The Bond That Beat the Superbug

Tom Patterson is dying. He has been for months. In and out of consciousness, wracked with pain and hallucinations, he lays confined to his hospital bed, a shadow of the man he once was.

Around him, there are more shadows in the room. He senses them, and sometimes when he opens his eyes, he can see. He sees a nurse beside him, wishing him a happy birthday. He is 69. In the background, a song plays, the Beatles’ “While My Guitar Gently Weeps.” Patterson’s wife, Steffanie, comes into focus. She’s weeping too, telling him she loves him, but that there is nothing else doctors can do. She asks if he wants to keep fighting. But Patterson cannot move or speak. He can’t give a thumbs up because he can’t find his hands.

He is filled with despair until noticing the rest of the room, the surrounding shadows becoming doctors and friends standing around him. He finds his hands. One of them is holding Steffanie’s. He squeezes. Yes, he shouts voicelessly. I want to fight. I want to live.

They had always wanted to go to Egypt. Over Thanksgiving break in 2015, Patterson, a professor in the Department of Psychiatry at UC San Diego School of Medicine, and his wife, Steffanie Strathdee, associate dean of Global Health Sciences and Harold Simon Professor of Global Health, set out to cross another item off their bucket list. 

When they returned to San Diego many weeks later, Patterson would be deathly ill. He would soon slip into a coma, plagued by hallucinations, intense pain and something worse: a multidrug resistant strain of a bacterium called Acinetobacter baumannii, an opportunistic and often deadly pathogen widely known as one of the world’s most dangerous superbugs. Indeed, Patterson’s infection would defy doctors in three countries and virtually every modern antibiotic.

“That’s a period of my life I don’t remember,” he says. “There was so much pain that it’s almost beyond your ability to cope. I’m happy to not remember.”

He was able to fight back, nonetheless, thanks to the extraordinary efforts of his wife, his doctor and a network of colleagues and staff at UC San Diego Health. The effort was compounded by researchers across the country and world, many of them strangers yet rallying to help save his life using an experimental, last-ditch therapy based upon bacteria-eating viruses called bacteriophages.

The word bacteriophage derives from Greek for “bacteria eater.” As ubiquitous as they are ancient, phages outnumber every other form of life on the planet. They exist anywhere bacteria exist—on land, sea and air, on your skin and inside your gut where, says Robert “Chip” Schooley, MD, chief of the Division of Infectious Disease at UC San Diego School of Medicine and the head of Patterson’s medical team, they perform a “recurring Darwinian dance” with bacteria.

In the early 1900s, phages promised to be a new kind of anti-bacterial therapy. But they are finicky eaters and difficult to work with. Each strain of virus targets only a particular bacterium, with both predator and prey constantly evolving new tools of attack and defense. Phage therapy fell out of favor in the United States and most of Europe with the advent of antibiotics, the presumed wonder drugs. Only in places like Russia and Poland did significant phage research continue, though it was largely ignored until recent rising global antimicrobial resistance rendered the wonder drugs much less wondrous. 

On vacation in Egypt, Patterson and Strathdee are thoroughly enjoying their first few days abroad. They see the main sights yet also make a point to go off the beaten path. They visit the tourist areas in Luxor; Patterson crawls into the dark bowels of the Red Pyramid near Cairo. A few days later, on a Nile River cruise ship, he becomes violently and persistently ill. At first, Steffanie thinks food poisoning. They are referred to a local clinic for treatment. Tom’s condition worsens. Steffanie calls Schooley back at UC San Diego. They suspect pancreatitis, an inflammation of the pancreas. Egyptian doctors agree. Patterson is given antibiotics and, occasionally, pain medication for his now-ceaseless agony. He drifts in and out of consciousness, and the hallucinations start. He is sicker than ever.

They decide to try phage therapy, but they will need help. With an estimated ten million trillion trillion (1031) bacteriophages in the world, finding the right strain is looking for a needle in a trillion haystacks. They find a scientific community at the ready—all across the country, in people and places they do not always know. Ultimately, their phage hunt results in three partners with phages deemed active against Patterson’s bacterial infection: the U.S. Navy’s Biological Defense Research Directorate in Frederick, Md.; the Center for Phage Technology at Texas A&M University; and AmpliPhi, a San Diego-based biotech company specializing in bacteriophage-based therapies. 

