Bacteriophage Can Prevent Encrustation and Blockage of Urinary Catheters by Proteus mirabilis

Jonathan Nzakizwanayo, Aurélie Hanin, Diana R. Alves, Benjamin McCutcheon, Cinzia Dedi, Jonathan Salvage, Karen Knox, Bruce Stewart, Anthony Metcalfe, Jason Clark, Brendan F. Gilmore, Cormac G. M. Gahan, A. Toby A. Jenkins, Brian V. Jones

Proteus mirabilis forms dense crystalline biofilms on catheter surfaces that occlude urine flow leading to serious clinical complications in long-term catheterised patients, but there are presently no truly effective approaches to control catheter blockage by this organism. This study evaluated the potential for bacteriophage therapy to control P. mirabilis infection and prevent catheter blockage. Representative in vitro models of the catheterised urinary tract, simulating a complete closed drainage system as used in clinical practice, were employed to evaluate the performance of phage therapy in preventing blockage. Models mimicking either an established infection, or early colonisation of the catheterised urinary tract, were treated with a single dose of a 3 phage cocktail, and the impact on time taken for catheters to block, as well as levels of crystalline biofilm formation, were measured. In models of established infection phage treatment significantly increased time taken for catheters to block (∼3-fold) compared to untreated controls. However, in models simulating early stage infection phage treatment eradicated P. mirabilis and prevented blockage entirely. Analysis of catheters from models of established infection, 10 hours after phage application, demonstrated that phage significantly reduced crystalline biofilm formation, but did not significantly reduce the level of planktonic cells in the residual "bladder" urine. Taken together, these results show that bacteriophage constitute a promising strategy for the prevention of catheter blockage, but that methods to deliver phage in sufficient numbers and within a key therapeutic window (early infection) will also be important to the successful application of phage to this problem.