In Vitro and In Vivo activity of a novel catheter lock solution against bacterial and fungal biofilms [PublishAheadOfPrint]

Central line associated bloodstream infections (CLABSIs) are increasingly recognized to be associated with intralumenal microbial biofilms, and effective measures for the prevention and treatment of BSI remain lacking. This report evaluates a new commercially developed antimicrobial catheter lock solution (ACL) containing trimethoprim (5 mg/ml) and ethanol (25%) and calcium Ethylenediaminetetraacetic acid (CA-EDTA) 3% for activity against bacterial and fungal biofilms using in vitro and in vivo (rabbit) catheter biofilm models. Biofilms were formed with bacterial (seven different species including vancomycin-resistant enterococcus, VRE) or fungal (C. albicans) species on catheter materials. Biofilm formation was evaluated by quantitative culture (colony forming units, CFUs) and scanning electron microscopy (SEM). Treatment with ACL inhibited growth of adhesion phase biofilms in vitro 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. In the catheterized rabbit model, when compared against heparinized saline control, ACL lock therapy significantly reduced the catheter bacterial (3.49 ± 0.75 vs. 0.03 ± 0.06 log CFU/catheter, respectively; P = 0.016) and fungal burden (2.48 ± 1.60 vs. 0.55 ± 1.19 log CFU/catheter segment, respectively; P = 0.013). SEM also demonstrated eradication of bacterial and fungal biofilms in vivo on catheters exposed to ACL, while vigorous biofilms were observed on untreated control catheters. Our results demonstrate that ACL was efficacious against both adhesion phase and mature biofilms formed by bacteria and fungi in vitro as well as in vivo.

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