“Who heads up the other two labs?” I asked Chip. I was so sure I’d been thorough in my search. It seemed strange that I would have missed any that involved A. baumannii.
“Would you believe the US Army and Navy?”
I gave a low whistle. “You’re kidding me. The military is working on phage research? No wonder I hadn’t turned up any details on these investigators. Do you suppose it’s classified?”
“Well, I don’t know about that, but with a lot of their service members coming back from the Middle East with multi-drug-resistant infections, it makes a lot of sense that they’d already be working on this,” Chip said. “I have a call in to both later this afternoon.”
The next day, my cell phone blasted Aretha Franklin’s “Respect,” the ring tone I had recently assigned to Chip. I picked up and could tell right away that his dander was up—his slight Southern drawl had a bit of an edge.
“I spoke to the brass at the Army and Navy who are heading up their phage programs. Both were leery of getting involved in the care of a civilian.” He sighed, exasperated. “I told them that I would be the one overseeing the clinical protocol—that all they needed to do was to send the phage. They dug in their heels until I told them that I was more impressed with the Belgian military because they were offering their phages in a diplomatic pouch.”
This was quintessential Chip. My nickname might have been Pit Bull, but Chip was like a bulldog guarding a bone when someone stood in the way of what was best for a patient. This trait had made him a few enemies, but more often it earned him deep respect from patients and professional peers alike. Under these circumstances, respect could be the trump card.
“Bottom line—the Army is definitely out,” he said. “But I think I convinced the Navy to at least test their phage collection against Tom’s isolate. If there turns out to be any antibacterial activity, Theron Hamilton, the lieutenant commander, said he can cross that bridge when we come to it. The approvals will need to go right up the chain to the admirals.”
Theron would be putting a lot on the line to do this. But then, everything the Navy could learn about A. baumannii and how to treat it added to the Navy’s medical arsenal if it struck the troops, and it could prove valuable in a bioterrorist attack. So, helping Tom could be a win-win. Tom would have been the last person to volunteer for military duty back in the sixties, during the Vietnam War. Now that the battle was right under his belt, it looked like he might get a chance to volunteer after all.
“Well, I still call that progress,” I replied, holding the cell phone on my shoulder as I chased Newton away from the kittens’ food. He was getting a pot belly.
“Theron warmed up to me after I told him that he described their ‘Egyptian collection’ like a sommelier describes a fine wine,” Chip joked. “He told me he was ordering his lab to work double shifts this weekend, so they’ll test Tom’s isolate against their phages as soon as we can ship them a sample.”
So now we had not one lab but two working around the clock on the phage hunt, in the span of a few days. In fact, it was astonishing progress.
“I can hardly wait to tell Tom—even if he can’t hear me.”
We couldn’t know yet if the labs would find a phage that matched Tom’s A. baumannii, but we couldn’t just sit and wait for the answer. We had to move ahead in any ways possible with the administrative reviews and sign-offs so that if phages were found, there’d be no delay starting treatment. We had to be ready to report to the battlefront with new ammunition against this superbug.
We ended our call, each of us with a formidable to-do list. The micro lab had already shipped Tom’s isolate to Ry, and the CPT team would now send a sample of his culture to the Navy. I’d start work on the proposal for the UCSD ethics committee. We also needed to get a formal agreement signed to authorize the collaboration and materials transfers between UCSD and Texas A&M and a similar one for the Navy.
Chip’s list included following up with the FDA and working up a clinical protocol to establish formal guidelines for administering phages, assuming we got that far. He also needed to get approval from the UCSD biosafety committee. Typically, the administrative process for these various approvals took at least two weeks, sometimes months, but typically they are not a matter of life and death, as they were in Tom’s case.
As researchers, we both knew this drill, and we knew the steps and safeguards were there for a reason. The FDA is so often cast as the bad guy standing in the way of innovation, but in fact, those safeguards are important to protect us all. Dying patients and their families are vulnerable. It’s too easy to become victims to the likes of snake oil salesmen offering treatments that could kill rather than cure. Worse, in today’s world, the profiteers are coopting the language of science and medicine to legitimize their unproven claims and services.
