He Almost Died from a Deadly Superbug. A Virus Saved Him.
An attacking rogue hippo, giant jumping spiders, even a coup in Timbuktu couldn't knock out Tom Patterson, but now he was losing the fight against a microscopic bacteria.
Death seemed inevitable, perhaps hours away, despite heroic efforts to keep him alive.
It was the deadly drug-resistant superbug Acinetobacter baumannii. The infection struck during a holiday trip with his wife to the pyramids in Egypt and had sent his body into toxic shock. His health was deteriorating so rapidly that his insurance company paid to medevac him first to Germany, then home to San Diego.
Weeks passed as he lay in a coma, shedding more than a hundred pounds. Several major organs were on the precipice of collapse, and death seemed inevitable, perhaps hours away despite heroic efforts by a major research university hospital to keep Tom alive.
Tom Patterson in a deep coma on March 14, 2016, the day before phage therapy was initiated.
(Courtesy Steffanie Strathdee)
Then doctors tried something boldly experimental -- injecting him with a cocktail of bacteriophages, tiny viruses that might infect and kill the bacteria ravaging his body.
It worked. Days later Tom's eyes fluttered open for a few brief seconds, signaling that the corner had been turned. Recovery would take more weeks in the hospital and about a year of rehabilitation before life began to resemble anything near normal.
In her new book The Perfect Predator, Tom's wife, Steffanie Strathdee, recounts the personal and scientific ordeal from twin perspectives as not only his spouse but also as a research epidemiologist who has traveled the world to track down diseases.
Part of the reason why Steff wrote the book is that both she and Tom suffered severe PTSD after his illness. She says they also felt it was "part of our mission, to ensure that phage therapy wasn't going to be forgotten for another hundred years."
Tom Patterson and Steffanie Strathdee taking a first breath of fresh air during recovery outside the UCSD hospital.
(Courtesy Steffanie Strathdee)
From Prehistoric Arms Race to Medical Marvel
Bacteriophages, or phages for short, evolved as part of the natural ecosystem. They are viruses that infect bacteria, hijacking their host's cellular mechanisms to reproduce themselves, and in the process destroying the bacteria. The entire cycle plays out in about 20-60 minutes, explains Ben Chan, a phage research scientist at Yale University.
They were first used to treat bacterial infections a century ago. But the development of antibiotics soon eclipsed their use as medicine and a combination of scientific, economic, and political factors relegated them to a dusty corner of science. The emergence of multidrug-resistant bacteria has highlighted the limitations of antibiotics and prompted a search for new approaches, including a revived interest in phages.
Most phages are very picky, seeking out not just a specific type of bacteria, but often a specific strain within a family of bacteria. They also prefer to infect healthy replicating bacteria, not those that are at rest. That's what makes them so intriguing to tap as potential therapy.
Tom's case was one of the first times that phages were successfully infused into the bloodstream of a human.
Phages and bacteria evolved measures and countermeasures to each other in an "arms race" that began near the dawn of life on the planet. It is not that one consciously tries to thwart the other, says Chan, it's that countless variations of each exists in the world and when a phage gains the upper hand and kills off susceptible bacteria, it opens up a space in the ecosystem for similar bacteria that are not vulnerable to the phage to increase in numbers. Then a new phage variant comes along and the cycle repeats.
Robert "Chip" Schooley is head of infectious diseases at the University of California San Diego (UCSD) School of Medicine and a leading expert on treating HIV. He had no background with phages but when Steff, a friend and colleague, approached him in desperation about using them with Tom, he sprang into action to learn all he could, and to create a network of experts who might provide phages capable of killing Acinetobacter.
"There is very little evidence that phage[s] are dangerous," Chip concluded after first reviewing the literature and now after a few years of experience using them. He compares broad-spectrum antibiotics to using a bazooka, where every time you use them, less and less of the "good" bacteria in the body are left. "With a phage cocktail what you're really doing is more of a laser."
Collaborating labs were able to identify two sets of phage cocktails that were sensitive to Tom's particular bacterial infection. And the FDA acted with lightning speed to authorize the experimental treatment.
A bag of a four-phage "cocktail" before being infused into Tom Patterson.
(Courtesy Steffanie Strathdee)
Tom's case was scientifically important because it was one of the first times that phages were successfully infused into the bloodstream of a human. Most prior use of phages involved swallowing them or placing them directly on the area of infection.
The success has since sparked a renewed interest in phages and a reexamination of their possible role in medicine.
Over the two years since Tom awoke from his coma, several other people around the world have been successfully treated with phages as part of their regimen, after antibiotics have failed.
The Future of Phage Therapy
The experience treating Tom prompted UCSD to create the Center for Innovative Phage Applications and Therapeutics (IPATH), with Chip and Steff as co-directors. Previous labs have engaged in basic research on phages, but this is the first clinical center in North America to focus on translating that knowledge into treating patients.
In January, IPATH announced the first phase 2 clinical trial approved by the FDA that will use phages intravenously. The viruses are being developed by AmpliPhi Biosciences, a San Diego-based company that supplied one of the phages used to treat Tom. The new study takes on drug resistant Staph aureus bacteria. Experimental phage therapy treatment using the company's product candidates was recently completed in 21 patients at seven hospitals who had been suffering from serious infections that did not respond to antibiotics. The reported success rate was 84 percent.
The new era of phage research is applying cutting-edge biologic and informatics tools to better understand and reshape the viruses to better attack bacteria, evade resistance, and perhaps broaden their reach a bit within a bacterial family.
