Repurposing niclosamide as a versatile antimicrobial surface coating against device-associated, hospital-acquired bacterial infections

Abstract

Device-associated and hospital-acquired infections remain amongst the greatest challenges in regenerative medicine. Furthermore, the rapid emergence of antibiotic resistance and lack of new classes of antibiotics has made the treatment of these bacterial infections increasingly difficult. The repurposing of Food and Drug Administration (FDA) approved drugs for antimicrobial therapies is a powerful means of reducing the time and cost associated with drug discovery and development. In this work, niclosamide, a commercially available anthelmintic drug with recently identified antimicrobial properties, was found to prevent and combat existing biofilms of several relevant Gram-positive bacteria, namely strains of Staphylococcus aureus, including methicillin resistant S. aureus (MRSA), and Staphylococcus epidermidis, all common causes of hospital-acquired and device-associated infections. This anti-biofilm activity was demonstrated at niclosamide concentrations as low as 0.01 μg/mL. We then assessed niclosamide activity as an antibacterial coating, which could potentially be applied to medical device surfaces. We developed solvent cast niclosamide coatings on a variety of surfaces common amongst medical devices including glass, titanium, stainless steel, and aluminum. Niclosamide-coated surfaces exhibited potent in vitro activity against S. aureus, MRSA, and S. epidermidis. At niclosamide surface concentrations as low as 1.6 × 10−2 μg/mm2, the coatings prevented attachment of these bacteria. The coatings also cleared bacteria inoculated suspensions at niclosamide surface concentrations of 3.1 × 10−2 μg/mm2. Hemolysis was not observed at any of the antimicrobial coating concentrations tested. We report a facile, effective means of coating devices with niclosamide to both clear and prevent biofilm formation of common bacteria encountered in hospital-acquired and device-associated infections.

Synergistic Activity of Niclosamide in Combination With Colistin Against Colistin-Susceptible and Colistin-Resistant Acinetobacter baumannii and Klebsiella pneumoniae

“…Niclosamide has also been identified as a potent anti-bacterial drug against Helicobacter pylori (Tharmalingam et al, 2018 ) and Pseudomonas aeruginosa by the inhibition of quorum sensing and various virulence genes, and by the reduction of elastase and pyocyanin levels (Imperi et al, 2013 ; Costabile et al, 2015 ). Moreover, Rajamuthiah et al, have reported that niclosamide present bacteriostatic activity against Staphylococcus aureus probably due the damage in their bacterial membrane but not against A. baumannii, P. aeruginosa, E. coli , and K. pneumoniae (Rajamuthiah et al, 2015 ; Gwisai et al, 2017 ). Currently there is no study regarding the combination between colistin and niclosamide to restore the activity of colistin against Gram-negative bacilli.…”

Anidulafungin liposome nanoparticles exhibit antifungal activity against planktonic and biofilm Candida albicans

“…Hemolytic activity of the anidulafungin liposome and free drug was examined as previously described (Gwisai et al, 2017; Liu et al, 2019). Briefly, bRBCs (10% [vol/vol] suspension in PBS) were incubated with 1×, 5×, and 10× anidulafungin liposomes (10% vol/vol), equivalent free drug concentrations, and a 1% DMSO control in a 96‐well plate for 1 hr at 37°C with gentle rocking.…”

Niclosamide, a Drug with Many (Re)purposes

“…Niclosamide has also shown antimicrobial activities against various bacterial infections such as methicillin‐resistant Staphylococcus aureus (MRSA), tuberculosis (TB), and anthrax . In a drug repurposing study using a library of FDA‐approved drugs, niclosamide was found to specifically inhibit growth of Gram‐positive bacteria and to display strong in vivo and in vitro activities against MRSA (MIC=0.125 μg mL −1 ) .…”

“…Such findings showed that niclosamide is as effective as vancomycin, the current drug of choice for treating MRSA . Subsequently, niclosamide was investigated for its potential as an antimicrobial surface coating against device‐associated and hospital‐acquired infections . Highly versatile niclosamide‐based antimicrobial coatings were developed and were shown to clear existing infections and prevent biofilm formation at very low concentrations …”