So they said. They were wrong.
More than 150 antibiotics have been developed since the discovery of penicillin, and for the majority of antibiotics available, resistance has emerged and gone global. At the rate that scientists now know that bacteria develop resistance, researchers would need to create about thirty-five new classes of antibiotics each century to stay ahead of bacterial pathogens. Instead, no new antibiotic drug class has entered the market since 1980, and no new class of antibiotics has been discovered to treat Gram-negative bacteria like A. baumannii since 1962, before I was born. All bacteria have an inner cell membrane, but one reason that Gram-negatives tend to be more resistant to antibiotics is that they have a hardy outer membrane as well, which makes it tough for many antibiotics to penetrate. In 2015, there was only one novel drug in clinical development that could potentially fight Gram-negative bacteria.
These days, most Big Pharma companies have shut down their antibiotic research labs or laid off researchers. It’s much easier (and cheaper) to develop new versions of drugs within known antibiotic classes than to push for brand-new ones. The once massive engines of government funding and private profit that powered new drug development in the mid-twentieth century can now barely keep the lights on. Global health experts have long called for antibiotic stewardship, which includes using antibiotics sparingly and saving some as a last resort. But this only created even more of a disincentive for the pharma industry. One expert compared pharma’s reticence for investing in new antibiotics to the public’s disinclination to buy fire extinguishers. Why pay so much money for something you might never use?
Bacteria, meanwhile, have continued to evolve rapidly. As bacteria have grown more resistant, the antibiotics we’ve relied on to treat Salmonella, Campylobacter, E. coli, and other relatively common foodborne pathogens have become less effective. The CDC estimates that one in five antibiotic-resistant infections in humans originate from food and animals. That’s because in many countries, animals aren’t just given antibiotics to treat and prevent disease, but to make them grow fatter, faster. But despite a boatload of studies, the agriculture and pharma industries have maintained that the link between antibiotics fed to livestock and antibiotic resistance in humans hasn’t been unequivocally proven. In 2018, a study that involved a “molecular clock” analysis would firmly establish that specific antibiotic-resistant genes from E. coli cultured from chicken in Arizona farms were precisely the same ones found in supermarket poultry and, subsequently, in hospitalized patients with serious urinary tract infections.
In hospitals, where patients are particularly vulnerable to acquiring antibiotic-resistant bacteria, containment is critical, but conventional infection control protocols fall short of superbugs’ capacity to hide, proliferate, and mutate even under watchful eyes. In one study, a team of researchers collected bacterial cultures from fomites, surfaces and objects that can spread pathogens, including bed rails, countertops, faucet handles, and computer mice in occupied patient hospital rooms. They also swabbed the hands and noses of patients and staff, along with the shoes, shirts, and cell phones of staff members. Over the course of a patient’s hospital stay, patients’ skin and room surfaces became “microbially similar”—meaning the bacteria comingled, cross-contaminating the environment and everything and everyone in it. Based on other reports, the stats are startling: in a three-hundred-bed hospital, there may be up to 64 million possible microbial transfers. Other studies confirm that our surroundings contribute to the makeup of our own microbial communities, and vice versa. Surprisingly, this can include the antiseptics commonly used to scour hospitals and to clean healthcare workers’ hands, and chemicals used in antibacterial products such as paints and scrubs, some of which actually promote the growth of drug-resistant bacterial strains as they kill off the vulnerable germs and make way for superbugs to flourish. One study even found that bathroom hand dryers can spread antibiotic-resistant bacteria to neighboring surfaces.
Points of transmission also include so-called structural factors, from sophisticated medical devices to IVs and other tubing, which create the equivalent of mass transit for microbes. The year Tom fell ill, a major medical news story would report the discovery that lens maker Olympus, which manufactures medical equipment, knew that its endoscopes could not be adequately disinfected. After several global outbreaks that killed people receiving regular procedures like colonoscopies, the source was traced back to superbugs that hid inside Olympus endoscopes. In Tom’s case, some of his doctors speculated that the source of his A. baumannii infection was the nasogastric tube inserted in the Luxor clinic to siphon the bile from his stomach to reduce vomiting. We’ll never know.
