Biological challenges of phage therapy and proposed solutions: a literature review

ABSTRACT

Introduction: In light of the emergence of antibiotic-resistant bacteria, phage (bacteriophage) therapy has been recognized as a potential alternative or addition to antibiotics in Western medicine for use in humans.

Areas covered: This review assessed the scientific literature on phage therapy published between 1 January 2007 and 21 October 2019, with a focus on the successes and challenges of this prospective therapeutic.

Expert opinion: Efficacy has been shown in animal models and experimental findings suggest promise for the safety of human phagotherapy. Significant challenges remain to be addressed prior to the standardization of phage therapy in the West, including the development of phage-resistant bacteria; the pharmacokinetic complexities of phage; and any potential human immune response incited by phagotherapy.

KEYWORDS:

• Phage
• phage resistance
• endolysin
• phage therapy
• phagotherapy

Article highlights

• Growing antibiotic resistance, in addition to promising historical and current phage studies, has renewed interest in human phagotherapy.

• To expedite consideration of phages as antibacterial agents, certain biological challenges associated with their use should be addressed, including acquired bacterial resistance to phage infection; the pharmacologic complexity of phage relative to small-molecule antibiotics; and the potential for interactions between the human immune system and phage.

• Challenges may be allayed through the use of phage cocktails, phage modifications, encapsulation, and/or enzybiotics.

Acknowledgments

The authors thank Larry J. Prokop, MLS, for his careful search and compilation of source material from several medical databases and support throughout the writing and revision process, and to Kerryl E. Greenwood-Quaintance, MS, proofreading the manuscript.

Declaration of interest

R Patel has research grant support from ContraFect, a company which has a financial interest in the subject matter discussed in this manuscript. In addition, she reports other relationships not directly relevant to the subject matter discussed in this manuscript, including research grant support from CD Diagnostics, Merck, Hutchison Biofilm Medical Solutions, Accelerate Diagnostics, ContraFect, TenNor Therapeutics Limited and Shionogi, serving a consultant to Curetis, Specific Technologies, Next Gen Diagnostics, PathoQuest, Selux Diagnostics and Qvella (all monies are paid to Mayo Clinic), and receiving travel reimbursement from ASM and IDSA, an editor’s stipend from IDSA, and honoraria from the NBME, Up-to-Date and the Infectious Diseases Board Review Course. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplemental material

Supplemental data for this article can be accessed here.

Additional information

Funding

R Patel is supported by UM1 AI104681, R01 AR056647, R01 AI091594, R01 AI134770 and R21 AI125870. K M Caflisch is supported by T32 AR056950.