Breathe easy: the remarkable story of David Cranston, AusHealth’s bacteriophage pioneer patient

When nasal surgery left Adelaide nurse David Cranston fighting a drug-resistant infection, traditional treatments offered little relief. Struggling to breathe and spending hundreds of dollars a week to manage his symptoms, he turned to bacteriophage therapy, a century-old approach now being revived as a potential weapon against antibiotic-resistant superbugs. David became the first patient treated by the AusHealth Phage Therapy Centre, an Adelaide-based research facility at the Basil Hetzel Institute for Translational Health Research. Researchers developed a personalised therapy that dramatically improved David’s quality of life — and now offers fresh hope to others suffering from similar infections.

The AusHealth Phage Therapy Centre was set up through a collaboration between AusHealth and Adelaide University.

David, you contracted a drug-resistant bacterial infection in 2016. What happened?

David: Following nasal surgery I contracted ‘pseudomonas’, which is a bacterial infection caused by the bacterium Pseudomonas aeruginosa. It stayed in my nose for two years, then went into my lungs and I went downhill pretty quickly. I visited my GP and respiratory doctor trying to figure out what I could do. It turned out I had bacterial colonisation rather than a true infection [where bacteria invade and multiply causing symptoms such as inflammation and fever etc.]. There was nothing they could do.

What was your quality of life like?

David: Within six months, I was down to 45 percent lung function, which meant I was always short of breath, even just walking around. I couldn’t speak in full sentences. I was on a lot of IV antibiotics but I’d always get a rebound effect – I’d come good, then all of a sudden the bugs would go ‘let’s party!’. That’s when there’d be huge amounts of mucus. At work, I was going into a quiet area every day to clear the mucus and make myself feel better for a couple of hours. I was spending nearly 100 bucks a day on chest physio just to get mucus out.

It was pretty miserable.

You work as a nurse – is that how you knew about bacteriophage?

David: I actually did some research online. Because I was colonised with bacteria rather than infected, I wanted to find out what could be done. That’s when I started researching online…

Now’s probably a good time to explain that bacteriophages are naturally occurring viruses that kill bacteria…

David: That’s correct. I managed to secure a broad spectrum bacteriophage from Europe which I self-administered. Then I saw my respiratory specialist and he prescribed Gentamicin, because phage therapy works better in conjunction with antibiotics. So I was inhaling them at the same time through a nebuliser [a machine that turns liquid into vapour].

I began to improve, so I knew something was working.

How did you come into contact with the AusHealth Phage Therapy Centre?

David: Through my research, I knew Professor Peter-John Wormald was investigating phage therapy here in Adelaide, and I contacted him about any upcoming trials with pseudomonas. I was keen to try something more targeted than just the broad-spectrum bacteriophage I’d used.

Professor Wormald was working with the AusHealth Phage Therapy Centre and was able to include me in the trials on compassionate grounds.

Professor Sarah Vreugde, can you describe how the Centre developed a treatment for David?

Sarah: David was actually our first patient. Professor Wormald had treated others before, but that was using phage from a third party to treat staphylococcus infection.

For David’s pseudomonas treatment, we developed a new phage cocktail.

Before anything else, we had to optimise our protocols; it’s one thing to experiment in a lab with phage, but when it comes to manufacturing phage to treat patients, it’s all about safety. We had lots of people working on it – including two PhD students and one postdoc pharmacologist – purifying the phages so they could be used in a nebuliser.

David, what did the treatment involve?

David: I had five days of antibiotics delivered by IV morning and night. For the phage therapy, they built a special nebuliser for me to inhale it nasally to kill the infection in my nose. I also had a separate regular nebuliser to treat my lungs.

How long did it take before you started noticing improvements?

David: I could feel it working within a couple of days.

Sarah: In combination with IV antibiotics, the phage was very effective: after five days we had an almost complete eradication from both David’s nose and his lungs.

We then settled on a second course of longer intravenous antibiotics together with the phage. While we didn’t see further reduction in the infection, there was eradication of four out of five of the strains he was infected with.

What was the final fifth strain?

Sarah: It was a mucoid-strain and difficult to eradicate. It’s another pseudomonas, but it creates a big slime – the mucus – which means the phage can’t find its target.

Since David’s treatment, we’ve encountered other patients infected with these mucoid strains, mostly people with cystic fibrosis and usually at quite a late stage of their infection.

Will you be able to treat it?

Sarah: We’re currently working on other phage protocols to treat it. Specifically, we’re looking to find compounds that can reduce the mucus produced by that bacteria. There’s promising data, but it’s a bit early to administer it. We’re hopeful there’ll be a new protocol to help soon.

It’s been nine months since your phage therapy, David. How are you feeling now?

David: Good! And that’s why I want to continue with treatment!

Since I had phage therapy late last year, I might need one good coughing session to clear my lungs every couple of months to reduce an overload of mucus. As for treatments, I’ve only had to use one course of antibiotics.

Sarah, were you happy with the outcome of the treatment?

Sarah: It’s a good outcome even though I would have liked to see an eradication of all strains. When you have multiple strains of infection at the same time, they exchange information as a group and become much stronger. That makes it much more difficult to treat the infection. So the fact that our treatment could eradicate most strains is exciting because it means that the infection as a whole becomes less damaging and easier to manage. And this is reflected in the fact that David feels better. But now that we know what the potential of phage therapy is and which strains in a real-life situation survive the treatment, we have a better understanding of what we need to do to further improve the treatment outcome.

David, would you recommend phage therapy to others in a similar position?

David: Oh, mate, yes!

And what’s next for you?

David: It would be nice to see what running is like again. It would also be nice to go a day without having to worry about where my ventilator is. So, it would be good to kill that last bug and see if I can improve even more.

At the moment I’m working on being at peak health ahead of hopefully doing another trial with the AusHealth Phage Therapy Centre. It might improve the outcome further.

Hopefully phage therapy keeps on getting better known and more available, not only to people in my situation, but in other situations as well. Professor Wormald said, if you can fix me, you can fix anybody!