Just as important, treatments that work need to be monitored so their success can push forward randomized clinical trials that will decide if they work on a broader scale. And we need to know when treatments don’t work so that the deaths of these patients are not in vain and treatment failures aren’t repeated. The process took time for good reasons, but it might be time that Tom didn’t have. One second too late and it would be game over. And we didn’t have any way to know when that second would be.
Two days later, my cell phone trilled. Area code 979. Although it was after eight in Texas on a Friday night, it was Ry. He wanted to introduce me to the four people in the CPT who were trying to save Tom. One by one they introduced themselves: Jason Gill, assistant professor and the CPT faculty member with the most experience doing translational phage research, who was a frequent collaborator of Ry’s; Adriana Hernandez-Morales, a doctoral student; and Jacob Lancaster and Lauren Lessor, both lab techs. I thanked them all profusely, and they went to work. So did I. That night I began drafting the proposal to get approval from the UCSD medical ethics committee.
All scientific research done on humans needs to be vetted and approved by an ethics committee. I had worked on scads of these proposals over the span of my career, but this one was different. This time there was only one subject: my husband. And this was a compassionate use request, which meant the team was asking the ethics committee to grant permission to use a therapeutic agent that had not been FDA approved on a patient who was dying.
I wrote about two paragraphs summarizing Tom’s case history from the day he fell ill over three months earlier, which included both medevac transports and his downward spiral into a coma after his abdominal drain had slipped a little more than a month ago. I jotted down the timeline and made a list of all the antibiotics he had been on. Tigecycline, meropenem, vancomycin, daptomycin, rifampin, colistin, azithromycin, teicoplanin, metronidazole, imipenem. He was a human pharmacopeia.
Next was the justification for compassionate use. My fingers froze above the keyboard. Paralyzed. I sat there for fifteen minutes, just staring at the computer screen, then the screensaver, which rotated photos from the trips Tom and I had done together. The two of us tracking mountain gorillas in Rwanda last summer. Hiking the Bandiagara cliffs in Mali. Dancing with the Huli wigmen in Papua New Guinea. I couldn’t write any more. Not a single word. I felt a paroxysm of fear, anticipatory grief, and panic come over me, and I broke down in huge, shuddering sobs.
Enough.
I sent Chip an email and attached the draft. “Over to you,” I wrote.
Spirit lagging, I took a time-out to Skype with Robert, who always left me feeling recharged. He was convinced that the phages were going to work.
“These Pac-Men are going to have a feast!” he exclaimed, rubbing his hands together with anticipation. “And one is like, a super killer, gobbling up more bacteria than any other. In all my fifty years of doing psychic readings, I have never had a more thrilling experience,” he told me earnestly.
“Yeah, it’s a thrill a minute for me, too,” I replied, and we both laughed. Maybe this superbug was going to meet its supermatch after all.
17
A HAIL MARY PASS
February 27–March 9, 2016
Six days into the phage quest, the feverish activity in the phage labs to find a cure for Tom matched that of the TICU to keep him alive. At the center of it all, Tom, still unresponsive in his nest of life-support apparatus.
At rounds the next day, the troupe of TICU docs on Tom’s case huddled near the doorway of Bed 11, where Tom lay intubated and wired for monitoring, alive but unresponsive. The group included the attending critical care doctor, Dr. Fernandes; the resident, Eric; the charge nurse, Marilyn; his nurse, Chris; and me. Chris read the summary from the report in front of him, then Eric briefed Dr. Fernandes on Tom’s latest cultures and lab values. The team leaned in.
“Creatinine is trending up, from 1.8 to 2.2,” Eric said, pointing to his laptop. His tone communicated escalating concern. The normal range is 0.6 to 1.2 in adult males. Dr. Fernandes leaned over to view the past week’s trend in creatinine levels, a marker of kidney function. The bar graph’s steep upward slope was not good.
“Better call in nephrology,” he told Eric. I knew what it meant. Tom’s kidneys were starting to fail. And given his condition, dialysis wouldn’t buy him much time, if any. Since Tom was already on life support for heart and lungs, dialysis would signal a terminal trifecta of system-wide organ failure—the beginning of the end.
