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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 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.

SUBMITTER: Gwisai T

PROVIDER: S-EPMC5730268 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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

Gwisai Tinotenda T Hollingsworth Nisha Rosita NR Cowles Sarah S Tharmalingam Nagendran N Mylonakis Eleftherios E Fuchs Beth Burgwyn BB Shukla Anita A

Biomedical materials (Bristol, England) 20170712 4

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, niclosa ...[more]

PMID: 28471351

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Project description:IntroductionAntimicrobial resistance (AMR) is a global public health challenge requiring a global response to which Australia has issued a National Antimicrobial Resistance Strategy. The necessity for continued-development of new effective antimicrobials is required to tackle this immediate health threat is clear, but current market conditions may undervalue antimicrobials. We aimed to estimate the health-economic benefits of reducing AMR levels for drug-resistant gram-negative pathogens in Australia, to inform health policy decision-making.MethodsA published and validated-dynamic health economic model was adapted to the Australian setting. Over a 10-year time horizon, the model estimates the clinical and economic outcomes associated with reducing current AMR levels, by up to 95%, of three gram-negative pathogens in three hospital-acquired infections, from the perspective of healthcare payers. A willingness-to-pay threshold of AUD$15,000-$45,000 per quality-adjusted life-year (QALY) gained and a 5% discount rate (for costs and benefits) were applied.ResultsOver ten years, reducing AMR for gram-negative pathogens in Australia is associated with up to 10,251 life-years and 8924 QALYs gained, 9041 bed-days saved and 6644 defined-daily doses of antibiotics avoided. The resulting savings are estimated to be $10.5 million in hospitalisation costs, and the monetary benefit at up to $412.1 million.DiscussionOur results demonstrate the clinical and economic value of reducing AMR impact in Australia. Of note, since our analysis only considered a limited number of pathogens in the hospital setting only and for a limited number of infection types, the benefits of counteracting AMR are likely to extend well beyond the ones demonstrated here.ConclusionThese estimates demonstrate the consequences of failure to combat AMR in the Australian context. The benefits in mortality and health system costs justify consideration of innovative reimbursement schemes to encourage the development and commercialisation of new effective antimicrobials.

Dataset Information

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

Publications

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

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