Christ. I ran my hand across my face; my beard was long and ragged, like Rumpelstiltskin. My hair hadn’t been this long since the sixties, and I could feel hollows in my cheeks and beside my eyes that weren’t there before. But my arms, legs, and belly were puffy. From the neck down I could pass for the Pillsbury Doughboy. Davey explained that I had edema, which meant my blood vessels were leaking fluid into my tissues. The docs were giving me a diuretic to rid me of the extra fluid, and I had a catheter in so that I didn’t have to pee in a urinal every few minutes. I was falling apart between the seams.
The insides of my mouth felt like the Sahara. Maybe because I had just been walking in the desert for one hundred years. Or had I? I knew no one could survive in the desert that long.
What was real, and what was I imagining?
Before, I could have sworn there were hieroglyphics on the walls, but that was in my head. But that toy stuffed phage on the windowsill? Call me crazy, but it looks an awful lot like an Ankh, the Egyptian symbol for Life.
26
THE DARWINIAN DANCE AND THE RED QUEEN’S PURSUIT
April 1–6, 2016
I wish my five a.m. call to the nurses’ station had been an April Fool’s joke, but it wasn’t. I had lain in bed in the dark using my cell phone as a night light, and hit 7 on the speed dial. Tom’s night nurse, Larry, was in his room when I called, so I held for a few minutes listening to Muzak before ending up talking to the charge nurse, Mary.
“We were debating earlier about whether to call you or not,” Mary admitted. “Tom had a rough night. He desatted at around midnight. He’s back on full pressure support.”
“What?!” I spluttered. Desat meant the oxygen levels in his blood were too low—again. We had started to see signs of that yesterday during PT. I pulled out my ponytail band and gave my head a shake, trying to wake up. “Does he have a fever? Do you have a WBC from this morning’s chem panel? Is he back on the vent?”
“Yes, no, and no,” replied Mary, handily. His temperature had spiked at 103.5. She didn’t have the full chem panel, but his WBC count had been trending up through the night. I got the picture. Septic shock. Again. What was this now? The sixth time? I’d lost count.
Fuck, fuck, fuck.
Carly was still asleep. Danny and Frances had returned to the Bay Area the day before. We’d thought Tom was out of the woods, at least enough for the kids to begin to resume some semblance of their own lives again. They’d each left a lot hanging to be down here. I looked at the mountain of dirty clothes that was overflowing from the hamper and made a split-second decision what to wear. Stooping down to pull out my favorite gray hoodie, I gave it a sniff; it could live to see another day. I threw it on with a pair of velveteen leggings and padded to the kitchen. Within five minutes, I nuked yesterday’s leftover coffee and poured it into a travel mug, fed the kitties, and grabbed my car keys. Breakfast could wait. Besides, my stomach was doing flip-flops.
When I entered the TICU, the whiteboard behind the nurses’ station showed that Joe was assigned to us again today. He was 1:1; one nurse for one patient. That assignment was reserved for the sickest of the TICU patients, which Tom hadn’t been for weeks. As I approached Bed 11, my worst nightmare unfolded.
The room was empty. No Tom, no bed. Rosie was in there mopping the floor. There were only two possibilities. Tom was dead, or he was getting a procedure of some kind. If it was the latter, it was serious enough that they couldn’t do it bedside.
“Rosie, where’s Tom?!” I asked her in a panic. She looked at me and shook her head.
“Don’t know,” she replied sadly, looking at the floor, and kept mopping.
I ran back to the nurses’ station. It was one of the few times when no one was there. I looked at the clock.
Shift change. Dammit.
I paced the floor for a few minutes, and then pulled out my phone to text Chip.
Before I could hit the Send button, Joe entered the TICU and saw me standing there stricken.
“Joe! Where’s Tom? What’s happening? Is he…??”
Joe grabbed both my hands in his and looked me in the eye.
“Steff. Calm down,” he said quietly. “He’s getting a CT.”
Oh. That made sense. If he was septic, we needed to figure out the reason, and quick. But another CT meant that they had likely given him contrast, the imaging dye that was used so that the radiologists could read the films better. Contrast was hard on the kidneys, and that was the last thing Tom’s kidneys needed right now.
