In Vitro and In Vivo Activity of a Novel Catheter Lock Solution against Bacterial and Fungal Biofilms

Abstract

Central-line-associated bloodstream infections are increasingly recognized to be associated with intraluminal microbial biofilms, and effective measures for the prevention and treatment of bloodstream infections remain lacking. This report evaluates a new commercially developed antimicrobial catheter lock solution (ACL), containing trimethoprim (5 mg/ml), ethanol (25%), and calcium EDTA (Ca-EDTA) (3%), for activity against bacterial and fungal biofilms, using and (rabbit) catheter biofilm models. Biofilms were formed by bacterial (seven different species, including vancomycin-resistant [VRE]) or fungal () species on catheter materials. Biofilm formation was evaluated by quantitative culture (CFU) and scanning electron microscopy (SEM). Treatment with ACL inhibited the growth of adhesion-phase biofilms after 60 min (VRE) or 15 min (all others), while mature biofilms were completely inhibited after exposure for 2 or 4 h, compared to control. Similar results were observed for drug-resistant bacteria. Compared to the heparinized saline controls, ACL lock therapy significantly reduced the catheter bacterial (3.49 ± 0.75 versus 0.03 ± 0.06 log CFU/catheter; = 0.016) and fungal (2.48 ± 1.60 versus 0.55 ± 1.19 log CFU/catheter segment; = 0.013) burdens in the catheterized rabbit model. SEM also demonstrated eradication of bacterial and fungal biofilms on catheters exposed to ACL, while vigorous biofilms were observed on untreated control catheters. Our results demonstrated that ACL was efficacious against both adhesion-phase and mature biofilms formed by bacteria and fungi and.

Candida spp./Bacteria Mixed Biofilms

“…Lown et al reported that a lock solution with micafungin, ethanol, and doxycycline inhibited C. albicans and mixed C. albicans-S. aureus biofilms. Beforehand, it was also confirmed the great in vitro activity of the same drugs as single agents for the prevention and treatment of C. albicans biofilms [177][178][179][180]. In this recent work, it was reported that a solution with 2% (v/v) ethanol, 0.01565 µg/mL micafungin, and 800 µg/mL doxycycline reduced metabolic activity (98%), with no fungal regrowth, applied once to prevent fungal biofilm formation.…”

Tetrasodium EDTA Is Effective at Eradicating Biofilms Formed by Clinically Relevant Microorganisms from Patients’ Central Venous Catheters

“…Recently, a 4% tetrasodium ethylenediamine tetraacetic acid (EDTA) lock solution was approved by Health Canada to maintain patency and decrease the risk of bacterial colonization and biofilm formation within CVADs. EDTA has been used for decades as a powerful anticoagulant preventing clot formation in vitro ( 22 , 23 ) and is still being used in this capacity today ( 24 ). However, the form of EDTA most often used is the disodium salt, which has reduced antimicrobial properties ( 25 ).…”

Comparative efficacy of various antimicrobial lock solutions for preventing catheter-related bloodstream infections: A network meta-analysis of 9099 patients from 52 randomized controlled trials

“…However, the CLS with ethanol that reduced the incidence of CRBSI has also been shown to sterilize biofilms of gram-positive and gram-negative bacteria and fungal pathogens in vitro. Therefore, ethanol at low concentrations for a short time has higher efficacy than conventional antibiotics at high concentrations for a long period to treat CRBSI (Qu et al, 2009;Chandra et al, 2018).…”