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The Promise of Bacteriophage Therapy to Fight Drug-Resistant Superbugs

— A conversation on living with cystic fibrosis and the threat of antimicrobial resistance

MedpageToday
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    Emily Hutto is an Associate Video Producer & Editor for ľֱ. She is based in Manhattan.

In this exclusive video, Claire Panosian Dunavan, MD, professor of medicine emeritus at the University of California Los Angeles, interviews Steffanie Strathdee, PhD, co-author of , and Jennifer Nelson, a cystic fibrosis patient colonized with Burkholderia cepacia, about antimicrobial resistant (AMR) superbugs and the promise of bacteriophage as a treatment option.

The following is a transcript of their remarks:

Panosian Dunavan: Hello and welcome, I'm Dr. Claire Panosian Dunavan.

Last month, ľֱ published a column I wrote called "Superbugs Pose a Deadly Threat to Cystic Fibrosis Patients." Today, we're going to continue talking about AMR (antimicrobial resistance), cystic fibrosis, and the exciting promise of bacteriophage with two remarkable people.

Steffanie, who I've known a long time, is a distinguished professor of global health at the University of California in San Diego [UCSD]. She now heads her University's center for Innovative Phage Applications and Therapeutics, AKA IPATH. This is something that Steff never imagined in her wildest dreams she would end up doing until her husband, Dr. Tom Patterson, spent months septic and often comatose in an ICU at UCSD with a totally resistant Acinetobacter baumannii isolate he picked up while traveling in Egypt.

Thanks to the relentless efforts of Steffanie and her colleagues at UCSD, Tom was miraculously restored to health with bacteriophage, which are viruses that kill bacteria.

That brings me to Jennifer Nelson. Jenn was diagnosed with cystic fibrosis [CF] as an infant and is now colonized with B. cepacia, which is arguably the most dangerous drug-resistant bacteria a CF patient can carry. Nonetheless, throughout her teens, Jenn was a competitive ice skater and dancer, and is now a major with 22,000 followers on Instagram. Regrettably, she also has severe complications involving her gastrointestinal tract and also has an ileostomy, a feeding jejunostomy, and uses TPN [total parenteral nutrition].

She has recently been discharged back home, and she has resumed skating and dancing. To me, she embodies an amazing will to survive and live each day as fully as possible [while] facing daily medical challenges.

So Jenn, I'm going to start with you. Just tell us a little bit: How you are feeling now, but also how did you feel back in 2016 when you were first told that you had the B. cepacia organism, and what are your hopes for receiving bacteriophage in the future?

Nelson: Hi. So right now I am luckily back home, which is great, and I am feeling better. I am on antibiotics, but they are just liquid -- so luckily not IV yet, so that's good. Just managing the challenges of my GI tract is definitely a struggle, but overall I'm feeling okay.

When I realized the significance of AMR was probably in early 2021 when my mom actually told me that we would be going to University of Pittsburgh Medical Center to meet with a doctor who specializes in phage therapy treatment -- through Diane, [who] had talked to my mom and kind of connected all of us together and -- it made me realize that this bug is bigger than antibiotics can handle.

Panosian Dunavan: And Diane, of course, is Diane Shader Smith, who is the mother of Mallory Smith, another very well-known cystic fibrosis patient who is the courageous author of two books and sadly died, after a lung transplant, due to B. cepacia.

Nelson: Yes.

Panosian Dunavan: So back now to Steff, what is the current status of bacteriophage for cystic fibrosis patients and also for AMR patients in general? And your relationships with CF patients I think are such a powerful motivator for your work. I just would love to hear your comment about that too.

Strathdee: Well, since my husband's case in 2016, phage therapy has really garnered a lot of attention, but it's still considered an experimental treatment in many Western countries, including the U.S., so it has to be approved by the FDA on a case-by-case basis.

There are situations that arise where we need to match phage to specific bacterial pathogens. Sometimes we can't find a match or the phage needs to be genetically manipulated, and there are manufacturing delays that have been very frustrating. So, that's the bad news.