My phone buzzed. It was Chip texting. Are you in the TICU? I am coming up. No smiley face emoji this time.
Chip strode through the double doors of the TICU a few minutes later, and we conferred in Tom’s empty room.
“I just read the CT with radiology,” he told me in his matter-of-fact tone, the same way he would tell me that he had eaten scrambled eggs for breakfast. “Tom’s biliary bed drain has migrated into the hepatic parenchyma.”
I blinked. I only understood two words of what he had just said, but it was enough. Drain migrated.
“You mean another one of his drains slipped?” I asked him.
“Yes,” Chip replied. “Drain three.” Of the five. “IR is going to reposition it, stat.”
“Oh, for crying out loud. So, what now? After drain one slipped, he went into a coma and we almost lost him,” I reminded him. As if he could forget.
“Yes, but that was before the phages,” Chip said. “He’s stronger now. Although I have to talk to you about that.” His expression darkened. “Theron and Biswajit ran some studies on Tom’s more recent Acinetobacter cultures. Theron called last night to tell me that his bacteria is now entirely resistant to the Texas phage cocktail, plus it’s also resistant to every phage in the Navy’s cocktail except one. As of today, we will stop using the Texas cocktail and start administering the existing Navy phage into Tom’s abdominal drains, too, rather than IV alone.”
Within a few weeks, almost every phage in the two cocktails, and each cocktail as a whole, had lost activity against Tom’s isolate. No more shiny halos.
“Oh my God,” I whispered. “How could it become resistant so quickly?” But Scientist-Me knew why. We think of evolution over eons, but in the microbial world, it can happen overnight.
“It’s the perpetual Darwinian dance,” said Chip. “The pressure from the phages selected for mutations in the bacteria that could evade them. Given Acinetobacter’s doubling rate, their microbial army had plenty of time to come up with a new escape mechanism. I have a hunch that what they’ve done is drop their capsule. And if they have, they might have left themselves open to a new attack.”
Chip was referring to the protective sheath that some bacteria, including A. baumannii, have covering their cell wall. Capsules can be a virulence factor because they give the bacteria an edge with genetic tools to change or block receptors, strengthen the cell wall, or tweak other features to enhance its prowess and defend against intruders, like antibiotics and phages. The capsule also carries water to keep the bacteria hydrated and helps pick up new resistance genes from other organisms the bacteria encounters. Dropping its capsule could be a big deal.
But I was only half listening. I was now officially freaking out. Even if it had dropped its capsule, the Acinetobacter had won this round, fully resisting all but one phage. And without those phages to keep the pressure on, the Acinetobacter could surge again.
Since Tom was already having another septic shock episode, maybe the superbug had already surged again. It might be too late for a new round.
“Isn’t there anything else we can do?” I asked Chip, pleadingly.
“Already taken care of,” Chip replied in his clipped tone. “Theron got the green light from his CO to start another phage hunt, this time using environmental samples.”
I drew a blank. Beside me at the nurses’ station, Joe looked up from his paperwork.
“He means his commanding officer,” he replied.
I nodded,
remembering that Joe had been a military nurse.
“So it’s full steam ahead?”
“Yep. All hands on deck—the poop deck,” Chip kidded in an exaggerated version of his southern drawl. Quintessential Chip. But in this case, miraculously, the bureaucracy was working in our favor.
Chip resumed a more serious tone. “The Navy’s last cocktail was drawn from their phage library. Now Biswajit has already started screening phages obtained from local sewage samples. If he finds any, he’ll need the time to characterize them and purify them to the FDA standards. Then we get a new eIND for the new cocktail, and we’re good to go. We could have a new phage cocktail within a week.”
A week. Tom could be dead by then. I didn’t want to seem ungrateful, but in the ICU, battles for life were lost in the space of a heartbeat. A week felt like forever. My face fell, belying my terror.
“If I’m right, the timing should work out okay,” Chip reasoned, trying again to assuage my fears. “What I was getting at a minute ago is that the more recent Acinetobacter cultures from Tom’s drains look different when they are cultured, which is why I suspect they’ve dropped their capsule to evade the phages. Biswajit and several of his colleagues from the Navy and Army just presented findings on a similar arms race between A. baumannii and A. baumannii–specific phages. The A. baumannii capsule contained the phage’s receptor for entering the cell,” Chip paused to rotate his thumb and forefinger clockwise, like he was turning a key into a lock. “So, once the bacteria mutated and lost their capsule, the phages couldn’t enter the bacterial cell anymore. But the bacteria suffered a genetic penalty.”