Ordinarily, on rounds the team would stay just long enough for the update and then move on to conduct rounds at Bed 12. I was a fixture there by now, often asking questions to clarify technical aspects of Tom’s condition, his medical treatment, and care. But today, Dr. Fernandes and Eric looked first at each other, then to Marilyn and finally at me, with a question of their own.
“There’s a rumor you and Chip are planning some sort of experimental treatment involving viruses,” Dr. Fernandes began, his tone cautious but curious. “Can you fill us in? None of us have any experience with this, and we need to be in the loop.” All eyes turned to me.
For a moment, I was caught off guard—embarrassed that they might think I was questioning their abilities. But I saw in their eyes that they were desperate to save Tom and frustrated that they’d run out of options. There wasn’t much about modern medicine that the doctors in this world-class hospital didn’t know or weren’t experienced with, but the blind spot was understandable, since phage therapy had been sidelined decades ago in Western medicine. That might be about to change.
I explained that Chip and I had only enlisted the help of CPT and the Navy less than a week ago, and we didn’t yet know if they’d find any matching phages, or how long it would take. Dr. Fernandes and Eric listened, their expressions reflecting keen interest and natural skepticism. As a scientist myself, I knew that feeling.
“I know it’s a long shot,” I said. “And I know it’s risky. But I don’t see any alternatives being brought to the table.”
Dr. Fernandes nodded slowly. “Neither do I. To be honest, we are running out of options to turn your husband’s case around.”
It would be a Hail Mary pass with the quarterback blindfolded and less than a minute left in the fourth quarter, he added, but it was worth a try. “If you can pull this off, it may benefit a lot of other patients. So, you and Chip have my full support.”
I thanked him and promised to update his chief, Dr. Atul Malhotra, as well as the director of the TICU, Dr. Kim Kerr.
Left to ourselves, I brushed Tom’s hair gently and rubbed his forearms and legs with an extra thick cream. Then I took a pumice stone and exfoliated the bottoms of his feet, rubbing off layer after layer of calluses and peeling skin. “You’re finally getting that pedicure I’ve wanted you to get for years,” I told him, pretending he could hear me. Maybe he could.
At noon, I prepared to leave Tom in Chris’s capable hands, knowing that in a few minutes, two of our students would arrive to sit with him. Carly’s husband, Danny, had sent out the call online for this bedside vigil and used an online calendar tool for scheduling. The response from all corners had been overwhelming, and friends, family, students, and others showed up without fail for two-hour shifts, throughout the day and evening.
It was impossible to know whether Tom, in a coma, was in any way aware of their caring presence or anything I might do or say. But a few studies had suggested that comatose patients could sometimes hear, and that the sound of their loved ones’ voices aided their recovery. And Robert insisted that their presence and interactions were a vital connection to Tom, a grounding, human tether through his otherwise utter isolation in the mass of tubes, cables, and high-tech medical paraphernalia that enveloped him. Martin, the holistic healer, agreed. However difficult it might be to reconcile with evidence-based metrics, Tom had rallied unexpectedly in Frankfurt when his daughters flew over to be with him, even when most clinical signs indicated that he was dying. There had been other moments, too. Nothing you could quantify, but honestly, if modern medicine was down to digging through sewage for experimental possibilities, if some bedside company and one-way conversation held any potential for good, I didn’t need FDA approval for that.
Tom stirred briefly and moaned softly as I kissed him goodbye until tomorrow.
On my way out, Rosie, the TICU housekeeper, entered Tom’s room with her cleaning cart, as she did nearly every day. I had recognized her hobbled walk heading our way from way down the hall. I greeted her with a weak smile.
“It’s all yours, Rosie,” I told her, watching mindlessly as she swept the floor of Bed 11 clean, emptying into a biohazard bin the dustpan full of syringe caps, crumpled Kleenex, and the layers of dead skin that continually shed from Tom’s feet.
Rosie’s eyes met mine. “I’m praying for you and your husband. You are both so full of life,” she said gently. Her kindness, and just the mere thought of Tom as “full of life” made me choke back a sob.
