Background: There has been renewed interest in phages amidst growing antimicrobial resistance. Their potential for intestinal decolonisation is interesting because of their specificity, minimal side effects, and microbiota preservation. In addition, phage-resistant bacterial mutants that arise during treatment may become more susceptible to antibiotics and less virulent, possibly leading to better clinical outcomes.

Objectives: This study's primary objective is to measure the efficacy of phage-based intestinal decolonisation of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp) at 14 days post-treatment, as well as its feasibility, which is defined as >80% achieving at least 7 days of treatment. Secondary objectives will include phage safety at 14 days post-treatment, intestinal KPC-Kp load changes over time, characterisation of phage-resistant KPC-Kp mutants, microbiome changes, infection-related outcomes, and general clinical outcomes 3 months after the end of treatment.

Methods: This feasibility and proof-of-concept study aims to include 15 high-risk patients recruited from a tertiary hospital in São Paulo who will receive individualised phage combinations for a mean duration of 14 days. Safety data will be reviewed by an independent Safety Monitoring Board. Description of microbiological techniques is provided.

Conclusions: To the best of our knowledge, this is the first published protocol that aims to establish a standardised, individualised phage-treatment framework for intestinal decolonisation in a high-endemic setting. It will also explore phage-bacterial interactions and their broader impact on bacterial virulence and susceptibility profiles. It represents a stepping stone towards implementing phage therapy in South America and bringing knowledge and capacities to the countries most impacted by escalating antimicrobial resistance.