I finished his sentence. “The A. baumannii mutant strain was less pathogenic now. The Red Queen hypothesis, right?”
Chip raised his eyebrows. I gave him a smug little smile; I had read the conference proceedings, too.
“Exactly,” he said. The Red Queen hypothesis refers to Alice in Wonderland and the imperious Red Queen character, who tells Alice that “it takes all the running you can do, to keep in the same place.” Evolutionary biologists used this literary analogy to explain how all creatures—predator and prey—must constantly adapt and evolve simply to survive. With his background in evolutionary biology, Tom would love to hear about this, if it wasn’t for the fact that his body was the military theater for the invisible battle playing out.
Just then, the double doors to the TICU swung open and a transport team pushed Tom’s bed through on their way back into Bed 11. Tom’s face was flushed and feverish, and he looked exhausted. When he saw us, he smiled weakly. As Joe hooked him back up to the cardiac monitor and adjusted his pressor settings, Chip and I took positions on either side of his bed.
“Oh, honey,” I murmured and squeezed his hand. “I’m so sorry you are going through this again.”
“I am, too, Tom,” said Chip. “But we already know what’s wrong. The drain in your gallbladder took a little walk through your liver. IR is going to reposition it for you today, and you should be back up and at ’em in no time.”
Tom looked at Chip and his lower lip quivered.
“I’m not sure I can take much more of this,” he whispered laconically, squeezing my hand tightly. I knew he was on the verge of tears.
“I know,” Chip said quietly, his voice full of sympathy. “You have endured one of the most harrowing clinical courses I’ve seen in all my thirty years as a physician. It’s been your strength and spirit, not just the phages, that has kept you alive.” He put his hand firmly on Tom’s bony shoulder. “You will get through this.”
Tom nodded almost imperceptibly. “Thank you,” he whispered weakly. “I really needed to hear that.”
Chip and I exchanged a look. Both of us knew that this was not the time to tell Tom that his infection had developed resistance to the phages he was getting, and that the Acinetobacter was morphing right now, right there inside him. We could only hope that if the newer mutant bacterial strain proved to be less pathogenic, his immune system might rally and keep it in check while the Navy team tried to generate a new phage cocktail.
That afternoon, Dr. Picel and his team in interventional radiology readjusted Tom’s drain. During the procedure, I imagined him threading the tube carefully through Tom’s liver to what was left of his gallbladder, where it could hopefully continue to drain off biliary sludge. I wondered if, on days like this, Dr. Picel felt more like a mechanic than a doctor.
Tom pulled through like a champ, but he continued to spike a fever for the next few days. Forty-eight hours later, his blood culture came back as expected: the dreaded A. baumannii had refused to surrender.
27
THE LAST DANCE
April 7–May 31, 2016
Biswajit’s new phage didn’t come from the Navy library or some exotic port at sea, but from the murky waters of a sewage treatment plant in Laurel County, Maryland. For all the sophisticated science in play back at the lab, this step in the phage harvest was more Huck Finn than high-tech: an empty half-gallon plastic milk jug filled with rocks and tied to a rope. Biswajit and Matt, a lab technician, trekked out to the treatment plant, one of their favorite hunting grounds. Perched at the edge of the water, Matt held the end of the rope and flung the jug out, let it sink and fill with the scummy water, then hauled it back and emptied the brackish brew into a half-dozen large, capped test tubes. If not exactly panning for gold, then fishing for phage.
And they found a good one. It was officially designated AbTP3Φ1, but quickly earned the nickname Super Killer—the perfect match against a superbug.
In the lab, when Super Killer was dropped into cultures of Tom’s bacterial isolate, the clear plaques that blossomed were the answer to everyone’s prayers. I remembered the German medics, Anneke and Inge, who’d come to Luxor to fly Tom out, and how, in his delusional state, he’d seen them as angels in combat boots coming to the rescue. They’d earned their wings. Now maybe this new phage could earn its halos.
