<i>In Vitro</i> and <i>In Vivo</i> 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 <i>in vitro</i> and <i>in vivo</i> (rabbit) catheter biofilm models. Biofilms were formed by bacterial (seven different species, including vancomycin-resistant <i>Enterococcus</i> [VRE]) or fungal (<i>Candida albicans</i>) 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 <i>in vitro</i> 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; <i>P</i> = 0.016) and fungal (2.48 ± 1.60 versus 0.55 ± 1.19 log CFU/catheter segment; <i>P</i> = 0.013) burdens in the catheterized rabbit model. SEM also demonstrated eradication of bacterial and fungal biofilms <i>in vivo</i> 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 <i>in vitro</i> and <i>in vivo</i>.