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"What is my life?! Sometimes my life is so awful it's surreal." -- March 2014 entry in the book Diary of a Dying Girl by Mallory Smith.

Daily battles with sticky secretions, steatorrhea, and constipation. Respiratory treatments, mucolytics, endless antibiotics. Sudden gushes of hemoptysis. A vibrant life repeatedly interrupted by ever-lengthening hospitalizations.

Then, in November 2017, everything ended 2 months after Mallory Smith received new lungs at the University of Pittsburgh, the only medical center in the country that would operate on a cystic fibrosis (CF) patient chronically colonized with Burkholderia cepacia.

Although some may find its name unfamiliar, today, this is arguably the world's worst superbug in a modern CF sufferer.

So, what actually killed Smith following her long-awaited transplant? A virulent, necrotizing pneumonia fueled not only by B. cepacia's antimicrobial resistance (AMR) but its ability to trigger a massive release of inflammatory cytokines. As a final, desperate countermeasure, 24 hours before succumbing to "," Smith even received special viruses called bacteriophage meant to destroy her invaders.

But, for Smith, the sci-fi weapons arrived too late.

And yet, what a luminous life she lived for 25 years, cherishing family and friends, attending and graduating from Stanford, surfing in Hawaii, savoring romance, and chronicling every step of her journey on her laptop.

Only after Smith died did Diane Shader Smith read her daughter's intensely personal journal, then select excerpts that became , a posthumously published memoir. Then, just last week, Random House followed up with so readers could take one more look at Smith's short-but-extraordinary life.

Cystic Fibrosis, Then and Now

When considering the years that have passed since CF's by Dorothy Andersen, MD, it's hard to imagine another that has changed as much.

In the mid-1950s, affected infants often died before their first birthday, sometimes from malnutrition, sometimes from other complications stemming from faulty transport of chloride and water in their lungs, gut, and other organs. But by the 1980s and 1990s, CF youngsters were surviving far longer -- so much so that many in their 20s and 30s were cycling in and out of adult hospital beds with fevers and thick globs of sputum that often grew highly resistant strains of Staph aureus or Pseudomonas aeruginosa.

Today, 56 years is the of a baby with CF born from 2018 through 2022, according to the Cystic Fibrosis Foundation. Moreover, half of all currently affected 3-year-olds are likely to live into their 60s.

What accounts for this remarkable shift?

In addition to antibiotics, nutritional strategies, and daily respiratory care, what tops the list are new, effective CF transmembrane conductance regulator (CFTR) modulator therapies designed to correct the malfunctioning protein made by the CFTR gene. The first of these new medications, ivacaftor (Kalydeco), was approved in 2012. Then came new combinations -- tezacaftor-ivacaftor (Symdeko), lumacaftor-ivacaftor (Orkambi), and elexacaftor-tezacaftor-ivacaftor (Trikafta) -- that expanded treatment to other genetic variants to reach a broader group of patients with CF.

The recent 80% drop in CF lung transplants in the U.S. is further proof of the modulators' impact. Yet, despite their miraculous benefits, superbugs still pose deadly threats in the mucus-filled airways of advanced CF patients.

Superbug vs Superphage

In a moment we will segue to AMR writ large and the growing evidence that bacteriophage might soon eradicate certain deadly microbes in anyone from a CF sufferer to a war-wounded soldier to you or me. After all, there's no guarantee any of us won't someday acquire a dangerous drug-resistant pathogen.

But first, consider these about global AMR:

• Between 2000 and 2015, global antibiotic use increased by 65%
• In 2019, AMR contributed to roughly 5 million deaths worldwide
• WHO now includes AMR among its top 10 global health threats; without major interventions, AMR's death toll will likely double by 2050

One obvious battle-plan is to develop new antibiotics while curbing the excess antibiotic use that has long fueled AMR. That's an ongoing global challenge.

But another hope for patients in truly desperate straits is to find and receive viruses that destroy superbugs. This strategy has recently caught fire thanks, in part, to the power of one man's personal story.

I'm referring to , an electrifying book in which epidemiologist Steffanie Strathdee, PhD, describes how bacteriophages saved her husband's life after he traveled to Egypt and developed gallstone pancreatitis and a football-sized pseudocyst awash in multi-drug resistant Acinetobacter baumannii. Tom Patterson, PhD, was initially medevaced to Germany, and then spent months septic and (often) comatose in the ICU at the University of California San Diego.

Meanwhile, Strathdee and her medical colleagues called multiple phage researchers until a viral match was found at Texas A&M, was approved for experimental use, then administered. Twenty-four hours later, Patterson emerged from the jaws of death.

Today, Strathdee (recognized as one of Time magazine's 50 most influential people in healthcare in 2018) is the director of the (IPATH), the first dedicated phage therapy center in North America. In , she highlighted a recent uptick in clinical trials of bacteriophage. And, according to her review of case reports published from 1999 through 2022, phage-based treatments have now been used to treat antibiotic-resistant infections involving skin, burn wounds, the prostate, the urinary tract, the abdomen, bones, heart valves, lungs, blood, and implanted devices.

Strathdee has made an impact outside of the research world too. At the request of Shader Smith, Strathdee authored the epilogue of Smith's memoir, Salt in My Soul.

The Ongoing Fight Against AMR

It's fair to say that Smith and Shader Smith are now known to almost everyone in the U.S.'s close-knit community of CF patients, family members, and healthcare professionals -- Smith for her amazing grit and commitment to "living happy," and Shader Smith for her passion to spur greater awareness of the global AMR threat.

One of many AMR-impacted CF patients Shader Smith has personally touched is a 25-year-old woman from Ohio with B. cepacia. Thanks to Shader Smith, Jennifer Nelson is currently receiving high-quality care at the University of Pittsburgh Medical Center and one day hopes to receive a lung transplant preceded by bacteriophage therapy.

Last month, I spoke with the former ballerina and competitive ice skater. All in all, Nelson said, her childhood was "pretty normal" until her teens, when her disease worsened and required more antibiotics, then took another downhill turn in her early 20s. Today, Nelson has 22,000 followers on Instagram, but she also has an ileostomy, requires parenteral nutrition, and sometimes uses oxygen for the simplest of physical tasks. Meanwhile, her B. cepacia isolate has become almost fully antibiotic-resistant.

Nonetheless, Nelson continues to believe that even in the worst situations, something good can emerge or lies hidden within.

"Having a mindset like that," she continued, "when things are really awful, I've trained myself to think: what can this teach me? And then I search for that little 1% slice that could be positive."

Shader Smith also continues to find higher purpose following Smith's final battle. On May 7, 2024, she officially launched an initiative endorsed by CDC, WHO, and the European Centre for Disease Prevention and Control, among others, meant to raise awareness and shape new AMR policies through collective storytelling. For more, go to .

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