Genetic engineering tools are being used to enhance the phages' ability to infect targeted bacteria.
"As we learn more and more about which biological activities are critical and in which clinical settings, there are going to be ways to optimize these activities," says Chip. Sometimes phages may be used alone, other times in combination with antibiotics.
Genetic engineering using tools are being used to enhance the phages' ability to infect targeted bacteria and better counter evolving forms of bacterial resistance in the ongoing "arms race" between the two. It isn't just theory. A patient recently was successfully treated with a genetically modified phage as part of the regimen, and the paper is in press.
In reality, given the trillions of phages in the world and the endless encounters they have had with bacteria over the millennia, it is likely that the exact phages needed to kill off certain bacteria already exist in nature. Using CRISPR to modify a phage is simply a quick way to identify the right phage useful for a given patient and produce it in the necessary quantities, rather than go search for the proverbial phage needle in a sewage haystack, says Chan.
One non-medical reason why using modified phages could be significant is that it creates an intellectual property stake, something that is patentable with a period of exclusive use. Major pharmaceutical companies and venture capitalists have been hesitant to invest in organisms found in nature; but a patentable modification may be enough to draw their interest to phage development and provide the funding for large-scale clinical trials necessary for FDA approval and broader use.
"There are 10 million trillion trillion phages on the planet, 10 to the power of 31. And the fact is that this ongoing evolutionary arms race between bacteria and phage, they've been at it for a millennia," says Steff. "We just need to exploit it."
When a patient is diagnosed with early-stage breast cancer, having surgery to remove the tumor is considered the standard of care. But what happens when a patient can’t have surgery?
Whether it’s due to high blood pressure, advanced age, heart issues, or other reasons, some breast cancer patients don’t qualify for a lumpectomy—one of the most common treatment options for early-stage breast cancer. A lumpectomy surgically removes the tumor while keeping the patient’s breast intact, while a mastectomy removes the entire breast and nearby lymph nodes.
Fortunately, a new technique called cryoablation is now available for breast cancer patients who either aren’t candidates for surgery or don’t feel comfortable undergoing a surgical procedure. With cryoablation, doctors use an ultrasound or CT scan to locate any tumors inside the patient’s breast. They then insert small, needle-like probes into the patient's breast which create an “ice ball” that surrounds the tumor and kills the cancer cells.
Cryoablation has been used for decades to treat cancers of the kidneys and liver—but only in the past few years have doctors been able to use the procedure to treat breast cancer patients. And while clinical trials have shown that cryoablation works for tumors smaller than 1.5 centimeters, a recent clinical trial at Memorial Sloan Kettering Cancer Center in New York has shown that it can work for larger tumors, too.
In this study, doctors performed cryoablation on patients whose tumors were, on average, 2.5 centimeters. The cryoablation procedure lasted for about 30 minutes, and patients were able to go home on the same day following treatment. Doctors then followed up with the patients after 16 months. In the follow-up, doctors found the recurrence rate for tumors after using cryoablation was only 10 percent.
For patients who don’t qualify for surgery, radiation and hormonal therapy is typically used to treat tumors. However, said Yolanda Brice, M.D., an interventional radiologist at Memorial Sloan Kettering Cancer Center, “when treated with only radiation and hormonal therapy, the tumors will eventually return.” Cryotherapy, Brice said, could be a more effective way to treat cancer for patients who can’t have surgery.
“The fact that we only saw a 10 percent recurrence rate in our study is incredibly promising,” she said.
Few things are more painful than a urinary tract infection (UTI). Common in men and women, these infections account for more than 8 million trips to the doctor each year and can cause an array of uncomfortable symptoms, from a burning feeling during urination to fever, vomiting, and chills. For an unlucky few, UTIs can be chronic—meaning that, despite treatment, they just keep coming back.
But new research, presented at the European Association of Urology (EAU) Congress in Paris this week, brings some hope to people who suffer from UTIs.
Clinicians from the Royal Berkshire Hospital presented the results of a long-term, nine-year clinical trial where 89 men and women who suffered from recurrent UTIs were given an oral vaccine called MV140, designed to prevent the infections. Every day for three months, the participants were given two sprays of the vaccine (flavored to taste like pineapple) and then followed over the course of nine years. Clinicians analyzed medical records and asked the study participants about symptoms to check whether any experienced UTIs or had any adverse reactions from taking the vaccine.
The results showed that across nine years, 48 of the participants (about 54%) remained completely infection-free. On average, the study participants remained infection free for 54.7 months—four and a half years.
“While we need to be pragmatic, this vaccine is a potential breakthrough in preventing UTIs and could offer a safe and effective alternative to conventional treatments,” said Gernot Bonita, Professor of Urology at the Alta Bro Medical Centre for Urology in Switzerland, who is also the EAU Chairman of Guidelines on Urological Infections.
The news comes as a relief not only for people who suffer chronic UTIs, but also to doctors who have seen an uptick in antibiotic-resistant UTIs in the past several years. Because UTIs usually require antibiotics, patients run the risk of developing a resistance to the antibiotics, making infections more difficult to treat. A preventative vaccine could mean less infections, less antibiotics, and less drug resistance overall.
“Many of our participants told us that having the vaccine restored their quality of life,” said Dr. Bob Yang, Consultant Urologist at the Royal Berkshire NHS Foundation Trust, who helped lead the research. “While we’re yet to look at the effect of this vaccine in different patient groups, this follow-up data suggests it could be a game-changer for UTI prevention if it’s offered widely, reducing the need for antibiotic treatments.”