Abstract

Nosocomial infections caused by antibiotic-resistant bacteria are constantly growing healthcare threats, as they are the reason for the increased mortality, morbidity, and considerable financial burden due to the poor infection outcomes. Indwelling medical devices, such as urinary catheters, are frequently colonized by bacteria in the form of biofilms that cause dysfunction of the device and severe chronic infections. The current treatment strategies of such device-associated infections are impaired by the resistant pathogens but also by a risk of prompting the appearance of new antibiotic-resistant bacterial mechanisms. Herein, the one-step sonochemical synthesis of hybrid poly(sulfobetaine) methacrylate/Polymyxin B nanoparticles (pSBMA@PM NPs) coating was employed to engineer novel nanoenabled silicone catheters with improved antifouling, antibacterial, and antibiofilm efficiencies. The synergistic mode of action of nanohybridized zwitterionic polymer and antimicrobial peptide led to complete inhibition of the nonspecific protein adsorption and up to 97% reduction in Pseudomonas aeruginosa biofilm formation, in comparison with the pristine silicone. Additionally, the bactericidal activity in the hybrid coating reduced the free-floating and surface-attached bacterial growth by 8 logs, minimizing the probability for further P. aeruginosa spreading and host invasion. This coating was stable for up to 7 days under conditions simulating the real scenario of catheter usage and inhibited by 80% P. aeruginosa biofilms. For the same time of use, the pSBMA@PM NPs coating did not affect the metabolic activity and morphology of mammalian cells, demonstrating their capacity to control antibiotic-resistant biofilm-associated bacterial infections.

Highlights

  • The use of implantable medical devices such as indwelling urinary catheters is imperative in the field of modern medicine for managing urinary retention and incontinence in hospitalized patients [1]

  • Silicone catheters were introduced into the clinical practice as a more efficient alternative to the latex materials, the rapid formation of the so-called conditioning layer composed of nonspecifically attached proteins that serve as anchoring spots for establishing resistance to the host defenses, and conventional antibiotic biofilm structure limits their long-term utilization [8]

  • The engineered nanoenabled coatings showed increased hydrophilicity and reduced protein adsorption, important parameters governing the initial steps of sessile bacterial growth on indwelling medical devices

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Summary

Introduction

The use of implantable medical devices such as indwelling urinary catheters is imperative in the field of modern medicine for managing urinary retention and incontinence in hospitalized patients [1]. Urinary catheters are a predisposing factor for bacterial colonization and the formation of antibiotic-resistant biofilms, causing difficult-to-treat, healthcareassociated infections (HAI) and prolonged hospitalization [2]. The tethered GA residues were activated by laccase to phenoxy radicals, triggering an enzymatically initiated radical polymerization of zwitterionic sulfobetaine methacrylate monomers on the silicone catheters [13]. These strategies are effective in diminishing the biofilm establishment on the surface, they do not aim to kill the pathogens, and the threat of spreading and infection occurrence may still persist

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