It wasn’t that I thought I was indispensable. It was that staying focused on the detail kept me from focusing on the larger, scarier picture. I’d learned my lesson in Frankfurt, where being passive and overwhelmed had added another level of crazy to a situation that was already surreal. Now, I never sat still, never just killed time. If I did, the reality of possibly losing Tom would penetrate my brain, and I didn’t want to—couldn’t—face it. The closer Tom got to death in the TICU, the more I buzzed around in the hive, looking for things I could do to help. Anything. Mostly, I learned to do tasks that the nurses’ aides did. How to brush his teeth with the little sticks that had square sponges on the end—lollypops. How to adjust the ventilator hose so it wouldn’t make that infuriating dripping sound. How to read the lines on the cardiac monitor that measured oxygen, heart rate, blood pressure. How to tell if his feeding tube was nearing empty and how much urine he was putting out per hour. I watched his pseudocyst drain to see how much purulent liquid was coming out and if the color, cloudiness, or thickness of it had changed. What kind of pressors he was on and what their levels were.
I washed his face, put cream on his limbs, filed his nails, hung cards on the walls, made sure the Pandora station was set to something he liked, and of course, joined rounds. And most days, I would sing or dance to at least one song around his bed. Not that Tom was awake enough to enjoy it. But who knew? Nurses would look down the hall and suppress a smile or laugh. They must have thought I’d lost my mind. How can that woman dance when her husband is so sick? I danced for my life. For ours. I was with him almost all the time, but I missed him. I missed sharing our lives, talking, laughing. He was either semi-comatose or delirious. It made me think of what caregivers of Alzheimer’s patients must go through every day when their loved ones are gone but still there. Tending to the details was something I could do. It gave me courage to soldier on.
For a few days after the procedure to insert the drain into his pseudocyst, Tom was feverish. His resting heart rate averaged over one hundred—high—which was indicative of tachycardia, or being “tachy,” meaning there’s a problem with the heart’s electrical system. His blood pressure took precipitous dips. So did his blood oxygen levels, which the nurses referred to as a “desat,” short for desaturation. I made copious notes on scraps of paper to keep track of things. The nurses allowed me to look over their shoulder at his electronic medical record, which included handy dandy ranges for each biomarker. Values that were abnormally high or low were asterisked. I’d grown accustomed to seeing those pages filled with snowflakes since Frankfurt. There were different fields for various kinds of tests that were run in panels, along with his microbiology cultures, which had several exclamation marks beside the description: “heavy growth of coccobacilli and heavy number of white blood cells. Moderate yeast cells.” A handwritten note was pinned below a whiteboard in Tom’s room. “Dr. Sharon Reed following patient. Please page X30778 in case of emergency.”
Many mornings, Tom slept and I absorbed what I could of medicalese by osmosis or by asking the nurses and residents, most of whom were more than happy to oblige. Day after day, the quiet cloister of rooms gave little hint of the struggles underway within. Many of the patients were alone. Some died. Although the doctors and nurses adhered to strict privacy rules about the health status of all the patients, I noticed that several rooms had a sign saying DROPLET PRECAUTIONS taped to their doors.
“Do droplet precautions signify that a patient has TB?” I asked Dr. Eric Scholten, the pulmonary and critical care resident who was on service.
“Not usually,” he replied. “These days, it’s mostly flu.”
“Influenza? Really?” I was amazed. I thought the flu typically hospitalized babies and the elderly. “Don’t people get their flu shots?”
“You’d be surprised. We have several patients in here who are in their prime, battling severe cases of the flu. People think it won’t happen to them. It happens every winter. And we’re in California. There are a lot of anti-vaxxers.”
Sometimes under the stress of a flu attack, the immune system grows weak and unable to fight off other disease organisms, or the immune system itself can go haywire attacking a secondary infection, causing sepsis and then organ failure. And sometimes someone’s unique vulnerabilities—a weak heart, obesity, a serious injury—made something like the flu that much riskier for them.