The next day, Tom’s weakening state due to his lack of nutrition became a new focus of urgent attention at rounds. The tube that had been inserted through his nose when he arrived at the TICU wasn’t up to the task of handling his nutritional needs now. He was, in any practical sense, a starving man. However, the bigger, better type would mean another tube inserted in his abdomen, yet another potential site for infection that could instantly trigger more sepsis. After agonizing over what to do, I signed the consent authorizing interventional radiology to insert a new G-J-tube in his jejunum the next day, after no amount of hand-squeezing could coax a response from Tom.
Two days after the procedure, I sat with Tom bedside. He lay quiet, still unresponsive, but when I arrived I was dismayed to see that he was in wrist restraints. Not even fully conscious, he’d put up a fight against the vent tubing, and this was the only way to keep him safe. I accessed Pandora on the laptop and selected some of his favorite meditation music, Native American drumming. The warm tones of the drumbeat filled the room, a welcome contrast to the cold, syncopated beep of the heart monitor. Then suddenly, the blare of the cardiac monitor shattered the peace. Tom’s heart rate shot past 130, and his oxygen level dropped below 90. I smashed the call button. Chris had just come on shift and came running down the hall. Tom’s breathing had become rapid and shallow. His face turned red and shone with fresh perspiration. Chris and I looked at each other, read the signs, and came to the same conclusion at the same instant: more septic shock.
All along, there had been trouble adequately draining the infection sites in Tom’s gut. That afternoon, new blood tests, lab cultures, and CTs were conducted. A few days later, it would show that a fungus—Candida glabrata—which had been detected in the pseudocyst from the beginning was now present in Tom’s blood. Somehow the fungal infection had breached the walls of the pseudocyst and was spreading. This meant that Tom had candidemia, which Davey reminded me had a 50 percent mortality rate. Tom was now under siege by bacteria and a fungus, while we were trying to save his life with billions of viruses. For an infectious disease epidemiologist, life seemed more and more like a cruel joke.
Some mornings, the hospital’s sunny atrium and palm-lined promenade was invisible to me in my rush. It could seem overly earnest, too sunny, too optimistic, when I was hurrying through for the umpteenth time up to Tom, who was listing more to the dark side. That doorman with the snazzy double-breasted suit who used to look so welcoming was starting to make me think of a pallbearer. I’d walk in as other families walked out with their loved ones newly discharged, holding balloons, and I tried to be happy for them, but it was hard wondering if Tom would ever get out. For all the attention paid to time, all the ways the TICU staff sliced and diced and measured it by heart rates and shift changes and scheduling and bowel movements, in a real sense, time stood still. It had been three months since Tom fell ill in Egypt, two months since he’d been airlifted from Frankfurt to Thornton, and it felt like forever. Now, suddenly, the promise of the phage cocktails had quickened the sense that something was finally happening. But until the phage arrived and Tom could be treated, nothing could happen. Instead of feeling time oozing formlessly around us, it was now electric, supercharged, tension mounting in the wait for someone to flip the switch. It had been two weeks since we’d hatched the phage therapy plan. Depending on my mood, the days felt like either a countdown to blastoff or the last dark minutes of the Doomsday Clock.
When I arrived at the TICU the next day, Tom lay in Bed 11, so still that I had to check if he was still breathing. Yep. The cardiac monitor showed his heart rate at 113, tachy, but stable. Blood pressure 90/65. Not great, but no change since my usual five a.m. call to the nurses’ station a few hours earlier.
“Has he been awake at all since shift change?” I asked Chris, who’d been assigned to Tom for a second day. Chris had a warmth and presence that never failed to transform our sterile stage into a human one. So much about the ICU focuses naturally on the essential—“keep them alive”—but Chris always went a step further, making minute adjustments in care to not only keep Tom alive but also keep him comfortable, actively make him better, even in small ways. He always took the time to explain ICU lingo to me in a way that didn’t feel patronizing. Chris had just finished brushing Tom’s teeth with a practiced hand and was getting ready to turn him on his side, as he was required to do every two hours to ensure that he did not get any “pressure wounds.” Bedsores.
The Perfect Predator Page 18