Some of the phages, remarkably, are derived from sewage. When samples arrive, the team partners with microbial ecologists at San Diego State University to purify them for clinical use. Many phage strains are combined in “cocktails” to confound bacterial resistance.

There is a sense of urgency. In an unprecedented matter of days, the Food and Drug Administration grants Schooley emergency approval to use the phages. Strathdee’s hand shakes as she signs the release forms. Everyone understands this may be Patterson’s last chance.

But it may also be a first. As far as UC San Diego researchers and doctors know, what they plan to do has never been done before. In most cases, phages are administered orally or topically to treat localized infections. But Patterson’s entire body has been colonized by A. baumannii, so phages must be introduced through catheters directly into his abdominal cavity and infused intravenously throughout his body. “That makes them more effective,” says Schooley. “The action is at the interface of the patient and the organism.”

No one can predict what will happen. Phage therapy is unproven and experimental. It could kill rather than cure. Schooley says the UC San Diego Health medical team is learning on the fly, adjusting treatment based upon Patterson’s response, which ultimately proves remarkable. Within three days of the start of IV therapy, Patterson emerges from his coma. Within a week, he no longer needs life support.

Subsequent treatment, however, will not be easy. The learning curve is steep and unmarked. Inside Patterson, bacteria and phages do their Darwinian dance. The bacteria develop resistance, but Navy scientists create a new phage cocktail in a remarkable three days. It’s a long dance. There are good days and bad. There are setbacks, including recurrent bouts of life-threatening sepsis. Patterson will lose more than 100 pounds during his hospitalization and require intense rehabilitation.

But dark thoughts of Tom dying pass away. One month after therapy began, his immune system is strong enough to fight the superbug on its own and phage treatment is discontinued. By June, the bug is gone from his body.
In mid-August 2016, more than nine months after he first fell ill, Patterson is discharged from the hospital and goes home. There will be more months of rehab, both physical and mental. Patterson says even when he was comatose, he could hear and recognize voices and realize that beyond the darkness, there was life and hope. But recovery is long and arduous. There are moments when he says it feels like his brain is coming alive one neuron at a time, firing like a string of firecrackers.

In the backyard of their Carlsbad home, swathed in the golden glow of an afternoon sun, Patterson and Strathdee ponder their good fortune. His fate could have been different, but he is married to a trained scientist who was determined to find a remedy—and they both work at UC San Diego School of Medicine. “Tom was fortunate to be in a place that had all of the resources and courage necessary to support him while this innovative therapy was developed,” says Schooley. “I think a lot of other places would have hesitated. It speaks to the strength of a multidimensional medical center and critical components like the ICU physicians and nurses, pharmacy, interventional radiology and others.”

Schooley believes Tom’s case can help advance interest and development of phage therapy. Indeed, the U.S. Navy is collaborating with Schooley and UC San Diego to create a Phage Therapy Center.

Patterson is philosophical. “In a sense, our lives collided with the evolution of phage therapy,” he says. “What the field needed was someone who was dying, a wife like Steff who was willing to try it as a desperate measure, a network of researchers who were willing to undertake a phage hunt, a university hospital system willing to make it happen and a dedicated doctor who put his reputation on the line to try something completely out of the box. We got all this—and in record time.”

Like Patterson’s case, phage research will likely be bumpy and unpredictable. Phages seem safe, but before they can be used as a standard of care, daunting regulatory and technical hurdles loom. “The FDA is used to saying, ‘This is an antibiotic. We know what the structure is and you’re giving this antibiotic to multiple people,’” says Schooley. “With bacteriophage therapy, we are dealing with an approach that requires a specific cocktail for each patient. It is the ultimate personalized medicine.”

In other words, every treatment will be a clinical trial of one. Each patient will represent success or failure. Not surprisingly, Patterson leans toward the former. He believes his experience can be translated into new treatments for others, perhaps many others. In fact, there have been subsequent phage treatments in the U.S. based on the lessons learned in Patterson’s case.

“Phage therapy has really been a miracle for me, and I’m excited for what it might mean to millions of people who may be cured from multidrug-resistant infections in the future,” Patterson says. “Call it bizarre, but I feel somewhat privileged to have experienced all of this and still be alive and hopefully make a change. To think that someone else could benefit from my experience—that it might generate interest, and perhaps create a whole new wave of treatment for something that’s a growing problem.”

“To have taken something so trauma tic and turned it into something good,” says Strathdee, “it gives you a sense of power and fierceness. Like, we can do anything now. Bring it on.”