From inside Tom’s room, I surreptitiously watched one of the few other family members who came on a regular basis stop at the nurses’ station. She was a forty-something woman with a black pixie haircut and a pink jogging suit emblazoned with JUICY COUTURE. She wore sunglasses and a cup-shaped face mask as she entered Bed 9. The droplet precaution sign swung back and forth as the sliding door slid shut, and she approached a handsome man with dark wavy hair who was lying immobile on the bed. He was probably ten years older than the woman who I presumed was his wife, and his torso showed a slight paunch. The lower half of his face was almost covered by a ventilator and his skin looked waxy. There were several bags of dark fluid hooked up to his IV pole, which I knew meant that he was very sick. On the wall behind him was a family photo of him and this woman in happier times, with three little girls who all looked to be under five years old. As the woman settled into her chair, clutching her husband’s hand and a Kleenex in another, we exchanged glances. I know what you’re going through, I wanted to tell her.It hurts so much.
I felt another pang inside too; it was envy. I wished Tom just had the flu and could swap places with the man in Bed 9.
My cell phone pinged with a text from Chip.
You in Tom’s room?
Yup.
Be right up.
Tom was still asleep, something he seemed to do more and more of these days. I was happy to see Chip, hoping he could explain the microbiology report to me. But when I saw his face, I could tell right away that something more urgent was on his mind. He was renowned for always smiling or cracking a joke, even in times of crisis. Not today.
“So. The labs are back. They’re not what we hoped,” Chip said in a clipped tone, after he had donned gloves and gown. His shoulders sagged as he sat down on the stool beside Tom’s bed. He was not looking forward to what he had to tell me. Inside, I felt my heart start to race and stomach muscles clench.
“The Micro Lab ran the sensitivity analyses on Tom’s isolate based on a sample we took from his drain when IR inserted it,” he began. “His Acinetobacter is now resistant to the last three antibiotics, including the ones we use as a last resort, meropenem and colistin. We’re pretty surprised, since he’s only been on those for a few weeks.”
I was stunned. Resistant to everything? In a matter of weeks?
“What do we do now?” I asked Chip, feeling numb.
“The lab is still testing combinations of antibiotics to see if there’s any synergy. It’s going to take more time,” he replied. His voice did not sound very hopeful. “In the meantime, we just need to absolutely ensure that the pseudocyst fluid continues to drain, because we can’t allow it to spread.”
I pointed to Tom’s IV pole. Every metal prong was full, including colistin, meropenem, two other big-gun antibiotics, and an anti-fungal. Because they still had him on antibiotics, there was an assumption—on my part anyway—that the drugs were doing something.
“If the antibiotics aren’t working, then what are those for?”
Chip looked me in the eyes as he stood up to leave. “Those,” he said curtly, “are to make us doctors feel better.”
Oh, shit. The desolation in his voice trumped any hint of hope I’d held out. I’d had blinders on—medically assisted denial. For just a surreal flash, it all felt like elaborate theater, these trappings of treatment, and all of us dropped onto this stage with roles that none of us ever wanted: the patient, the patient’s wife, the desperate doctor.
“But Tom Savides said the other day that with any luck, once Tom’s infection is under control he might be able to come home and be trea
ted as an outpatient,” I countered. But nothing suggested luck was going Tom’s way.
“With all due respect to our colleagues, I don’t think they know what we’re dealing with here yet,” Chip responded, getting ready to leave. He stripped off his gloves and gown, and threw them hard in the trash, frustrated. “Tom can’t go home for the foreseeable future, unless, of course, we want to bury him. I, for one, am not about to let that happen.”
Neither was I, but resolve alone wasn’t going to save Tom. After I was sure that Chip had left, I pulled the brown curtains to Tom’s room closed, and laid my head down on his chest. And I cried. Hard.
The next morning, as I walked into the TICU shortly before eight a.m., I froze in front of the nurses’ station. The whiteboard behind their desk had no name beside Bed 9. I turned around and looked to see the room where the man with dark wavy hair had been lying just the day before. It was empty.
The man with the flu had died.
