A Retrospective, Observational Study of 18 Cases of Expanded Access Phage Therapy
Austen Terwilliger 1,2, Sabrina Green 3, Justin Clark 1,2, Haroldo Santos 2, Kyle Weesner 1,2, Keiko Salazar 1,2, Saima Aslam 4, J. William Campbell 5, Sarah Doernberg 6, Emily Blodget 7, Michele Morris 8, Gina Suh 9, Karam Obeid 10, Fernanda Silveira 11, Claire Bocchini 12, John Reynolds 13, Julie Katkin 14, Lindsey Cameron 14, Jenny Aronson 15, Andrea Censullo 16, Andrey Filippov 17, Katrine Whiteson 18, Barbara Trautner 19,20, Anthony Maresso 1,2
- TAILΦR Labs, Baylor College of Medicine, Houston, Texas
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas
- Department of Biosystems, Lab of Gene Technology, KU Leuven, Leuven, Belgium
- Division of Infectious Diseases and Global Public Health, Center for Innovative Phage Applications and Therapeutics, University of California, San Diego, La Jolla, California
- Division of Infectious Diseases and Infection Prevention, St. Luke’s Hospital, Chesterfield, Missouri
- Department of Medicine, Division of Infectious Diseases, University of California, San Francisco, California
- Department of Medicine Keck Medical Center of USC. Los Angeles, California
- Division of Infectious Diseases, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida
- Division of Infectious Diseases, Department of Medicine, Mayo Clinic, Rochester, Minnesota
- University of Minnesota, Department of Medicine, Division of Infectious Diseases and International Medicine, Minneapolis, Minnesota
- University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
- Pediatric Infectious Diseases, Baylor College of Medicine, Houston, Texas
- Department of Medicine, Duke University School of Medicine
- Texas Children’s Hospital, Houston, Texas
- Infectious Diseases, Stanford Medicine, Redwood City, California
- Infectious Diseases, Kaiser Permanente, Panorama City, California
- Wound Infections Department, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland
- Department of Molecular Biology and Biochemistry, University of California, Irvine
- Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
- Department of Medicine, Baylor College of Medicine, Houston, Texas
Austen Terwilliger terwilli@bcm.edu
The emergence of antibiotic resistance is threatening to undermine modern medicine. Dire predictions claim 10 million deaths per year by 2050 at a cost of trillions to governments and healthcare. The problem is compounded by the inherent adaptability of bacteria in the face of intense selective pressures.
Bacteriophages have been proposed as a possible solution for this crisis. Here, we detail progress following the formation of TAILΦR, a phage center that provides personalized treatment for compassionate-use cases. We report the discovery, characterization, pipeline, and process of phage selection and purification, as well as clinical course and outcomes.
TAILΦR responded to 92 requests for a phage hunt, for which we received 86 clinical isolates and generated 217 novel phages against 12 bacterial species. Most common indications requested were urinary tract infection/prostatitis, left-ventricular assist device infections, and bacteremia. From those 86 cases, 18 patients received treatment. Several patients demonstrated bacterial eradication (8/18) and/or clinical improvement (10/18) up to a year post-treatment.
The true potential of phage therapy will not be realized until discovery, manufacturing, and regulatory efforts harmonize to rapidly deliver personalized cocktails in a manner that curtails real-time evolution. TAILΦR is addressing barriers by developing good manufacturing practices (GMP) to significantly reduce time-to-treatment and curating cocktails that anticipate bacterial resistance. Worldwide networks of phage centers will fill a critical treatment void while fueling antibacterial innovation for the most complex and challenging patient cases. This work was funded by U19 AI157981, Robert and Helen Kleberg Foundation, Mike Hogg Foundation, and BCM seed funds awarded to A.M.