It’s no joke that hospitals are now often referred to as the worst place to get well. Superbugs are looking out the hospital windows, licking their chops at the feast that awaits them in this era of superbugs without borders.
Tom: Interlude III
Steff and I are walking in the desert. Not a single living thing is within sight. All I can see for miles is sand, hued a deep red, billowing all around us. The sand stings our eyes and the wind chafes our skin. There is no sun in the sky, but the heat is blazing. We walk in silence, saving our energy. I am so thirsty, but there is no water. My sweat and saliva evaporate into the air with a sizzle. We will die out here, I think.
A Bedouin man suddenly appears as if rising from the dune, directly in front of us. He is dressed in a white flowing robe, and his head is wrapped in a turban. I sense he is a holy man. He walks toward us, carrying a package that he is careful not to drop. He stops in front of us, and deftly unravels ribbons of brown cloth from the package. His skin is tan and supple; his fingernails are buffed oval moons. We eye his package hungrily, like animals. I am hoping it is water, or food. Steff looks at me, thinking the same thing. We know we are not supposed to speak. The man looks up at us. His eyes are black pebbles, recessed deep inside his skull. It is impossible to tell how old he is; his skin is unlined, although his beard is long and white.
The man presents each of us with the contents of the package, which are two small wooden boxes that fit neatly into the palm of our hands. Each box is intricately carved with our names in hieroglyphics. Steff and I open our boxes simultaneously. Inside mine is a tiny green leaf, identical to Steff’s. The leaf is plump and waxy and reminds me of a fig leaf.
“Eat,” the man says to us. Steff and I look at each other and then at the holy man. Surely he is not serious. How can a single leaf, one so impossibly small, nourish us in a desert, where there is no water? Steff does not hesitate. She picks up her leaf, and gobbles it up. I cannot. My mouth is too parched. I am too tired. I wait.
The man is gone. Vanished. As if he were a mirage. Maybe he is. We walk more, for days, months. Our feet sink deep into the red sand. Each step is more difficult for me, but Steff is walking faster. She is impatient, waiting for me, but she does not say this. The holy man reappears, as if rising from the heat waves, with outstretched hands. He points to Steff. “My child, you have eaten, so you may leave.”
Steff does not look back at me; she just drifts away. I see her figure getting smaller and smaller, until she disappears. Now I am alone with the holy man. I am filled with dread.
“You have one day left to eat, or you will remain in the desert for one hundred years,” he says solemnly, shaking his head.
I look down at the box in my hand and lift open its lid again. The leaf is even smaller now, shriveled and dry. I pick the leaf up carefully by the stem, but it flakes into tiny fragments. Some blow away in a gust of wind. I only succeed in eating a small piece that remains attached to the stem. I want to cry in despair, but I have no tears left. I want to ask the holy man for water, but he has evaporated. I am overcome with a profound sense of loneliness.
My palm, holding the empty box, is like an alluvial plain. Erosion has weathered my skin, which flakes off like white, scaly scabs, revealing deep red rivulets that carry my blood. The ridges and furrows of my fingers
and thumbs are now devoid of whorls, a dermatoglyphic aberration that means I am no longer a person. I am a cadaver. The skin on my feet peels off like snakeskin and falls down, to what I recognize suddenly is the TICU floor. A woman sweeps up my skin with a broom. I am so worthless that my body is being disposed of. I am disappearing cell by cell into a red bin that is labeled with the word BIOHAZARD. I open my mouth to scream, but no sound comes out.
I know that this is how I will die.
