Loss of mother launches global effort to combat antibiotic resistance

In November 2017, days after her daughter Mallory Smith died at age 25 from a drug-resistant infection, Diane Shader Smith typed a password into Mallory’s laptop.

His daughter gave it to him before undergoing a double lung transplant, with instructions to share any writing that might help others if she did not survive.

The transplant was successful, but Burkholderia cepacia – an antibiotic-resistant bacterial strain that first colonized her body when she was 12 – took hold. After suffering her entire life from cystic fibrosis and battling an invincible infection for 13 years, Mallory’s body couldn’t take it anymore.

In the fog of grief and pain, Shader Smith found herself looking through 2,500 pages of a journal her daughter had kept since high school. It chronicles Mallory’s hopes and triumphs as an athletic, rambunctious student at Beverly Hills High School and Stanford University, as well as her private despair as bacteria ravaged her system and sapped her considerable strength.

In the years since, the journal has become a source of comfort for Shader Smith, who has traveled the world speaking about the growing threat of antimicrobial resistance. It’s also now the inspiration for two new projects that she hopes will spark greater understanding of the public health crisis that ended her daughter’s life prematurely and could cost millions of lives additional people.

“Diary Of A Dying Girl” is an excerpt from Mallory Smith’s own writings, which chronicles her 13-year battle with an antibiotic-resistant lung infection.

(Genaro Molina / Los Angeles Times)

On Tuesday, Random House published “Diary of a Dying Girl,” a selection of entries from Mallory’s diary. The same day took place the launch of the World AMR Journala website collecting the global stories of people battling pathogens that cannot be defeated by our current pharmaceutical arsenal.

In the United States, approximately 35,000 people die each year from drug-resistant infections. according to at the United States Centers for Disease Control and Prevention. Worldwide, antimicrobial resistance directly kills approximately 1.27 million people each year and contributes to the deaths of millions more.

Despite the growing toll – and the prospect of possible push in superbug deaths – development of new antibiotics has stagnated.

Shader Smith is acutely aware of what we stand to lose when medicine can no longer save us.

“I don’t want to live in a post-antibiotic world,” Shader Smith said. “Until people understand what’s at stake, they won’t care. My daughter died from it. So I care deeply about it.

Over the past 50 years, opportunistic pathogens have developed their defenses faster than humans can develop drugs to combat them.

The misuse of antibiotics has played a significant role in this imbalance. Insects that survive exposure to antibiotics pass on their resistant traits, leading to more resistant strains.

As crucial as they are, antibiotics do not give developers the same financial incentives as other drugs. They are not intended to be taken long term, as are medications for chronic conditions like diabetes or high blood pressure. The most powerful ones should be used as rarely as possible, to give bacteria less chance of developing resistance.

“The public does not understand (the) magnitude of the problem. Antimicrobial resistance is truly one of the greatest public health threats of our time,” said Emily Wheeler, director of infectious disease policy at the Biotechnology Innovation Organization. “Today, the antibiotic pipeline is already insufficient to address the threats we experience, without even accounting for the continued evolution of these microbes over the years. »

Despite the global nature of the threat, Shader Smith said, the response from public health officials is curiously disjointed.

For one thing, no one can agree on a single name for this problem, she said. Different agencies approach the problem with an ‘alphabet soup’ of acronyms: World Health Organization uses AMR as a shortcut for antimicrobial resistance, while the CDC favorite AR. Medical journals, doctors and the media alternately mention multi-drug resistance (MDR), drug-resistant infections (DRI) and superbugs.

“It doesn’t matter what you call it. We all have to call it the same thing,” said Shader Smith, who works as a publicist and marketing consultant.

Since Mallory’s death, Shader Smith has made it his mission to get people and organizations working on antimicrobial resistance talking to each other. For the Global AMR Diary, she tapped a dozen agencies working on the issue, including the CDC, the WHO, the European Center for Disease Prevention and Control (the equivalent of the CDC in the European Union ), the Biotechnology Innovation Organization and others.

Antimicrobial resistance can “seem abstract given the scale of the problem,” said John Alter, the department’s external affairs official. AMR Action Fund, one of the organizations involved in the project. “Knowing that millions of families are going through hardships similar to those experienced by Mallory right now is simply unacceptable,” he said.

“Not only does this first-hand experience help those who might be going through a similar situation, but it also reminds those charged with creating solutions and healing who they work for.” It’s not just test tubes or charts,” said Thomas Heymann, chief executive of the Sepsis Alliance, another contributor.

The stories in the online newspaper are often heartbreaking. A 25-year-old pharmacist from Athens had to suspend her cancer treatment when an extremely resistant strain of the virus Klebsiella attack. A veterinarian in Kenya was left permanently disabled after contracting resistant bacteria following hip surgery. Around the world, routine outpatient procedures and illnesses quickly become deadly when opportunistic microbes take hold.

Mallory was 12 when his doctor called to confirm that his cultures were positive for an extremely resistant strain of cepacia, a form of bacteria widely found in soil and water. The pathogen can be deadly for people with underlying conditions such as cystic fibrosis, a genetic disorder that impairs the ability of cells to effectively clear mucus from the lungs and other body systems.

Life expectancy for people with cystic fibrosis has increased since Mallory’s diagnosis in 1995, with many living into their 40s and beyond. THE cepacia reduced this possibility for her.

“It’s all we’ll ever have,” Mallory wrote in June 2011, at the end of her first year at Stanford, “so if you’re not actively pursuing happiness, you’re crazy.” And I don’t think I would have this perspective if I didn’t have resistant bacteria that might kill me. »

A shrine dedicated to Mallory Smith. She battled drug-resistant bacteria from age 12 to 25, all the way through high school and then Stanford. (Genaro Molina / Los Angeles Times)

Mallory’s intuition that her journal might be useful to others was prescient. “People can easily understand and relate to real-life experiences,” said Michael Craig, director of the CDC’s Antimicrobial Resistance Coordination and Strategy Unit. “The Global AMR Diary takes this approach and develops it from a global perspective, increasing the potential to deliver these critical messages to more people around the world. »

An earlier version of Mallory’s journal was published in 2019 under the title “Salt in My Soul: An Unfinished Life.” The new book includes entries that Shader Smith said she wasn’t ready to tackle immediately after Mallory’s death: those that dealt with depression and private despair, concerns about relationships and problems body image issues complicated by chronic illness.

It also includes a coda on phage therapy, a promising advance against AMR.

As cepacia overwhelmed Mallory’s system in the weeks after her transplant, her family got an experimental dose of phage therapy. Widely used to treat infections before the advent of antibiotics, phages are viruses that destroy specific bacteria. The treatment came too late to save Mallory’s life, Shader Smith writes in a final chapter of the book, but her autopsy revealed that the phages had begun to work as intended.

The systems that bring new drugs to patients evolve slowly, Shader Smith said, and “Mallory could have been saved if they had evolved more quickly.” » His mission now is to make sure that is the case.

“Mallory died six years ago. Six years is a long time, day by day,” she said. “And I never took my foot off the pedal.”