Phage Therapy for Urinary Tract Infections: Progress and Challenges Ahead

Abstract

Introduction and hypothesis: Urinary tract infection (UTI) treatment is a growing public health concern owing to increasing antimicrobial resistance. Phage therapy, an alternative or adjunctive treatment to antibiotics, has the potential to address this challenge. However, clinical use of phage therapy is hindered by knowledge gaps and inconsistent reporting. The objective was to review the current state of phage therapy for UTIs and highlight research priorities that can optimize phage clinical efficacy.

Methods: Current literature on UTI phage therapy was examined, focusing on the lack of standardized phage susceptibility testing, phage characterization, and microbiological assessments during and after treatment.

Results: Critical areas requiring further investigation include appropriate phage dosing, optimal routes of administration, and the dynamics of phage-host and phage-patient interactions. The influence of the urinary microbiome, including endogenous phages, on treatment outcomes also needs to be better understood. Suggested data collection and reporting standards should be developed and implemented to improve clinical impact of studies examining phage therapy for UTI. Randomized clinical trials are needed to establish efficacy and determine the best practices for clinical use.

Conclusion: Phage therapy is a promising alternative to antibiotics for managing UTIs, especially in the face of rising antimicrobial resistance. To fully realize its potential, however, future research must focus on standardized protocols, dosing strategies, and the role of the urinary microbiome, with an emphasis on rigorously conducted clinical trials. These steps are essential for integrating phage therapy into mainstream UTI treatment regimens.

Keywords: Phage therapy; Urinary phage; Urinary tract infection; Urinary virome.

Fig. 1

Overview of phage life cycle and bacterial interactions with phages and antibiotics. Antibiotic mechanisms of action (black, right side) include inhibition of cell wall synthesis, inhibition of protein expression, inhibition of DNA replication, and inhibition of transcription. To counteract these actions, bacteria antibiotic resistance mechanisms (red, right side) include targeted mutations, enzymatic inactivation, and efflux channels. Phage mechanisms of action against bacteria (black, left side) include attachment, genome injection, replication, assembly, holin/lysin expression, and ultimately lysis. Bacterial resistance mechanisms to phages include receptor mutations and phage defense mechanisms, including CRISPR, restriction of infection, and abortive infection. This figure was generated in Biorender