Isolating phages from a culture plate
There’s exciting news in the world of phage therapy and antimicrobial resistance! Jerry Nick, MD, of National Jewish Health, and Graham Hatfull, PhD, University of Pittsburgh, announced a patient’s cure from a Mycobacterium abscessus lung infection with phage therapy.
What are phages? They are viruses that infect bacteria and can lyse (or kill) them without the need for antibiotics. While their use goes back more than a hundred years, they fell out of favor with the discovery and growth of antibiotics—which are flashier and more profitable. As antibiotic resistance is a growing problem globally, interest in phage therapy has been renewed. More than 2.8 million antibiotic-resistant infections occur in the US alone each year, with 35,000 deaths. Antimicrobial resistance (AMR) is considered one of the top 10 global public health threats by the World Health Organization. The stagnant drug development pipeline compounds the problem of AMR as pharmaceutical companies abandon antibiotic research for more lucrative drugs for either chronic diseases or “lifestyle” drugs.
M. abscessus is a notoriously difficult to treat bacteria related to TB. Lung infections are often fatal despite the use of prolonged courses of toxic antibiotics. (This group of bacteria are called “non-tuberculous mycobacteria,” or NTM).
The first successful treatment of M. abscessus with phages was in 2019. Then Isabelle Carnell-Holdaway, a 17-year-old with cystic fibrosis (CF), was treated with a genetically modified phage from Hatfull’s lab after her lung transplant became infected. She lived for several years after.
In this current case, Jarrod Johnson, a 26-year-old with cystic fibrosis had chronic lung infections with multidrug-resistant (MDR) P. aeruginosa and methicillin-resistant S. aureus (MRSA). He then developed an M. abscessus infection which prevented him from getting a lung transplant. This is very similar to the problem that Mallory Smith faced, although her infection was due to a highly resistant Burkholderia infection. I described her course in my article Salt in My Soul. Transplant centers regularly reject patients with multi-resistant bacterial infections from consideration for a transplant, which is the patient’s last option.
Johnson received phage therapy, in addition to antibiotics for 500 days. Within 2 months, there were various signs the treatment was working, and after a year, his infection was felt to be totally cleared. He received a double lung transplant, continuing on phages through his recovery. He is now off all treatment and continues to do well; he has been able to resume a normal life.
As Hatfull explained, “patients are in desperate need of a lung transplant because of CF. The mycobacterium infection was not only bad but stopped him (Johnson) from getting a transplant.” Following the phage treatment for more than a year, his sputum cultures remained negative (didn’t grow the bacteria), and he was able to receive a double-lung transplant.
Greg Hatfull examining isolates in his lab
Hatfull also described a recent immunocompromised patient with a widespread Mycobacterium chelonae skin infection that had failed many treatment attempts. This patient was also successfully treated when a phage was added to his regimen. They had to use a single phage, called “Muddy,” as no others were found to be active against his mycobacterium.
One of the problems with phage treatment that Hatfull described is that some patients mount an immune response to the phages that is quite potent in neutralizing the phages. While the second patient developed neutralizing antibodies, he continued to show improvement. Hatfull excitedly noted, “That's one of the landmark aspects of that report. We used only a single phage” without detecting any resistance.
“It also goes to show that some of the assumptions that we had about how to do all of this were probably incorrect. The assumption that we needed to use multiple phages and a cocktail for mycobacterium infections…turned out to be wrong…And that's why it's partly why I think these kinds of case studies…can just be extremely informative, and at the same time you see a patient who gets substantial clinical benefit.”
Hatfull was careful to add that he wasn’t going to “evangelize” about phages replacing antibiotics. He views them as a valuable new tool being added. A number of patients have failed phage therapy. He notes these patients are critically important in learning more about using phages.
When the treatment works, “for both patients and physicians, this is a huge relief over using toxic antibiotics for long periods of time,” Hatfull concluded.
There is still much to be learned about phages as therapy for resistant infections. While, very fortunately, phages can be of great value in treating some infections, they are not a “magic bullet” that will treat all infections or that will replace antibiotics. We urgently need more funding for further research on this approach to fighting antimicrobial resistance.
