How the Queen Astrid Military Hospital processes phage requests

Issue 31 | June 7, 2019
9 min read

The Queen Astrid Military Hospital in Brussels has treated patients with phages since 2007, but lately, they’ve had a lot more phage therapy requests. This week, we’re highlighting a recent report describing who’s doing the requesting, what kinds of infections they’re seeing, and how they handle all these requests.

In case you missed it, we’ve written about phage therapy in Belgium before. (Fun fact: it’s been one of our most popular Capsid & Tail articles to date!)

Here’s the main source for this issue.

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How the Queen Astrid Military Hospital processes phage requests

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Phage microbiologist and co-founder of Phage Directory
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Jessica Sacher is a co-founder of Phage Directory and has a Ph.D in Microbiology and Biotechnology from the University of Alberta.

For Phage Directory, she takes care of the science, writing, communications, and business aspects.

The Queen Astrid Military Hospital in Brussels, Belgium (QAMH) has been treating patients with phages since 2007 (under the Declaration of Helsinki). Until recently, most of these patients came from the QAMH itself (mostly from the burn unit). However, between April 2013 and April 2018, they’ve seen a huge upswing in phage therapy requests from not just outside the hospital, but outside the country.

Quick stats

Time period analyzed: April 2013-April 2018
Requests for phage therapy: 260
Patients treated with phages: 15

Who initiated requests for phage therapy?

Patients: 71%
Doctors: 26%
Family members of patients: 3%

How did people get in touch with the QAMH?

Through e-mail, post, or telephone. Now, there’s a dedicated email address for phage requests: pt@mil.be

Where were these patients from?

The Netherlands: 67%
Belgium: 19%
France: 7%
Germany: 2%
Luxembourg: 1%

How old were the patients?

Mean age: 57.9 years
Most prevalent age group: 60+ years (61% of patients)

What kinds of infections did people request phage therapy for?

  • Urinary tract infections: 32% (chronic bladder infection, neurogenic bladder)
  • Lower respiratory tract infections: 24% (cystic fibrosis, bronchiectasis, chronic obstructive pulmonary disease, asthma)
  • Bone and prosthesis infections: 12% (osteomyelitis, osteitis in diabetic foot, infected traumatic fractures, hip and knee prosthesis infections)
  • Ear, nose, and throat infections: 9% (chronic sinusitis, chronic otitis)
  • Skin and soft tissue infections: 9% (burn and chronic wound infections, surgical wounds, diabetic foot ulcers)
  • Abdominal infections: 4%

What kinds of pathogens were most prevalent?

  • Urinary tract infections: mostly E. coli
  • Lower respiratory tract infections: mostly P. aeruginosa
  • Most other infection types: E. coli, P. aeruginosa, S. aureus

A few definitions

Multidrug-resistant (MDR): resistant to at least one agent in three antimicrobial categories
Extensively drug-resistant (XDR): susceptible to only one or two antimicrobial categories
Pandrug-resistant (PDR): resistant to all agents in all antimicrobial categories

Not all requests were for bacterial infections

11 requests were for non-bacterial or non-infectious ailments like arthritis, interstitial cystitis, cirrhosis, collage colitis, and irritable bowel disease

Not all infections were multidrug-resistant

P. aeruginosa: 7% MDR, 11% XDR, 7% PDR
E. coli: 47% MDR, 5% XDR, 0% PDR
S. aureus: 21% MDR, 0% XDR, 0% PDR

So most phage requests concerned non-MDR organisms?

Correct.

What does this mean?

Under the Declaration of Helsinki, patients should only receive unproven therapies if standard ones are ineffective, meaning most of these patients should not receive phage therapy. The patients described in this report were treated from 2013-2018, when the QAMH operated under the Declaration of Helsinki, and thus these patients were not eligible for phage therapy.

What criteria did the QAMH use to determine whether a patient qualified for phage therapy?

  • Must be infected by S. aureus, P. aeruginosa, and/or A. baumannii (the QAMH has potent phages against these species)
  • Must have at least a multidrug-resistant bacterial infection (as described above)
  • Must have no other therapeutic options

What happens once a request is received?

  1. The patient is asked to fill out a form (more medical information)
  2. If the form is filled out, infectious disease specialists and microbiologists meet (“multi-disciplinary meeting #1”) to discuss the case and decide if the patient qualifies for phage therapy
  3. If the patient qualifies, an infectious disease specialist consults with the patient (physical exam, patient history, bacterial samples collected)
  4. The patient’s samples are sent to the clinical lab for culturing, isolation and identification
  5. Phage susceptibility is tested with a phagogram
  6. If the strain is phage-susceptible, a treatment plan is proposed to the patient and the treating physician
  7. Multi-disciplinary meeting #2 is scheduled to discuss treatment protocols and patient follow up

How many patients got phage therapy?

15 of the 260 people (6%) who put in requests received phage therapy.

The breakdown

260 requests
245 rejected
15 patients received phage therapy

Reasons for rejection

  • 70 did not provide the additional medical information requested
  • 124 involved pathogens that QAMH had no potent phages against (mainly Enterobacteriaciae)
  • 46 involved pathogens that were still susceptible to antibiotics (or the patient had other therapeutic options)
  • 5 were rejected at the phagogram stage (non-susceptible to QAMH phages)

What happened with the rejected patients?

Most were referred to other phage therapy centers.

Have the results been published?

One case was published in 2017. The remaining cases will be published soon (grouped according to medical indications, and authored by the treating physicians).

Sneak preview: no serious adverse events were observed, and in general, phage therapy seemed helpful.

Were antibiotics used concurrently?

Yes, with the exception of one case.

Why didn’t patients answer the request for more information?

The authors suggest that they may have not been able to (it’s possible that treating physicians may not have provided the required health information for their patients due to a lack of confidence in phage therapy).

What is QAMH doing to help ensure fewer patients get turned away in the future?

  • Developing online tools to help inform health care professionals about phage therapy
  • Starting research programs to isolate and characterize phages against the strains that patients came in with that the QAMH had no phages against (due to the high species diversity, they estimate they will need to collect and characterize hundreds of phages)
  • Working toward implementing the magistral phage framework (formally approved by the Belgian health authority in 2018), which does not depend on antibiotic treatment failure

Why the recent upswing in requests?

The authors attribute the recent upswing to the airing of two prime-time phage therapy documentaries in the Netherlands in 2017.

There was also another one in 2019!

Main source:

Djebara, S., Maussen, C., De Vos, D., Merabishvili, M., Damanet, B., Pang, K. W., … & Pirnay, J. P. (2019). Processing Phage Therapy Requests in a Brussels Military Hospital: Lessons Identified. Viruses, 11(3), 265. DOI: 10.3390/v11030265 | Link

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