Emerging medical and engineering strategies for the prevention of long-term indwelling catheter blockage

Abstract

Urinary catheters have been used on an intermittent or indwelling basis for centuries, in order to relieve urinary retention and incontinence. Nevertheless, the use of urinary catheters in the clinical setting is fraught with complication, the most common of which is the development of nosocomial urinary tract infections, known as catheter-associated urinary tract infections. Infections of this nature are not only significant owing to their high incidence rate and subsequent economic burden but also to the severe medical consecutions that result. A range of techniques have been employed in recent years, utilising various technologies in attempts to counteract the perilous medical cascade following catheter blockage. This review will focus on the current advancement (within the last 10 years) in prevention of encrustation and blockage of long-term indwelling catheters both from engineering and medical perspectives, with particular emphasis on the importance of stimuli-responsive systems.

Innovations in indwelling urethral catheterisation

“…Anti‐microbial strategies include: passive antimicrobial release (typically by impregnation into the catheter surface or by incorporation in a hydrogel catheter coating) and non‐release contact killing (by antimicrobial compounds covalently anchored to the catheter material) . Antifouling materials or designs prevent bacterial adhesion using non‐antimicrobial approaches, such as mechanical methods or unfavourable surface topography or chemistry . Many products have been subject to in vitro testing but have not transitioned to clinical trials or use.…”

“…The primary limitations of passive antimicrobial release include the inevitable loss of therapeutic activity after depletion of the active agent from the catheter, as well as acceleration of antibiotic resistance due to sublethal doses. The development of nanoscale antimicrobials may aid with sustained active agent release . Contact killing is an alternative to passive release‐based strategies and involves covalent bonding of antimicrobial substances to the catheter surface, thus avoiding issues of reservoir depletion .…”

“…The development of nanoscale antimicrobials may aid with sustained active agent release . Contact killing is an alternative to passive release‐based strategies and involves covalent bonding of antimicrobial substances to the catheter surface, thus avoiding issues of reservoir depletion . Novel non‐antibiotic therapies that would avoid antibiotic resistance are also under investigation for incorporation in catheter coatings, such as bacteriophages (natural viral predators of bacteria) and quorum‐sensing inhibitors (counteract bacterial communication processes within biofilm) .…”

“…The Sharklet micropattern outperformed control catheters to reduce Escherichia coli colonisation in vitro and reduce biofilm formation but not CAUTI in a first‐in‐man open‐label randomised controlled trial (RCT) . Other antifouling strategies are not yet commercially available, such as hydrophilic materials (e.g., poly(ethylene glycol) brushes), polyzwitterions (neutral molecules containing equal positive and negative charge), and nanostructured materials .…”

“…Half of patients with long‐term indwelling urinary catheters will experience catheter blockage . Catheter blockage is the result of urine infection with urease‐producing organisms, predominantly Proteus mirabilis . Urease generates ammonium and thereby elevates urinary pH, leading to the precipitation of struvite (magnesium ammonium phosphate) and apatite (calcium phosphate) to form a crystalline biofilm, which encrusts and blocks the urinary catheter.…”