h Proteus mirabilis forms dense crystalline biofilms on catheter surfaces that occlude urine flow, leading to serious clinical complications in long-term catheterized 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 catheterized 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 colonization of the catheterized 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, was measured. In models of established infection, phage treatment significantly increased time taken for catheters to block (ϳ3-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 h 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.A frequent complication associated with long-term urethral catheterization is the encrustation and blockage of catheters due to infection with Proteus mirabilis, which can be isolated from around 45% of catheter-associated urinary tract infections (CAUTI) (1, 2). Blockage stems from the ability of P. mirabilis to form dense biofilms on catheter surfaces and the production of a potent urease enzyme which generates ammonia through hydrolysis of urea (1,3,4). Ammonia production elevates urinary pH, causing the precipitation of calcium and magnesium phosphates and the subsequent formation of crystals which become trapped within developing biofilms (1, 5). Once embedded in the biofilm, crystal growth is stabilized and enhanced by the biofilm matrix (6, 7). As this process continues, the biofilm gradually becomes mineralized, leading to development of extensive crystalline biofilm structures which ultimately block catheters (1, 5). If blockage is unnoticed, it can lead to reflux of infected urine to the upper urinary tract and the onset of serious clinical complications, including pyelonephritis, septicemia, and shock (1, 8).Although catheters containing antimicrobial coatings are currently available, their efficacy in preventing infection during even short-term use remains questionable, and all...