# Optimization of bacteriophage therapy for difficult-to-treat musculoskeletal infections: a bench-to-bedside perspective

## TL;DR

This paper presents a standardized protocol for using bacteriophages to treat musculoskeletal infections, aiming to improve safety and effectiveness.

## Contribution

The study introduces a multidisciplinary, standardized bench-to-bedside protocol for optimizing phage therapy in musculoskeletal infections.

## Key findings

- A standardized phage therapy treatment pathway was established to ensure data quality and consistency.
- A testing platform was developed to study phage safety, efficacy, and bacterial resistance dynamics.
- Genome sequencing of bacterial isolates helps monitor phage resistance emergence.

## Abstract

Given the increasing threat of antimicrobial resistance, scientists are urgently seeking adjunct antimicrobial strategies, such as phage therapy (PT). However, despite promising results for the treatment of musculoskeletal infections in our center, crucial knowledge gaps remain. Therefore, a prospective observational study (PHAGEFORCE) and a multidisciplinary approach was set up to achieve and optimize standardized treatment guidelines. At our center, PT is strictly controlled and monitored by a multidisciplinary taskforce. Each phage treatment follows the same pathway to ensure standardization and data quality. Within the PHAGEFORCE framework, we established a testing platform to gain insight in the safety and efficacy of PT, biodistribution, phage kinetics and the molecular interaction between phages and bacteria. The draining fluid is collected to determine the phage titer and bacterial load. In addition, all bacterial isolates are fully characterized by genome sequencing to monitor the emergence of phage resistance. We hereby present a standardized bench-to-bedside protocol to gain more insight in the kinetics and dynamics of PT for musculoskeletal infections.