There is a need for non-antibiotic, antimicrobial compositions with low toxicity capable of broad-spectrum eradication of pathogenic biofilms in food preparation and healthcare settings. In this study we demonstrated complete biofilm eradication within 60 min with synergistic combinations of caprylic and polygalacturonic (PG) acids in an in vitro biofilm eradication model against representative hospital and foodborne infectious pathogen biofilms (methicillin-resistant Staphylococcus aureus, multidrug-resistant Pseudomonas aeruginosa, Candida albicans, Escherichia coli, and Salmonella enteritidis). Antimicrobial synergy against biofilms was demonstrated by quantifying viable organisms remaining in biofilms exposed to caprylic acid alone, PG acid alone, or combinations of the two. The combinations also synergistically inhibited growth of planktonic organisms. Toxicity of the combination was assessed in vitro on L929 fibroblasts incubated with extracts of caprylic and PG acid combinations using the Alamar Blue metabolic activity assay and the Trypan Blue exclusion cell viability assay. The extracts did not produce cytotoxic responses relative to untreated control fibroblasts.

Candida auris poses emerging risks for causing severe central lineassociated bloodstream infections. We tested in vitro the ability of antifungal lock solutions to rapidly eradicate C. auris biofilms. Liposomal amphotericin B, amphotericin B deoxycholate, fluconazole, voriconazole, micafungin, caspofungin, and anidulafungin failed to completely eradicate all 10 tested C. auris biofilms. Conversely, nitroglycerin-citrate-ethanol (NiCE) catheter lock solution completely eradicated all replicates for all of C. auris biofilms tested.

BackgroundCatheter associated urinary tract infections (CAUTIs) are a significant medical issue with substantial morbidities and costs. CAUTIs are primarily caused by colonization of the external surface of Foley catheters which serve as conduits for colonizing microbes to access the bladder. In order to prevent these CAUTIs, we developed a double-cuff Foley catheter with a novel irrigation cuff for daily irrigation of the periurethral space with a biocompatible antimicrobial disinfecting solution. This study assessed the efficacy of this system for reducing external-surface microbial colonization of catheters in an in vitro model.MethodsThe novel double cuff Foley and disinfectant solutions were evaluated in an established in vitro CAUTI model (Gaonkar, et al 2003) where a Foley catheter indwelled in a simulated urethra. 5.5 × 105 CFU of common uropathogens (MRSA, E. coli, C. albicans) were allowed to attach to the external catheter surface at meatal end of the catheter for 2 hours at 37°C. Subsequently, 3 mL of disinfectant solutions were instilled through the irrigation cuff and covered the periurethral catheter surfaces. Catheters were then incubated an additional 24–48 hours at 37°C, removed, cut into segments, and adherent organisms were quantified by sonication. Disinfectant solutions evaluated included various combinations of 1% polygalacturonic acid (PG), 0.4% caprylic acid (CAP) and (dilute) 0.3% H2O2.ResultsFor all organisms tested only the triple combination periurtehral flush (PG+CAP+H2O2) completely prevented biofilm colonization of catheters indicating antimicrobial synergy of the component agents. Control catheters grew >104 CFU/segment. Single agent or double agents combinations were only partially effective in preventing colonization by all three pathogens.ConclusionThe PG + CAP + H2O2 periurethral disinfectant flush instilled through an irrigation cuff in a novel double-cuff Foley catheter was able to completely prevent microbial colonization of the external catheter surface by MRSA, E. coli and C. albicans in an in vitro CAUTI model. In vivo studies are needed to further evaluate this technology for prevention of CAUTI.Disclosures J. Rosenblatt, Infective Technologies, LLC: Co-Inventor of the Nitroglycerin-Citrate-Ethanol catheter lock solution technology which is owned by the University of Texas MD Anderson Cancer Center (UTMDACC) and has been licensed by Novel Anti-Infective Technologies, LLC in which Dr. Rosenblatt is a and Shareholder, Licensing agreement or royalty; UT MD Anderson Cancer Center: Co-Inventor of the Nitroglycerin-Citrate-Ethanol catheter lock solution technology which is owned by the University of Texas MD Anderson Cancer Center (UTMDACC) and has been licensed by Novel Anti-Infective Technologies, LLC in which Dr. Rosenblatt is a s and Scientific Advisor, Licensing agreement or royalty; I. Raad, Merck: Grant Investigator, Research grant; Allergan: Grant Investigator, Research grant; Infective Technologies, LLC: Co-Inventor of the Nitroglycerin-Citrate-Ethanol cathet...

Candida auris is an emerging pathogen that can cause virulent central-line-associated bloodstream infections. Catheter salvage through the eradication of biofilms is a desirable therapeutic option. We compared taurolidine and minocycline-EDTA-ethanol (MEE) catheter lock solutions in vitro for the eradication of biofilms of 10 C. auris strains. MEE fully eradicated all C. auris biofilms, while taurolidine lock partially eradicated all of the C. auris biofilms. The superiority was significant for all C. auris strains tested (P = 0.002).

CAUTI remains a serious healthcare issue for incontinent patients whose urine drainage is managed by catheters. A novel double-balloon Foley catheter was developed which was capable of irrigating the extraluminal catheter surfaces within the periurethral space between the urethral-bladder junction and meatus. The catheter has a retention cuff that is inflated to secure the catheter in the bladder and a novel irrigation cuff proximal to the urethral-bladder junction capable of providing periurethral irrigation from the urethral-bladder junction to the meatus. Uniform periurethral irrigation was demonstrated in an ex vivo porcine model by adding a dye to the antimicrobial urethral irrigation solution. An in vitro biofilm colonization model was adapted to study the ability of periurethral irrigation with a newly developed antimicrobial combination consisting of polygalacturonic acid + caprylic acid (PG + CAP) to prevent axial colonization of the extraluminal urethral indwelling catheter shaft by common uropathogens. The extraluminal surface of control catheters that were not irrigated formed biofilms along the entire axial urethral tract after 24 hours. Significant (p<0.001) inhibition of colonization was seen against multidrug-resistant Pseudomonas aeruginosa (PA), carbapenem-resistant Escherichia coli (EC), and carbapenem-resistant Klebsiella pneumoniae (KB). For other common uropathogens including Candida albicans (CA), Proteus mirabilis (PR), and Enterococcus faecalis (EF), a first irrigation treatment completely inhibited colonization of half of the indwelling catheter closest to the bladder and a second treatment largely disinfected the remaining intraurethral portion of the catheter towards the meatus. The novel Foley catheter and PG + CAP antimicrobial irrigant prevented biofilm colonization in an in vitro CAUTI model and merits further testing in an in vivo CAUTI prevention model.