ABSTRACT Shunts placed in patients to manage cerebrospinal fluid (CSF) drainage are indispensable in medical practice, however, they are susceptible to infection caused by local microflora leading to high mortality and morbidity. Shunts are generally made of carbon or silicone rich polymers to maintain desirable properties such as flexibility, but these inert polymers offer an attractive refuge for the invading skin flora. Absence of self- protective properties either inherently or in concert with the host’s immune system makes these shunts prone to infection. Most systemic antibiotics fail to penetrate the biofilm architecture and successfully eliminate local device infections leaving shunt replacement (revision) as the only option. Revision procedures, although provisionally effective are plagued by a high recurrence rate (~50%) of infection. To address the above-mentioned challenges, antibiotic impregnated shunt catheters intended to resist microbial colonization have been developed but clear demonstration of their clinical efficacy is absent. Even after wide spread adoption of antibiotic shunts and stringent infection control protocols to manage CSF drainage the problem of shunt infection and associated clinical sequelae persist. The applicants have recognized this important, unmet need and have developed a novel technology intended to improve clinical outcomes. The solution proposed by the applicants can actively reduce microbial colonization on transcutaneous device surfaces long term without compromising physical properties of the device and without the use of toxic pharmaceuticals. The goal of the proposed feasibility studies is to assess safety, efficacy and robustness of the new technology in pre-clinical models. Initial design refinement is proposed to identify prototypes with superior antimicrobial properties as determined by short-term and long-term in vitro tests (including broad spectrum efficacy and cytotoxicity). Subsequently, antimicrobial efficacy and safety end-points will be assessed in the animal model (rabbits) to evaluate the potential of the proposed technology in safely mitigating transcutaneous shunt infections. In vitro and in vivo studies will include appropriate controls including unmodified silicone shunts, antibiotic impregnated shunt catheters (Medtronic ARESTM, Codman Bactiseal and Cook Spectrum) and silver eluting catheters. Reduction in microbial colonization will be measured against control (uncoated) shunt catheter in these studies. The expected outcome of this proof-of-concept phase of the project will be the demonstration of mechanical integrity, safety and antimicrobial efficacy of the new technology in in vitro and in vivo. Demonstration of feasibility will set the stage for further commercial development of the technology.