A deadly superbug, an untested treatment and one chance to survive
In late 2015, Strathdee, an epidemiologist, and her husband, Patterson, were in Egypt when Patterson came down with a bug. In time, it was diagnosed as a deadly, antibiotic-resistant superbug. As he lay in a California hospital bed, all options seemed to be exhausted. Strathdee, who grew up in Toronto, decided to research alternative ideas, and focused on phage therapy — a pre-antibiotic treatment that uses a virus to kill bacteria.
In most countries, phage therapy had fallen out of favour after penicillin came to market in the 1940s. Understandable, since antibiotics were true miracle drugs until antibioticresistant bacteria began to surface as a significant concern in 1959.
The alarm over a coming pandemic of deadly antibiotic- Steffanie Strathdee and Thomas Patterson in August 2016 at their home in Carlsbad, Calif., two weeks after his discharge from hospital. resistant bacteria threatening human life had been sounded the world over with no apparent effect. Outdated ideas, ignorance, and plain prejudice had hobbled the scientific and medical community. Although phages were studied extensively by basic scientists in molecular biology and genetic engineering experiments, relatively few scientists had persisted to research phage for its therapeutic potential, most of them labouring in obscurity at universities or a few small biotechs.
As much as some phage therapy proponents were eager to see it embraced as a potentially “new” way of treating antibiotic-resistant bacteria, bureaucratic hurdles and the lack of empirical data on efficacy had thwarted attempts to advance its clinical use in the Western world for more than a century, and that muddled past had muddied prospects ever since.
Phage therapy clinics in Tbilisi [Georgia] and Wrocław [Poland] advertised treatment and there were online accounts of some success stories, but few rigorous studies in humans had been published in English journals.
I could not find a single article describing phage therapy to treat humans infected with Acinetobacter baumannii. It had been done in Petri dishes. In mice. A few rats. It seemed promising, but could I really justify turning my husband into a guinea pig? If things went sideways, how would I explain my decision to inject him with a legion of viruses to his daughters?
Using viruses to chase bacteria reminded me of the children’s song about the old lady who swallows a spider to catch a fly: She swallowed the spider to catch the fly But I don’t know why she swallowed the fly —
Perhaps she’ll die.
It was after 11 p.m. and I was starting to fade, but heard a ping from Facebook messenger — my colleague Maria Ekstrand in San Francisco who knew both Tom and me well wrote to tell me about a friend of hers who had flown to Tbilisi to have her MRSA infection treated at the Eliava Phage Therapy Center. It had worked. Another cosmic coincidence? Some might call it a sign, and maybe it was, but I needed more than a sign. I needed a path forward, even if I had to build it myself.
I fired off an email to Chip [Dr. Robert “Chip” Schooley, a friend and infectiousdisease specialist] attaching a research paper on A. baumannii phages I had found by Dr. Maia Merabishvili, a phage researcher from the Eliava Center who was now based in Brussels. I could just imagine Chip’s eyebrows twitching as he read my email.
Dear Chip, I know that we are running out of options to save Tom, so I have been exploring alternatives to antibiotics. What do you think about phage therapy? I know it sounds a little woo woo, but it might be worth a shot.
If I was going to try to obtain an experimental treatment to save Tom’s life, it was going to take an act of God, a lot of luck, and more energy than I might be able to muster. But just thinking about phage therapy gave me an adrenaline surge. I’d loved my undergrad virology class years ago, and now the challenge was anything but academic.
I couldn’t help but find it profound that I had to return to my own past, my training, to bring an obscure thread of science forward to find a cure for Tom. And that the potential answer could have been there all along without me or anyone seeing it until now — I could feel the excitement building in my gut. And it wasn’t the knot of fear that I’d been learning to live with since Luxor. Could this really be it?
I checked my email again before going to bed. Chip was burning the midnight oil, too. He had already replied to my message.
It’s an incredibly interesting idea that would be worth thinking about — although it might be slightly ahead of its time … If you can find some phages with activity against Acinetobacter, I will give the FDA a call to see if they will issue an eIND [Emergency Investigational New Drug Application] for compassionate use.
Chip’s positive response should have been nothing but exciting. But at first, I could only focus on two words: “compassionate use.” I stared at those words for a full minute. So, there we had it. Even Chip was admitting now that Tom was dying.
I could just hear him reviewing Tom’s situation with Connie through his most objective lens. Chip was deeply empathetic, but he’d told me once how, as a physician, you have to compartmentalize. You can’t let yourself get so emotionally wound up that you can’t function as your patient’s physician, or it means they don’t have a physician, and that’s worse. You have to be able to make scientifically and medically sound, pragmatic decisions. And the truth was, despite everyone’s hard work and hope, there was no way you could convince yourself that Tom was getting better.
