Freedom from antibiotic purgatory? Salvage phage therapy for cure of spinal hardware infection

Issue 130 | June 11, 2021
8 min read
Capsid and Tail

In our PHAVES seminar series last month, Dr. Laura Damioli and Dr. Greg Canfield (University of Colorado Anschutz) shared their experience treating their first patient with phage therapy for a spinal hardware infection. Here’s the recording, along with a recap by Stephanie Lynch!

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A post-doc position is available in the Parent Lab (Michigan State University) to work on mechanisms of phage attachment to enteric pathogens. Genetics, biochemistry, and computational approaches as well as single-particle cryo-EM will be combined to study the molecular mechanisms of host recognition. Interested candidates should contact Dr. Kristin Parent ([email protected]) with a CV and cover letter.
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Some of you may recall that, last year, I put out a call to contribute to a special issue of Pharmaceuticals on “Bacteriophages as Therapeutic Delivery Vehicles.”

We have 10 articles published or near completion already but there’s room for more. We’ve had the submission deadline extended to July 30th.

If you are doing any work or want to review work using phages that have been modified in some way to improve or create new therapies, your work will fit here. We have articles on phage encapsulation to improve delivery, phage use in cancer therapeutics, and luminescent reporter phages among others already so the topic is pretty broad.

More information about the issue is here or you can contact me, Paul Hyman ([email protected]) or Tina Schneider ([email protected]) or Bryan Gibb ([email protected]). I’m looking forward to hearing from you.

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This is Hala Ali, a postdoctoral researcher at Bacteriology Department, Animal Health Research Institute, Egypt. I am looking for sponsor lab to host me for 6 or 9 months as a postdoc scholar funded by Egypt. I am interested in developing novel phage-antibiotics strategy for combating MDR-S. aureus mastitis. Please email me at [email protected] if you know of any opportunities or may be willing to host me.

Freedom from antibiotic purgatory? Salvage phage therapy for cure of spinal hardware infection

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PhD Candidate
La Trobe University

I am a third year PhD student from La Trobe University, Melbourne, currently isolating and researching the use of bacteriophages for skin infections in animals. I have a background in Animal & Veterinary Bioscience and hope to continue research of bacteriophages as therapeutics within the veterinary or livestock sector. I am also currently developing and optimising the use of animal-alternative models for safety and efficacy trials of phage therapy. I am always willing to chat about phage research and would like to connect with phage biotech companies as I am interested in jobs within the industry sector.

PHAVES #16, a seminar by Dr. Laura Damioli and Dr. Greg Canfield (May 12, 2021)

YouTube video

Overview and highlights

The patient case

  • 80 year old patient, complaints of wound dehiscence (wound separation) following spinal hardware surgery to correct kyphoscoliosis (abnormal curve of the spine).
  • The patient also had medical co-morbidities, including recurrent UTIs, which placed a higher risk of infection following hardware surgery.
  • Cultures from the open wound found to grow 3 colony variants Pseudomonas aeruginosa, all with similar antibiotic sensitivity patterns.
  • A lack of wound healing after wound vacuuming, antibiotic treatment, and subsequent wound wash-out and muscle flap surgery. The drainage from the wash-out cultured Pseudomonas aeruginosa.

Challenges

  • Hardware infections are hard to treat due to Pseudomonas aeruginosa biofilms
  • Antibiotics aren’t good at sterilising the hardware, and the patient was not a good candidate for hardware extraction.
  • Quinolones are the only oral antibiotic with activity against Pseudomonas aeruginosa, however, the patient was a poor candidate for quinolones. Additionally, previous data shows that 36% of patients had intolerability to quinolones following prosthetic joint infections, with 43.3% of these experiencing adverse reactions

Options for the patient

  1. IV antibiotics for 6-12 months, followed by hardware extraction if infection resolved.
  2. Antibiotics + phage therapy
  3. Hospice care

The patient chose option 2.

Option 2: Phage Therapy

  • The three Pseudomonas aeruginosa strains isolated from the patient were sent to Paul Turner’s Lab (Ben Chan & Jon Koff) at Yale University.
  • Multiple lytic phages were found to lyse the clinical isolates of Pseudomonas aeruginosa, however, the 3 strains showed varying degrees of phage sensitivity.
  • 5 phages were chosen based on qualitative (spot test) and quantitative (killing kinetics, EOP etc.,) characterisation.

The treatment plan

  • Over an 8-week period, 4 different phage regimens were administered, either singly or in a phage cocktail combination (1 x 10^9 - 5 x 10^10). Between 5-100 mL of the phage formulation was administered, either into the patient’s catheter or spinal drain.
  • 2 hours after phage therapy, antibiotics were administered (as previous literature has shown that the order of phages/antibiotics matters).
  • New phages were chosen every 2 weeks (as it has been shown previously there is a fitness trade-off between phage resistance and antibiotic resistance).

Patient monitoring

  • Inflammatory tests (Biomarker of resolving infection)
  • Organ monitoring
  • CT scans of the spine

Results

  • Successful resolution of Pseudomonas aeruginosa infections. No sign of hardware of infection 60 days after treatment.
  • Recurrent UTIs on-going and C. difficile diarrhea.

June 2021 update: The patient is off all antibiotics, with no signs of recurrence of the hardware infection.

Audience question highlight

Q: The propagation strain of Pseudomonas aeruginosa harboured 7 prophages. Did you check to see if these excised and were present? Do you see this as a problem?

A: Yes this a potential problem, but was NOT observed in this study. Given the potential of induced prophages to horizontally transfer antibiotic resistance and toxin-associated associated genes to susceptible bacterial hosts, it might be important to use prophage-less bacterial strains for lytic phage amplification.

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Thanks to Atif Khan for help finding and summarizing this week’s job posts!

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