12
THE ALTERNATE REALITY CLUB
December 24, 2015—January 16, 2016
In no time, Christmas was upon us. The girls flew down from the Bay Area to be with Tom and spent most of the holidays shuttling between our house and the hospital. In normal times, they’d always loved hanging out and watching TV together on visits, when they weren’t swimming in the ocean, that is. Now all the action was on the flat screen, but Tom’s sagging spirits were buoyed by their presence. And it meant I could spend a few days in Vancouver with Cameron, who was about to turn twenty-three. He’d been born on Christmas Eve, so his birthday had always had the happy holiday aspect to it. As a child, Cam had preferred low-key birthdays at home with his dad and me. He was hell-bent on collecting all available Pokémon trading cards and memorized each form they evolved into. He also played Pokémon on his Gameboy, pitting them against each other and watching them obtain new superpowers after their successive battles. At the time, the Pokémon theme song drove me and other parents insane: “Gotta catch ’em all, gotta catch ’em all!”
For a kid who just didn’t “get” other kids (and they didn’t get him), he’d been pleasantly surprised at university, where he finally made some great friends. Every year around Christmas, I’d treat Cameron and his buddies to a big holiday dinner that served as a birthday party. He’d met these friends in the campus Alternate Reality Club, and at least this year, it seemed a fitting name for all of us. Only their version was an upbeat take on life; ours was no fun.
Another of Cameron’s early obsessions was building Star Wars Lego action figures, which I delighted in, since he and I were both big fans. One day, when he just three, and his dad, Steve, was serving him dinner, I’d reminded him to use his fork. He’d looked skyward, grabbed his fork in his fist and cried, “Use the fork, Luke!” We all burst out laughing—what I wouldn’t do for some help channeling the Force from Obi-Wan Kenobi right now.
We had a long tradition now of going to the Star Wars premieres together right before Christmas. Months ago, I’d pre-purchased seats for Cameron, me, and Tom to go see Star Wars: The Force Awakens. It was the first Star Wars movie in years, and Cam and I had been counting the days. Obviously, Tom wasn’t going to make the movie this year, so Cam brought along his friend Jesse instead. The movie was fantastic, but I couldn’t help but compare the fights between the Jedi and the First Order to the one going on in the TICU between the A. baumannii bacteria and Tom’s immune system. Could Tom’s antibodies and natural killer cells annihilate the bacteria? I remembered Chip’s PowerPoint that he’d sent me in Frankfurt pinpointing the anatomical ampulla of Vater—the very junction where that gallstone had been unable to pass and where the whole damn pseudocyst had started to form like the Death Star. Could we find some kind of biological blaster to zap Tom’s A. baumannii?
I was already showing signs of PTSD and didn’t know it at the time. Every time one of the X-wing pilots blew up a ship, the thundering Dolby surround sound from the movie theater pounded inside my head. My nerves felt ragged and jangled; every suspenseful scene triggered an exaggerated sense of shock. I looked sideways to Cameron and Jesse to see if they were reacting the same way. Both were sitting back, eating popcorn and grinning, taking it in like a scene in a movie. Because it was a movie. But for me, my world was shattering. Part of me was in the movie, and another part of me was watching the other me and Tom getting blown to bits. Afterward, Cameron could see I was shell-shocked.
“Mom,” he confided, “maybe you should just go back to watching Forensic Files until Tom gets out of the hospital.”
I’d been a longtime fan of this corny TV docudrama that we all loved and loathed. Lately, I’d taken to binge-watching it like a zombie, occupying some nail-biter region of my brain while the calm, analytical part continued to work on the puzzle of saving Tom’s life, which was like a special edition of a Rubik’s Cube. The show was a dramatization of true crimes that were neatly solved with the help of forensic science, all within the program’s allotted twenty-four minutes. Somehow, the answer was always right in front of their eyes; they just had to use cutting-edge science and technology to see it. In Tom’s case, the solutions seemed to come and go: now you see it, now you don’t.
Cameron was no blind optimist by nature. His brain, like mine, was hardwired for unsentimental logic and reason. But compassionate qualities had emerged in different ways in recent years, especially with the death of his father several years earlier, and now through this family crisis. Over a beer before I left to fly back to San Diego, he toasted me, telling me that he was very proud that I saved Tom’s life. I was deeply moved. Whether it was true or not seemed to change hour by hour.
