Kidney Transplant Patient with Recurring Infections Gets Viral Help
Maria Madrigal was born with polycystic kidney disease, although she did not know she had this hereditary condition until adulthood, when growing cysts caused organ failure. Initially, dialysis helped, but eventually Madrigal needed a donor kidney, which she received in 2017.
Before the kidney transplant, recurring infections occurred frequently. After the transplant, they returned, but this time it was worse. The invasive pathogen, a strain of Escherichia coli, was multidrug-resistant. It could not be treated even with the strongest available antibiotics.
“My health deteriorated. The more antibiotics, the worse it got. I felt like I was dying,” Madrigal said.
“I first met (Maria) in November 2018 when she was admitted for sepsis, and several times thereafter with a recurring infection,” said Saima Aslam, MBBS, Director of the Solid Organ Transplant Infectious Disease Service at UC San Diego Health and Associate Professor of Medicine at UC San Diego School of Medicine.
“Prognosis in terms of mortality is difficult to assess, but she had multiple hospitalizations for the same problem and was on almost continuous IV antibiotics—so certainly very poor quality of life, and she would eventually run out of treatment options, increasing the risk of dying from the multidrug-resistant infection.”
Phages on a cell
Colorized scanning electron microscope image of a cell being attacked by phages.
In January 2020, Aslam introduced the idea of bacteriophage therapy. Bacteriophages are viruses that specifically attack and kill bacteria. Aslam proposed treating Madrigal’s persistent and life-threatening infections with phages, an emerging treatment method that researchers and physicians at UC San Diego have been developing with remarkable success.
In fact, UC San Diego is home to the Center for Innovative Phage Applications and Therapeutics (IPATH), the first dedicated phage therapy center in North America.
“The center arose in part from a desperate, life-threatening experience with my husband,” says Steffanie Strathdee, PhD, an infectious disease epidemiologist, professor in the Department of Medicine at UC San Diego School of Medicine, and co-director of IPATH.
“He was on the brink of death due to a systemic bacterial infection that had defied all other treatments. An experimental phage therapy approved by the FDA on compassionate grounds ultimately saved his life. IPATH is about developing the therapeutic potential of phages and making them available to other patients when conventional approaches do not work.”
For every bacterial species on Earth, there is a phage that attacks it. Like other viruses, phages cannot replicate on their own but instead hijack the replication machinery of bacteria. They do this by attaching to a bacterium and inserting their genetic material, initiating a replication process that eventually splits the bacterium open and releases new viral particles in search of new targets.
For Madrigal, it would be about finding the right combination of phages to treat her specific bacterial infection.
The therapeutic potential of phages is not new. They were explored as a possible medical treatment in the 1920s and 1930s but were largely abandoned with the advent of antibiotics. The growing global problem of bacterial antibiotic resistance has fueled their resurgence.
In 2016, a team of physicians and scientists at UC San Diego Health used an experimental intravenous phage treatment to save the life of Strathdee’s husband: UC San Diego Professor Tom Patterson, who had become infected with a multidrug-resistant strain of Acinetobacter baumannii, an opportunistic and often deadly bacterium. The treatment worked, and Patterson recovered.
Since the Patterson case, researchers at IPATH, in collaboration with physicians at UC San Diego Health, have used phage therapy to treat multiple cases of antibiotic-resistant infections, including patients after organ transplants, with cystic fibrosis, or who use implanted medical devices.
In a paper published on August 27, 2020, in the journal Open Forum Infectious Diseases, Aslam, Strathdee, and colleagues describe the first 10 consecutive cases of intravenous phage therapy. In seven of the 10 cases, patients had a successful outcome.
Madrigal’s case is number 11.
For six weeks, Madrigal received infusions twice daily with a phage cocktail developed at Baylor College of Medicine in Houston. Her blood counts, as well as her liver and kidney functions, were monitored regularly, and she continued to receive an intravenous antibiotic.
After one week of treatment, Madrigal noticed an improvement in her health. Her appetite returned. She could walk faster. “I wanted to be active again.”
Madrigal’s phage therapy ended in August when blood cultures no longer showed E. coli. She also stopped taking antibiotics. Some fever spikes and elevated inflammatory markers prompted physicians to resume antibiotic treatment (Aslam is trying to identify the source of the fever), but her blood tests continue to be negative for the bacterium.
From Madrigal’s perspective, phage therapy was an unexpected lifeline: “I saw it as an alternative. I told myself: ‘I have nothing to lose by trying it. On the contrary, I could benefit from it.’ I did it with all the faith in the world.”
“Before phage therapy, I felt my future was uncertain. Actually, dialysis too. When you undergo dialysis, there are always setbacks. There are complications. It was a long process to get here. I went through a lot, the removal of both kidneys. But I was always very optimistic, had great confidence in myself and in the team behind me. All of that helped me to be here today feeling well.”
Aslam said interest in using phages to treat multidrug-resistant organisms is growing. Elsewhere, phage centers have opened. From the opening of IPATH in June 2018 through April 2020, the center’s physicians and scientists received 785 inquiries about phage therapy from other physicians, patients, and family members of patients. Of these evaluated requests, phage therapy was recommended in 119 cases, with IPATH faculty helping to connect treating physicians with phage laboratories, treatment protocols, and logistics. IPATH is also raising funds to develop a phage library with carefully characterized phages that can be used to treat patients more quickly.
But Aslam cautions that this is still a beginning: “Clinical trials are being planned to truly evaluate efficacy scientifically,” she says.
Translation of source: https://health.ucsd.edu/news/features/Pages/2020-12-02-one-for-the-phages.aspx
One for the Phages: Kidney Transplant Patient with Recurring Infections Gets Viral Help
By Yadira Galindo | December 01, 2020
