Bacteriophage Therapy

Originally discovered and used for treatment of infectious diseases in the early 20th century, the concept of bacteriophage therapy has gained new attention in the current era of increasing antimicrobial resistance. Bacteriophage are viruses that attach and internalize genetic material into their bacterial hosts, setting up replicative cycles that lead to cell lysis. UC San Diego has emerged as a leader in the science and clinical application of bacteriophage therapy.

America's First Clinical Phage Therapy Center

The Center for Innovative Phage Applications and Therapeutics (IPATH) was founded at UC San Diego in 2018. iPATH treats patients with life-threatening multidrug-resistant (MDR) infections with phage therapy through the FDA’s compassionate use program. iPATH is also advancing bacteriophage therapy clinical trials so that it can be rigorously evaluated, and if proven efficacious, become more widely available to combat the global superbug crisis. iPATH's first FDA approved phase 1/2 trial is focusing on MDR Staphylococcus aureus infections of ventricular assist devices.

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At the Leading Edge of Bacteriophage Science

Basic science research supported by iPATH and CHARM explores fundamentals aspects of bacteriophage biology with an eye toward improved therapeutics. Bacteriophage were found to use an intricate ‘treadmill’ to move cargo across Pseudomonas bacterial cells, insight that might help in development of designer phage for specific resistant strains. When these bacteripohages phages infect bacteria, they build a spherical compartment in the middle of the host cell, which keeps antiviral enzymes at bay and provides a “safe room” for the viral genome to replicate and complete their lytic life cyce. Our scientists have also studied the evolutionary processes by which bacteriophage acquire the ability to infect new bacterial host targets, and the complex role of phage in shaping microbial communities in the oral cavity, gut and cystic fibrosis lung.

Opportunities and Challenges

Bacteriophages are self-propagating and grow exponentially at the site of infection, lysing bacterial targets while unable to infect host cells thus limiting toxicity. Bacteriophage usually have a very narrow host range, allowing direct targeting of pathogenic bacteria without broadly affecting the normal microbiota. In general, they must be used synergistically with antibiotics or in "cocktails" of several phage to limit selection of resistant bacteria. As they are unlike any drug, new methodologies for detailed pharmacokinetic and pharmacodynamic (PK/PD) studies are needed to understand the optimal dosing concentration as well as frequency, duration, and route of bacteriophage administration.

Phage Clears CF Pneumonia

A cystic fibrosis (CF) patient developed multidrug-resistant Pseudomonas aeruginosa pneumonia with persistent respiratory failure and colistin-induced renal failure. iPATH and CHARM physician-investigators used IV bacteriophage therapy along with systemic antibiotics to resolve the infection without adverse events. The patient underwent a successful bilateral lung transplant 9 months later.

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