Tom’s clinical status seemed to be oddly in limbo. Although his A. baumannii was now resistant to each of the antibiotics that had once looked promising, as long as the bacteria remained contained in the pseudocyst, something appeared to be slowing the bacteria’s voracious growth just slightly. It might have been his own immune system, which seemed to rally sporadically.
By New Year’s Eve, the mood at home was lifting as Tom continued to make small gains. I could hardly wait to usher in 2016. I wanted 2015 behind us so badly. It seemed like magical thinking to imagine that we could just turn the page. But on the plus side, his condition was now officially listed as “stable”—something that just a few weeks ago we never thought we’d see. And he’d been assigned to the more general hospitalist team to oversee his care, rather than the pulmonary and critical care team. The fact that he was shedding specialists was a good sign. And on New Year’s Day, something remarkable happened: Tom was moved from the TICU to a regular ward. The girls and I were ecstatic. Contact precautions were still enforced, but now he would be able to get more sleep and regular physical therapy. The page had turned.
At home, I adopted two new kittens to join stodgy Newt as the welcoming committee for Tom’s return home, which I was hoping would be any day now. Bonita and Paradita were both strays from Animal Rescuers without Borders. I took a little video of them chowing down at the same feeding bowl one afternoon and showed it to Tom. He was amused, but it made him even more homesick. As New Year’s resolutions go, getting Tom home was the one we all shared. But with every new complication and obstacle, we were forced to reconfigure expectations and then renew that resolve. And wait.
One day in early January, Davey met me for lunch after we visited Tom together. He wanted to fill me in on the results just in from the antibiotic synergy testing that the lab had run. After all this waiting, the findings were a major disappointment. The tests had turned up no new antibiotic approaches—no combination had an effect. Tom was holding on, stable, but we were running out of options to kill the A. baumannii. Over a burger, Davey happened to mention a publication he had read by one of our colleague’s research labs. It reported that a combination of three antibiotics—rifampin, azithromycin, and colistin—is synergistic against some multi-drug-resistant bacteria, at least in the lab. Normally, no one would use azithromycin to treat a Gram-negative bacterial infection, but the team’s research suggested that the azithromycin weakened the bacterial cell wall, which allowed the colistin to get inside, where it could kill it. I was intrigued. That night, I did a PubMed search, found the paper, and read it myself.
A year ago, a study like this about mix-and-match antibiotics would have made for interesting conversation—the kind you discuss at a brown-bag seminar watching colleagues’ projects in fascinating areas far removed from your own work. Now, after taking a leave o
f absence from my usual work because keeping Tom alive consumed me, even a single study that suggested an alternate route out of this dead end was worth tracking down. Could we try this approach on Tom?
There was only one way to find out.
I’d crossed paths with the senior author, Dr. Victor Nizet, at university meetings, and I didn’t hesitate to drop him an email now. Would he be willing to test his drug combination against Tom’s bacterial isolate? He agreed, and suggested that they first run some tests in the lab to see if the synergy was observed on Tom’s superbug. Within a few days, Dr. Monika Kumaraswamy, an infectious disease fellow from Victor’s lab, showed that the combination had some benefit, but that was in a Petri dish. Still, it was something.
The next day, I asked Tom if he would be willing to try this new experimental antibiotic combination if the docs okayed it. He was on board. Next, I emailed Chip to see if the rest of the infectious disease team gave the thumbs-up. Chip agreed, pointing out, as Davey had, that there was little harm in adding azithromycin to Tom’s regimen because it was a much safer antibiotic than the others he was already on.
On this new antibiotic cocktail, Tom started to improve marginally over the following week. He slept, started to eat soft food, and even kept some of it down. He worked with Amy, the physical therapist, twice a day, learning to sit up and then stand. Victor’s antibiotic combo was not a cure, but by holding the infection at bay, it bought us more time.
Chip was encouraged.
The Perfect Predator Page 11