Phage therapy: from basic biology to clinical application

Bacteriophages have been applied therapeutically for more than a century for the management of bacterial infections in humans. Although their potential as a safe alternative or adjunct to antibiotics is well established, clinical success is difficult to predict from in vitro testing. There is currently no consensus on the optimal way to use them, nor are there any simple extrapolations from the use paradigms of conventional antibiotics. A rational approach to phage therapy requires informed phage selection and a comprehensive understanding of bacterial-phage-human host relationships and the management of bacterial and phage adaptations that occur in vivo. Phages may be used in ways that antibiotics are not and are a powerful approach for addressing the problem of antimicrobial resistance, not least because their optimal use requires a more thoughtful approach. In this Review, we explore key aspects of phage biology that underpin the effective use of phages for therapy. We outline clinical strategies for applying phages against a range of infections, highlighting their advantages and limitations. We then address challenges in production, scalability and regulation of phage preparations, identifying areas requiring further development. Finally, we discuss interactions between phages and the human immune system, and their importance for therapeutic success.