The good news is that there are now over 90 registered clinical trials on phage therapy, several of which have focused on CF patients. So there is light on the horizon, but it's a slog. We need more resources.

Panosian Dunavan: I'm glad you're saying this. You are the person to be doing this. I've always been impressed with your energy, and now you have a whole new mission in life, as I said, which you never anticipated.

So, back to Jenn. Jenn has quite a perspective on just being a survivor as well as a champion communicator around all kinds of issues for CF patients. I think this is an opportunity for you to share your thoughts with a medical audience from the other side of the lens. What has it been like to have so much contact with high tech healthcare? What advice would you have for healthcare professionals and how they care for people like you? How do you get through each day just with all the challenges you face?

Nelson: So in the large medical world that we live in, as a patient and especially a young woman, it can be difficult communicating with so many different high tech doctors.

I'd say the most important thing is advocating for yourself and making sure you're on the same page with your team at all times. Bringing everybody together in a collaborative way as a treatment approach is really important, and it's important to me especially.

My advice to medical folks would be kind of the same thing -- advocate for the patient and hear what they're saying and put it as part of the treatment plan as well, because our thoughts and how we know our bodies, especially with cystic fibrosis, can really impact the treatment plan versus somebody who doesn't have cystic fibrosis.

What keeps me going day-to-day? I have a lot of different outlets, obviously figure skating and dance, but more on the everyday side of it is I have a great therapist, my family and my friends really encourage me to keep going. The CF community is fantastic, and I've connected with them on so many levels and so many different platforms.

Despite the challenges I face mentally, I tell myself every day that even in these really hard, trying times -- and the wait for my phages is really tough -- you have to kind of just find the good in every situation, even if it is one that is painful and difficult. Because I personally believe in every situation, even bad ones, there is something good somewhere that can come out of it. It's just finding that little sliver of light and holding onto it and clinging to it as you go through the journey, which is very important.

Panosian Dunavan: I see Steffanie nodding her head because she has daily contact with patients like you and she recommended you, and it's such a privilege to hear that perspective. Everybody in life faces challenges, but certainly the CF patients in your cohort -- some of the younger patients are going to benefit greatly from new drugs, I mean, there's a lot of amazing progress -- but you are facing a tough battle and we want to give as much support as we can to people like you and hear your voices.

So finally, Steff, pivot back in time. I know you have this passion you never planned on which is a story in itself. Again, is a great book to get to know you better, but what's our 5-year prospect do you think? And I guess we should just say a little bit about the huge global problem of AMR, which you can speak to.

Strathdee: Absolutely. Well, on a global scale right now, 5 million people per year are dying with superbug infections. That's going to grow to 10 million people per year by 2050, and that's thought to be a conservative estimate. That's one person every 3 seconds. So this is not a problem that's going to be going away, it's going to be getting worse.

And although we do need pull and push incentives to ensure that new antibiotics are entering the pipeline, we need alternatives and we need adjunct therapies like phage because phage can even be synergistic with the antibiotics, so you can actually use them to resurrect a failing antibiotic regimen that's been sitting on the shelf. That's very promising.

I think that in the next 5 years we're going to see a lot of these trials succeed, go into phase III clinical trials, and I do believe that that's going to be a combination of natural phage but also genetically modified or synthetic phage that are going to need to be used for B. cepacia and Borrelia and some of these other very difficult bacterial pathogens.

But I do think that we are going to see phage on the table alongside antibiotics as something that's going to be regularly used in medicine. It's become more well-known not just in the infectious disease community, but in other specialties like pulmonology and orthopedic surgery, because of people with prosthetic joint infections, or urologists who have patients with chronic urinary tract infections. These are the patients we're hearing from and we can help many of them.

It's really amazing when you see that we have saved 78% of people who are compassionate use cases who were otherwise going to die.

Panosian Dunavan: That is in itself such an amazing statistic. I can't thank you enough, each of you. Very powerful, and I also thank those who are watching this video.