Phage therapy offers an alternative approach to treating bacterial infections, particularly as conventional treatments become less effective. This strategy utilizes naturally occurring viruses called bacteriophages, or “phages,” which specifically target and destroy bacteria. Phages combat infectious diseases, holding potential for complex infections that resist standard antibiotic interventions.
Understanding Phage Therapy
Bacteriophages are viruses that exclusively infect bacteria, making them distinct from viruses that target human cells. They are among the most abundant biological entities on Earth, found in diverse environments from soil to the human gut. Each phage targets only one or a few specific strains of bacteria, contributing to their precise action.
When a bacteriophage encounters a susceptible bacterium, it initiates a process called the lytic cycle, which ultimately leads to the destruction of the bacterial cell. The cycle begins with attachment, where the phage binds to specific receptors on the bacterial cell. The phage then penetrates the bacterial cell wall and membrane, injecting its genetic material, either DNA or RNA, into the host.
Once inside, the phage genetic material hijacks the bacterium’s cellular machinery, redirecting it to produce new phage components like DNA and proteins. These parts then assemble into mature phage particles within the host cell. The final stage is lysis, where assembled phages produce enzymes that rupture the bacterial cell wall, releasing new phages. These released phages can then infect other bacteria.
The Rise of Antibiotic Resistance
The widespread use of antibiotics has led to antibiotic resistance. Bacteria, through natural selection and genetic mutations, can evolve mechanisms to survive exposure to antibiotics that would normally kill them. This acquired resistance can then spread among different bacterial species, making infections increasingly difficult to treat.
Overuse and misuse of antibiotics drive this resistance. Prescribing antibiotics for viral infections, for which they are ineffective, or patients not completing their full course of medication contributes to the problem. When bacteria are exposed to insufficient or inappropriate antibiotic levels, resistant strains survive and multiply, leading to a rise in multi-drug resistant “superbugs.”
The consequences of antibiotic resistance include higher treatment costs, longer hospital stays, and increased mortality rates. Infections once easily treatable, such as urinary tract infections, pneumonia, and bloodstream infections, now pose significant challenges. This highlights the need for new treatment options beyond traditional antibiotics.
Navigating Phage Therapy in the United States
Phage therapy is not yet widely available in the United States, and no bacteriophage products have received full FDA approval for human clinical use. Despite this, the FDA has approved phage therapy for use in animals and plants. Phage products intended for human treatment are classified as biological products and drugs, regulated by the FDA’s Center for Biologics Evaluation and Research (CBER).
Currently, patient access to phage therapy in the U.S. is primarily through specific regulatory pathways: Investigational New Drug (IND) applications, compassionate use, and clinical trials. For patients with serious, life-threatening bacterial infections that have not responded to all available conventional treatments, physicians can apply for an Emergency or Single Patient Expanded Access IND from the FDA. This pathway allows for the use of unapproved medicines when no comparable therapies exist and the patient’s condition is severe. Approximately 99% of these emergency IND requests are approved.
Several institutions and consortia in the U.S. are actively involved in phage research and compassionate use. The Center for Innovative Phage Applications and Therapeutics (IPATH) at the University of California San Diego (UCSD) was established in 2018 as the first center of its kind in North America. IPATH supports compassionate use cases, helps identify suitable phages, and advises physicians on the IND submission process. They reported that phage therapy was safe and effective in clearing 7 out of the first 10 infections they helped treat.
Other organizations, such as Adaptive Phage Therapeutics (APT) and Intralytix, are also developing phage products and conducting clinical trials. The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), has awarded grants to institutes across the U.S. to support phage therapy research. These efforts aim to expand the understanding of phage biology, identify new therapeutic candidates, and establish the safety and efficacy of phage treatments through rigorous studies.