Standardised Treatment And Monitoring Protocol to assess safety and tolerability of phage therapy in adults and children (STAMP study)

A standardised treatment and monitoring protocol for bacteriophage therapy. Duration and route of administration of phage will be determined individually for each patient by the principal investigator and will depend on the site of infection, confirmed or suspected pathogens, patient factors (e.g. immune compromise, IV access) and availability of phage products (e.g. formulation, purification). The first two weeks of intravenous phage therapy will be administered in hospital. If phage therapy is planned for longer than two weeks, further treatment can be administered via “Hospital in the Home”-like services. Purely topical, aerosolised or oral/enteral administration of phage can occur in the outpatient setting. For intravenously administered phage, the dose will be determined by the endotoxin level of the phage product, keeping below accepted human pyrogenic threshold of 5 EU/kg per dose. Within this limit, the aim is to administer at least 10^9 pfu/dose. If a non-intravenous route is selected as the primary route of administration (e.g. nebulised, oral/enteral, topical), the aim is to administer at least 10^10 pfu/dose. Multiple routes of administration may be appropriate for individual patients. The phage will be administered once daily in the morning for the first 2 days and then twice daily for the next 12 days. For critically unwell patients, initial twice daily dosing may be used (i.e. from day 1). For patients planned to receive phage therapy for longer than 14 days, dosing frequency will be determined taking into consideration practical limitations. For patients receiving only non-systemically administered phage products these will be administered once daily throughout the course. Invasive routes of administration (e.g. intra-articular or endobronchial), will be considered additional to the primary route of administration. Patients receiving 14 days of intravenous or oral/enteral phage therapy (majority of participants), monitoring of blood and other clinical samples will be performed on days 0 (baseline), 2, 4, 8, 11, 15 and 29. Monitoring will include inflammatory and immune responses to phage therapy, microbiological clearance and microbiome changes, and phage kinetics. For patients receiving only non-systemically administered phage products, monitoring of blood and other clinical samples will be performed on days 0 (baseline), 2, 4, 8, 15 and 29 but will not include monitoring of phage kinetics. Phage kinetics will be used to adjust dosing frequency for intravenous and orally administered phage: on once daily treatment if the pre-dose serum phage level by plaque assay is <10^2 pfu/mL, the dose will be increased to twice daily, otherwise continue once daily dosing; on twice daily treatment if the pre-dose serum phage level by plaque assay is >10^2 pfu/mL, the dose will be reduced to once daily, otherwise twice daily dosing will continue. For patients planned to receive longer than 14 days of therapy, ongoing monitoring will be performed on a monthly basis until 1 month after the end of phage therapy. A self-complete quality-of-life questionnaire (EQ-5D-5L/EQ-5D-Y) will be sent to participants on days 0 (baseline) and 29, and again at 3 and 6 months (from start of phage therapy). For patients receiving longer than 3 months of phage therapy, the survey link will also be sent out at 12 months.