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Repurposing niclosamide as a versatile antimicrobial surface coating against
device-associated, hospital-acquired bacterial infections
#MMPMID28471351
Gwisai T
; Hollingsworth NR
; Cowles S
; Tharmalingam N
; Mylonakis E
; Fuchs BB
; Shukla A
Biomed Mater
2017[Jul]; 12
(4
): 045010
PMID28471351
show ga
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 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 the
formation of, 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 ?g ml(-1). 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) ?g
mm(-2), the coatings prevented attachment of these bacteria. The coatings also
cleared bacteria inoculated suspensions at niclosamide surface concentrations of
3.1 × 10(-2) ?g mm(-2). 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.
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