# The Safety and Efficacy of Phage Therapy: A Systematic Review of Clinical and Safety Trials

## TL;DR

This paper reviews clinical trials of phage therapy and finds it is safe but often ineffective due to improper phage delivery or bacterial resistance.

## Contribution

The study systematically analyzes why phage therapy trials have failed to show efficacy, identifying key requirements for successful treatment.

## Key findings

- Modern phage therapy trials consistently report safety but limited efficacy.
- Efficacy requires delivering the right phage to the right place in sufficient quantity.
- Historical trials lacked evidence of both safety and efficacy.

## Abstract

Trials of phage therapy have not consistently reported efficacy. This contrasts with promising efficacy rates from a sizeable and compelling body of observational literature. This systematic review explores the reasons why many phage trials have not demonstrated efficacy. Four electronic databases were systematically searched for safety and/or efficacy trials of phage therapy. Sixteen trials of phage therapy were included, in which 378 patients received phage. These were divided into historical (pre-2000; N = 3; n = 76) and modern (post-2000; N = 13; n = 302) trials. All 13 modern trials concluded that phage therapy was safe. Six of the 13 modern trials were exclusively safety trials. Seven modern trials investigated both safety and efficacy; efficacy was observed in two. Two of three historical trials did not comment on safety, while adverse effects in the third likely reflected the use of phage preparations contaminated with bacterial debris. None of the historical trials contained evidence of efficacy. The evidence from trials is that phage therapy is safe. For efficacy to be observed a therapeutic amount of the right phage(s) must be delivered to the right place to treat infections containing enough susceptible bacterial cells. Trials that have not demonstrated efficacy have not fulfilled one or more elements of this principle.