11
PUBLIC ENEMY NUMBER ONE: UNDER THE RADAR
The work of an epidemiologist is often to deconstruct disaster, working backward from an epidemic to identify how it happened, so we can prevent the next one. We are no strangers to worst-case scenarios for deadly diseases—AIDS, tuberculosis, cancer, heart disease. But even with that knowledge, the cognitive dissonance that has us, as ordinary humans, logically see one thing and emotionally believe another had continued to skew my expectations toward unjustified optimism.
The reality was that, on a societal scale, health leaders had buried their heads snugly in the sand, ignoring the growing peril of antimicrobial resistance (AMR). As if collective ignorance—or denial—would stave off a pandemic. I asked Chip if Tom’s Acinetobacter had to be reported to the CDC. After all, the Germans had to report it to their national health agency, and that was before it had become even more antibiotic-resistant. Chip told me that in the US, there were no reporting requirements for A. baumannii. National hospital reporting for MRSA was just now coming into effect, lagging well behind awareness of the threat it posed. Frustrated, I tried to google information on how many multi-drug-resistant A. baumannii cases occurred in the US each year and found nada, except for the CDC outbreak investigation on the military cases I had read about earlier.
I didn’t get it. A. baumannii was getting a reputation as one of the most formidable antibiotic-resistant pathogens. So, why didn’t this bug—and others like it—have reporting requirements, too? Without a superbug surveillance system, we had no idea when a new resistance gene emerged or how quickly it spread. We couldn’t track who had it, how they got it, or worse, learn lessons from patients that been treated. We were allowing A. baumannii to maintain its invisibility under the radar. And it happily did so, spreading quietly. Unreported. Undetected. And now, untreatable.
The scope of the AMR problem had crept up on me, even as an epidemiologist. Several high-level reports that were intended to mobilize a meaningful public health response had somehow failed to do so. There were still so many unknowns. How many people were infected or killed by superbug infections every year? Globally, the most recent estimate was 700,000, but a few years later, that number would be upped to 1.5 million. And even in most affluent countries with sophisticated medical tracking, no one really knew. Reporting was uneven at best.
I had been deluding myself, too, with naïve assumptions, like the idea that modern medicine could lick most of the common things that walk in the door: flu, food poisoning, infections you pick up on vacation. Science and statistics aside, our personal experience of Tom’s repeated brushes with parasites and other pathogens over the years had conditioned me to expect medicine—and Tom—to prevail. Even as a scientist who knew how dicey the microbial landscape could be, I generally considered bacteria to be inferior to viruses, less threatening. Apart from Mycobacterium tuberculosis, the bacterium that causes TB, most bacteria I dealt with had been fairly harmless. I’d streaked them on my Petri dish in my college microbiology class in the 1980s, no biohazard flow hood or protective gear required. I bought probiotic yogurt, understanding the need to promote the growth of friendly bacteria in our gut microbiome. And when they acted up? Antibiotics could handle it—just as Tom and I always had with our travel dose of Cipro.
We’ve put people on the moon and developed technology that can take your gall bladder out through your mouth. How could the best doctors and the best medicine at one of the top medical centers in the world be coming up short? How could we possibly be helpless against a species of bacteria that was once so mundane and harmless—wimpy, as Davey had said once. How the hell did we get here?
Thought to be a companion to humankind since our earliest forebears roamed the earth, A. baumannii and many other bacteria for the most part evolved with us—and within us—as relatively benign microbial hitchhikers. At every step, the goal of bacteria has always been straightforward: to go forth and multiply, evolving to match any challenges to survival. These included our migrations across continents and seas and the resulting changes in the flora and fauna of our habitats, as well as in the blood-and-guts microbiomes of our biological selves.
As our civilizations evolved, so did our microbial companions. Crowded living conditions, poor sanitation, air travel, and wars opened new opportunities for bacteria to breed, thrive, and spread relatively undeterred by medical science until Fleming’s discovery of penicillin in the early twentieth century. In short order (not even a blink in evolutionary time), scientists developed techniques to make and manufacture antibiotics for the masses. Suddenly pharmaceutical companies were cranking out drugs that could kill bacteria better than anything in human history. Bacteria had to pick up the pace of adaptations to match this new threat to their survival. And hoo boy, they did.
