Phage Therapy: A Promising Solution to Antibiotic Resistance
Cynthia Horton’s battle with ear infections is nothing short of a nightmare. The excruciating pain she experiences is comparable to having a root canal without anesthesia. Even worse, her ear often oozes blood and becomes infected, leaving her in constant agony. Horton’s immune system was already weakened by a lifelong struggle with lupus, and rounds of radiation and chemotherapy after a cancerous tumor surgery in 2003 further devastated her immune system. Over the years, the bacteria in her ear became resistant to antibiotics, leaving her with little to no relief.
The rise of antibiotic-resistant bacteria, or superbugs, is a pressing global health issue. These multi-drug-resistant superbugs can cause chronic infections that last for months, years, or even decades. According to Dwayne Roach, an assistant professor of bacteriophages, infectious disease, and immunology at San Diego State University, some of these bacteria become incredibly virulent over time. In the United States alone, more than 2.8 million antimicrobial-resistant infections occur each year, leading to the deaths of 5 million people worldwide.
In the search for a solution to Horton’s recurrent ear infections, doctors turned to phage therapy. Phages are tiny viruses that act as nature’s oldest predators, designed to find, attack, and devour bacteria. These microscopic creatures have already saved the lives of patients dying from superbug infections and are now being used in clinical trials as a potential solution to antibiotic resistance.
Horton’s infection was treated with phages, and scientists at the Center for Innovative Phage Applications and Therapeutics (IPATH) at UC San Diego School of Medicine discovered something unexpected. The bacteria cultured from Horton’s ear were a perfect match to a rare superbug found in certain brands of over-the-counter eye drops that were causing severe eye infections and even vision loss. This revelation opened up new possibilities for treating the eye infections using phages.
The outbreak of antibiotic-resistant eye infections began in May 2022 and quickly spread to 18 states by May 2023. Four people died, four lost their eyes, and 14 suffered vision loss. The CDC struggled to solve the outbreak because only a fraction of patients had eye infections. Some patients developed infections in other parts of their bodies, even months after they stopped using the eye drops. The culprit was a rare strain of drug-resistant Pseudomonas aeruginosa, previously unidentified in the United States.
Using the bacteria cultured from Horton’s ear and other samples sent by the CDC, scientists at IPATH identified more than a dozen phages that successfully attacked the deadly pathogen. The CDC was intrigued by this discovery and mentioned the availability of phage treatment for the superbug on its website. This raised the question of whether alternative therapies like phage treatment should be considered during outbreaks caused by bacteria with limited treatment options.
Phages are genetically programmed to search for and destroy specific types of pathogens. Bacteria employ various evasive maneuvers to counter phage attacks, but shedding their outer skins can make them vulnerable to antibiotics once again. However, the phage is neutralized in the process. To maximize success, specialists search for a variety of phages to tackle superbugs, sometimes creating a cocktail of microscopic warriors.
Phage therapy has already proven successful in treating life-threatening infections. In 2016, Steffanie Strathdee’s husband, Tom Patterson, was close to death due to an infection with a drug-resistant bacterium found in Iraq. Strathdee overcame incredible obstacles to find and deliver several cocktails of purified phages to Patterson’s doctors. One of these cocktails scared the bacteria so much that it dropped its outer capsule, allowing antibiotics to work again. Patterson made a miraculous recovery.
Phage scientists are now taking research and discovery to the next level, known as “phage 3.0.” They are mapping which phages and antibiotics work best together in the fight against pathogens. They are also investigating the body’s immune response to phages and developing new phage purification techniques for intravenous use. Clinical trials are currently underway to test the effectiveness of phages against various infections, including urinary tract infections, chronic constipation, joint infections, diabetic foot ulcers, and cystic fibrosis-related infections.
Researchers are developing libraries of phages, stockpiled with strains found in nature that are effective against specific pathogens. In Texas, a new facility is creating phages in real-time using a bioreactor, speeding up evolution to train phages to attack drug-resistant bacteria. Recent studies have shown promising results, with antibiotic-resistant bacteria eradicated in some patients and improvements seen in others.
Phage therapy holds great potential in the battle against antibiotic resistance. However, there are still many questions to be answered. Should phages be engineered or used in a cocktail? How should they be administered? These are just some of the challenges that researchers are working to overcome
