Freedom from antibiotic purgatory? Salvage phage therapy for cure of spinal hardware infection
Issue 130 |
June 11, 2021
8 min read
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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Freedom from antibiotic purgatory? Salvage phage therapy for cure of spinal hardware infection
Stephanie is a postdoctoral researcher for the Iredell Group at Westmead Institute for Medical Research, NSW. Her project focuses on phage therapy for compassionate human cases (as part of Phage Australia), with a particular interest in Staphylococcal phages. In 2021, Stephanie completed her thesis titled ‘Exploring phage therapy for Staphylococcus pseudintermedius infections in canines’. Steph is always willing to chat about phage research and would like to connect with phage biotech companies.
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
IV antibiotics for 6-12 months, followed by hardware extraction if infection resolved.
Antibiotics + phage therapy
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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