Nature equipped them brilliantly for the task: to detect threats, adapt quickly to defend themselves, and pass along their genetic playbook to their progeny and other bacteria. We measure human evolution in millions of years; bacteria do it in minutes. Antibiotic resistance can spread via two routes: reproduction and ordinary contact. As bacteria multiply through binary fission—one cell dividing into two new ones—the new generations of bacteria carry the mutations forward in a process called vertical transmission. Bacteria can also acquire resistance genes through horizontal transmission, as they encounter other bacteria in the air, or those that travel with us on objects or in environments we share.
Perhaps the scariest version of this community gene-sharing involves the plasmids—those Pokémon disks of DNA that can contain multiple genes for antibiotic resistance. A. baumannii is especially adept at picking up plasmids from other common bacteria, like E. coli or Staph, continually expanding its collection of antibiotic resistance genes that it passes on to its progeny.
Resistance genes confer what amounts to molecular chemical weaponry, arising from spontaneous genetic mutations that block or disable the threat. Bacteria can produce enzymes to deactivate an antibiotic. They can reroute an incoming antibiotic and dump it outside their cell wall. They can modify their own architecture to close off access points—receptors—that antibiotics use to attack them. If an antibiotic is designed to disrupt the bacteria’s cell wall, any protective barriers, or its reproductive cycle, the bacteria can reconfigure itself to fend off the attack. Some bacteria can even “hibernate” to avoid a predator. They share defensive intel with other bacteria through the use of electrical and chemical messaging, called quorum sensing. Under attack, bacteria that have developed the right mutations repel the attack; those that haven’t are done in.
Unaware of the invisible threat of AMR, people pass antibiotic-resistant bacteria along simply by coughing, hand-to-hand contact, or touching surfaces where the bacteria have set up shop—like Pokémon Go, but with the unsuspecting gamers catching superbugs. That’s also how overuse of antibiotics in livestock cultivates resistant bacteria, contaminating the animals, the environment, and the food products that people handle and eat.
Concern about AMR was lon
g dismissed as alarmist, despite Fleming himself having warned of it from the beginning. The first sign of trouble came in 1940, when a strain of E. coli was found to deactivate penicillin by producing an enzyme that destroyed it. Within two years, several strains of Staphylococcus aureus showed penicillin resistance in hospitalized patients. But labs were discovering new and stronger antibiotics far faster than bacteria were developing resistance, at least at first.
We call it Big Pharma now, a $446 billion enterprise in the United States alone, but the industry as we know it was barely advanced from the age of snake oil potions and pills at the turn of the twentieth century. Antibiotics became a large part of what put the “big” in Big Pharma. And with war on the horizon, there was big money to be made in manufacturing these new wonder drugs. Anne Miller’s case in March 1942 was a watershed moment in the commercial history of antibiotics. Penicillin was still not in large-scale production and was such a small-batch drug that the 5.5 grams used to treat her—roughly a rounded teaspoon—amounted to half of the US supply of the drug. Within a year, new manufacturing technology was developed that allowed for mass production. By 1945, penicillin was in widespread use, prompting Fleming to sound the alarm again.
“The thoughtless person playing with penicillin is morally responsible for the death of the man who finally succumbs to infection with the penicillin-resistant organism,” he wrote, after he and his colleagues received the Nobel Prize that year. It fell on deaf ears among industry, physicians, patients, and policymakers who were not keen to cut back.
Between 1940 and 1962 alone, pharmaceutical companies introduced more than twenty new classes of antibiotics to an eager market. In practice, that meant the release of hundreds of new drugs, because each class contains many related subtypes, each one tweaked in some way that tricks the bacteria, at least for a while. It was easy to believe that there was simply no end to the ingenuity of pharmaceutical research and development. New antibiotics soon followed: streptomycin, chloramphenicol, the family of tetracylines, erythromycin, and the cephalosporins. So what if bacteria were developing resistance? the thinking went. We’ll stay a step ahead by continuing to develop new drugs.
The Perfect Predator Page 10
