based lock solution reduces bacteria and fungal intraluminal biofilms by 4 orders of magnitude (19,34). Nitroglycerin produces reactive oxygen and nitrogen species (35) and this may explain why its activity against bacteria and fungi is similarly broad spectrum to PAD.…”