Phage, Combination Antibiotic Treatment For Resistant Pseudomonas aeruginosa Infection
Erlinda Ulloa, MD, discusses a severe case including how they secured the phage treatment, and her experience with the investigational therapy.
Erlinda Ulloa, MD, a staff physician at Children’s Hospital of Orange County (CHOC) in Orange, oversaw a very complex and challenging case that involved a 19 year old young woman whose initial presentation was for acute myelogenous leukemia. The patient had experienced cardiorespiratory collapse, requiring cannulation for ECMO. The patient was initially transferred to a nearby hospital for intensive care and ECMO and transferred back to CHOC after a prolonged stay of about 2 months as her condition stabilized throughout her hospitalization.
The patient developed a skin infection from an antibiotic-resistant strain of Pseudomonas aeruginosa. The patient developed multiple severe complications, including extremely painful, necrotic skin lesions. These lesions appeared about 5 to 6 months after her initial presentation, and they were secondary to a rare and severe condition called calciphylaxis.
“The skin lesions became infected with multidrug resistant organisms, including a particularly difficult New Delhi metallo-β-lactamase (NDM)-producing Pseudomonas aeruginosa. Ultimately, these infections, combined with her systemic challenges, made her care extremely complex,” Ulloa said.
Ulloa’s team included infectious disease pharmacists, oncologists, and plastic surgeons. And with FDA-approved antibiotics ineffective, they turned to an investigational, novel antibiotic combination, cefepime-zidebactam,1 which is in clinical trials, as well as phage therapy, a novel treatment platform that uses viruses to attack bacteria.
“We ended up turning to phage therapy rather quickly when we learned that our patient’s Pseudomonas isolate was pan resistant, and we had no viable FDA treatment options. So, at that point, we were pretty desperate,” Ulloa said.
Finding Phage Therapy
Although there are a growing number of phage therapy clinical trials in the US, there are no treatments that are FDA approved. And for what is available, it has to be done through special permission from the FDA. Ulloa says they were fortunate in terms of everything coming together including the medical professionals she worked with and the timing.
“I reached out to several academic centers, and was fortunate to connect with Dr Daria van Tyne, who is an associate professor of medicine at the University of Pittsburgh. Her lab has a library of manufactured phages, and we were able to identify rather quickly a suitable phage which allowed us to move more rapidly through the FDA approval process…it took about 6 to 8 weeks to find a phage, which is lightning speed compared to perhaps other patients in cases.”
Treatment and Recovery
“We ended up treating her intravenously, and that treatment was given for six weeks. As I previously mentioned, she did have wound infections, and so we had also considered doing topical therapy,” Ulloa said. “We tried it a couple of times. It was very challenging, due to the amount of pain that she was in. Ultimately, it was nearly impossible, so we abandoned the topical phages."
Their innovative, team-driven treatment, spanning multiple modalities, ultimately saved the patient’s life. The patient has fully recovered and is doing well.
“After a very long hospital stay starting in May of 2023 she was able to go home in October of 2024. her wounds have fully healed, which is a huge milestone, and importantly, she is in a much better place, both physically and emotionally,” Ulloa said.
Takeaways
From her experience, Ulloa has a couple of takeaways.
"I would say it's crucial to familiarize yourself with the process of obtaining phages and the FDA regulatory requirements. I do recommend working closely with a clinical research coordinator at your local institution that can help you with the necessary steps. If the need for phages is urgent, I would consider connecting with centers that have established manufactured phage library. In my experience, I feel that they can often provide phages more quickly than those focused solely on screening,” Ulloa said. “And then my second piece of advice that when it comes to treatment, is to go big or go home. Phage therapy often leads to the development of neutralizing antibodies, so the patient can develop neutralizing antibodies that make the phages ineffective, and the microorganism can also develop resistance…It's crucial to optimize the treatment in the first two weeks to ensure the best possible therapeutic outcome.”
She also says she is grateful for not only her colleagues at her institution, but also thankful for the help at other institutions, the phage developer, and the antibiotic manufacturer as they were able to secure both the phage and the antimicrobial treatment for free.
“Overall, the experience, I think, was a very powerful reminder of that when patients are facing difficult or life threatening infections, how the medical community can really come together to offer innovative solutions,” Ulloa said.