He was barely communicating. His kidneys were barely holding on. He needed pressors to maintain a livable pulse and he needed the vent to get enough oxygen. And the superbug wasn’t the only thing killing him. His underlying issues — the pancreatitis foremost — and the collateral damage meant that his body was breaking down, bit by bit. His organ systems were failing.
Our best hope now was that the FDA would decide that because he was going to die anyway, an experimental therapy was worth the risk.
It had been a long-running joke between Tom and me that wherever we travelled, Tom “collected” local parasites or weird infections, always returning home with some malady or another. Like Cameron and his Pokémon cards. Tom had even quipped once, after our MRSA [infection] experience, that it was his goal to collect all six of those deadly ESKAPE pathogens. It had seemed funny at the time: “Gotta catch ’em all!” Now his next acquisition — after Acinetobacter — could be an entirely new character from a new deck of cards, one with protective powers, maybe the ace up his sleeve.
At the hospital the next morning, I strode through the atrium feeling bathed in the light and the energy of possibility. The ride up to the TICU wasn’t the usual discouraging descent into fear. And when I reached Bed 11, I was ready for a painful but important conversation. Tom and I needed to have another “life or death” talk. The first talk we’d had like this was in the Frankfurt ICU, more than two months before — two months of this “near-death” experience. Whatever I’d said that day had triggered his fight response. Granted, today the trach vent made it a one-way conversation, but we had to do our best.
I leaned close and took his hand in mine, hating the gloves I had to wear. I thought I detected Tom’s lips move at my touch, which was a good sign. Maybe he was just conscious enough to hear me.
I told him the truth. The docs were now out of ammunition. They were all out of antibiotics, and he was not a candidate for surgery. So, if he wanted to live, he’d need to fight again. This would be a fight for time, while I looked for an alternative treatment I didn’t know if I could find. And a fight against the continuing deterioration of his body, beginning to trigger organ shutdowns. No guarantees of anything, except certain death if we both stopped trying.
“Remember we had that talk back in the Frankfurt ICU, where I told you that if you want to live, you have to fight?” I began, and my voice faltered, catching in my throat. I swallowed and tried again. “Honey, I know you have been fighting so hard, and you’re very tired. The doctors here are doing all they can, but they tell me they can’t do anything else.”
I knew that he knew this. In the still pause, I watched as a single tear welled up in the corner of his eye and spilled across his eyelashes. He blinked, but his eyes stayed closed as another tear trailed down his cheek. I let go of his hand, and wiped his face with a cloth. Later, I realized that I’d clenched my other fist when I saw that my nails had a dug four red half-crescent moons into the palm of my hand.
“I want to grow old with you, Tom. But I don’t want you to live just because I want you to. That would be too selfish. This is your life, not mine.” I took a deep breath. “And the thing is, it’s OK if you don’t want to fight anymore.”
No clear response, if I was being objective, which admittedly was getting harder. He couldn’t see me, but I was pretty sure he heard how my voice wobbled. I held his hand again gently.
“But if you want to fight, I’m going to fight, too. We’re in this together. I will leave no stone unturned. In fact, I’ve been reading some articles on experimental treatment for multi-drug-resistant infections, and I have an idea …”
I told him about the phages, how they’d evolved over millennia to become the perfect predator of their hosts — bacteria. Of course, if he were awake, he’d be chomping at the bit, asking a million questions. But I had to cover all the bases, an effort at informed consent, in case he could hear me.
So, I laid it out. Longshot as treatments go. Sound science as far as it went — but untested on humans infected with a fully antibiotic-resistant Acinetobacter baumannii strain that had totally colonized the body. Experimental, which meant it could take time to get permission to use on him. And no guarantees that it would work or, even if it did, that he’d recover from the damage already done.
“I’m not sure how to do it yet, but maybe we can get you some experimental phage therapy.” I squeezed his hand gently. “If you want to try it, can you squeeze my hand?”
He seemed to stiffen but … nothing. And then — he squeezed back, hard. No retreat.
That night, when I went to bed, even looking at the worst-case scenario with clarity, I didn’t cry myself to sleep. I dreamed of wading waist-deep in a swamp, hunting for phages as if panning for gold. The water was murky and putrid, swirling with images of alienlooking phages, their heads the shape of microscopic geodesic domes and rocket ship tails trailing long filamentous fibres. When I looked down, I saw that I wasn’t holding a miner’s pan, but the cracked bedpan from the clinic in Luxor.
I woke in a panic and rubbed my face with sweaty palms. With relief, I realized it was just a dream. But for the first time waking up to the real-life nightmare of Tom’s illness, I felt more exhilarated, less hopeless. I leapt out of bed so fast I startled Newt and the kittens, who had curled around my knees while I slept.
Now all I needed was to find some phages. How hard could that be?