It wasn’t fancy. In contrast to the phages in the original cocktails, which were myophages and had the longer, iconic contractile tails, this was a small, squat podophage with a short, noncontractile tail, consistent with the ancient Podoviridae family, subfamily Autographivirinae. So much for evolutionary upgrades. It added only one more phage to the cocktail mix, but initial tests for its activity against Acinetobacter indicated it was an efficient little bugger. Super Killer AbTP3Φ1 effectively killed the original bacterial isolate (TP1) and the two mutant strains that had followed (TP2 and TP3), which had become resistant to the phage in the first-round cocktail. Biswajit suspected that it targeted a different receptor than the myophages, which would make the new cocktail highly potent against A. baumannii. Not only that, the new phage also proved to be synergistic with one of those first-round phages, reviving its lagging activity against Tom’s isolate. Together they stopped the A. baumannii in its tracks, at least in the lab—the Biolog assay panel charting the growth curves of each phage and the isolate showed a flat line for the bacterial growth.
Once again, after this second-generation phage cocktail was cleaned and prepped and administered—about ten days later—we watched and waited, holding our breath that Tom wouldn’t have another relapse. Hours passed, then days. Tom developed sepsis again, but this time he rebounded quickly. His immune system was getting stronger, and he no longer needed blood transfusions. Other good news began to emerge in the weeks ahead. The culture from his pseudocyst and other drains revealed lighter bacterial growth of A. baumannii. Other tests also indicated that the Acinetobacter present now in Tom’s isolate was a shadow of its former self. Chip had been right.
I hoped the new phage would be enough to give Tom’s Acinetobacter a one-two punch. As we would eventually discover, Super Killer delivered that and more.
Every day in the TICU was the same old routine. Vitals. Meds. Blood draw. Rounds. PT. Bed bath. Sleep. Phages…
Of course, he was the only patient to get those.
“Billions of phages!” Tom crowed.
“Talk about going viral!”
We all groaned. Tom’s sense of humor had been one of the first things to recover.
None of us cared how weird this treatment was, as long as it worked. And it was working.
Chip, the Navy and CPT teams, and others exchanged constant reports from the battlefront that Tom and I could only imagine. They were monitoring activity underway in the trenches—inside Tom, that is—through the continuing data from blood draws and isolate samples. The Navy’s Biolog was dutifully cranking out graphs and images every fifteen minutes as each round of Tom’s isolate and the new phage cocktail were analyzed for the bacteria’s sensitivity and the phages’ virulence. The Darwinian dance was in full swing. Round by round, with the Super Killer in the mix now, the cocktails kept the selective pressure on, and the Acinetobacter was losing its grip.
By mid-April, Tom had improved enough that he no longer needed pressors to keep his heart pumping, and the TICU docs downgraded him to “intermediate” care status, meaning that he no longer needed “intensive” care. Never had a downgrade been so welcome. Given his track record in and out of medical mayhem, however, they opted to keep him in the TICU where the nurses could keep an eye on him a little longer.
We weren’t the only ones breathing a sigh of relief. I’d stayed in close touch with Ry, Jason, and the CPT team. Jason had confessed at one point that even if the phages fully cleared the bacteria, he worried that Tom’s body would never be able to recover. They’d been holding their collective breath, worried all along that we could still lose Tom. They’d just focused single-mindedly on keeping the hospital supplied with the Texas phages for the cocktails, as needed. But now, Jason said, “I think we can start breathing again.”
Recovery from near death is not a linear process. It might seem to go without saying that being as sick as Tom was for as long as he was, and enduring the physical and psychological suffering that went with it, would be traumatic. But with all the life-or-death medical crises from day to day, the ongoing trauma became more of an existential backdrop than a clinical concern that was acknowledged and addressed. A number of factors can contribute to delirium: metabolic factors, depression, medication, or an uncontrolled infection. Mayhem in the body expresses itself in the mind. Much later, we would learn about Posttraumatic Stress Disorder (PTSD) and how seriously ill patients and their families, especially those whose experience includes time in an ICU, may develop emotional triggers that continue to set off anxiety, depression, or a range of stress-related behaviors. Untreated, it may come and go in episodes that everyone tries to tough out until the “mood” passes, but ignoring it doesn’t really make it go away.
The Perfect Predator Page 27
