Drug Repurposing as an approach to control biofilm formation and encrustation of urinary catheters: Preclinical evidence and future challenges

Indwelling urethral catheters are the most widely used medical devices across the world, and catheter-associated urinary tract infections (CAUTIs) are the most common type of healthcare acquired infection. For many patients, urinary catheter blockage is a common and recurring problem, which can have considerable negative impact on patient health and well-being. Blockage primarily stems from the formation of crystalline bacterial biofilms on catheter surfaces, which can lead to upper urinary tract infection (UTI) and the onset of serious clinical complications. Potential solutions to this important clinical problem include the development of novel antibiofilm agents that can prevent formation of these communities on urinary catheters. However, traditional de novo methods of drug discovery are laborious, expensive, have long lead times and carry a high risk of failure in the clinical trial stages. One potential approach to mitigate this risk and cost, is the evaluation of pre-existing licensed drugs for those with useful antibiofilm or antimicrobial activity. Here we review current preclinical evidence for antibiofilm and antimicrobial activities in licensed drugs from a range of classes, such as urease inhibitors, Selective Serotonin Reuptake Inhibitors (SSRIs), phenothiazines, oncology therapeutics and non-steroidal anti-inflammatory drugs (NSAIDs). In doing so, we consider the application of the repurposing approach to control CAUTI and catheter blockage, and identify key challenges and opportunities related to delivery of repurposed drugs to the catheterised urinary tract.