A world-first study has shown how bacterial genomics is changing the way we treat patients with severe infections.
Bacterial infections can be recurrent and life-threatening. But a Victorian-led study shows that genomics can give doctors critical information no other test can find.
We talked with lead author Dr Stefano Giulieri – a Melbourne Genomics fellowship recipient – about what it means for patient care.
Genomics has been used in the fight against superbugs for some time – for example to track the movement of bugs within a hospital. How is your study different?
The idea here is to use bacterial genomics to support patient treatment, not just infection control. And that’s the game-changer – it’s precision medicine rather than public health.
Using genomics gives us a much deeper understanding of the bacteria that are infecting a particular patient: it’s like going from seeing a name on an ID card to reading a ten-page resume. That helps us prescribe the most appropriate treatment, and also make decisions about whether or not the patient may need invasive treatments such as surgery. It can also help avoid unnecessary antibiotic use.
Is this becoming more urgent with the rise of antibiotic-resistant superbugs?
It also works on bacteria that are completely susceptible to antibiotics. By sequencing the genome of infecting bacteria, I can anticipate which antibiotics are going to work. This is already being done elsewhere, in the management of tuberculosis, for example.
But in this study, we looked at treatment failure. A patient may have a bacterial infection and, despite starting a treatment, the bacteria are still there. We call that a persistent infection. Or maybe the bacteria first disappear and then they reappear – and that’s called a recurrent infection.
We can sequence the genome of the bacteria at various timepoints, and compare them over time. This shows us whether the same bacteria has come back, whether it has acquired mutations that make it more resistant to antibiotics or the patient’s immune system, or whether it’s a completely new bacterial infection. That’s information you cannot find without genomics, because the bacteria of the same species often looks the same in the hospital laboratory.
This approach was inspired by cancer genomics, which looks at driver mutations that cause tumours, and then further mutations that may lead to metastasis or resistance to chemotherapy. That’s common in cancer genomics but it’s not done in bacterial genomics.
We’re essentially looking at the evolution of bacteria in real time, in the human body.
Why did your study focus on golden staph bacteria?
Golden staph [Staphylococcus aureus] is the number one cause of bacterial infection deaths worldwide, with more than one million deaths each year. It has a tendency to persist, to linger, to cause complications like sepsis or spinal or cardiac infections.
Around 30% of the population are carriers of golden staph, but going from carrier to infected is very rare. But the risk is higher for young children - especially premature babies – and also for people int their 70s or 80s, people with co-morbidities like diabetes, cancer or kidney failure, or for people who have had medical implants like a pacemaker or prosthetic joint.
But the framework outlined in our study can be applied to any bacterial infection.
How is genomic testing used with superbugs? Here's a step-by-step guide.
Let’s talk about you for a bit. Why did you begin studying antimicrobial resistance?
I used to be a full-time clinician, working on bone and joint infections with orthopaedic surgeons. One problem I saw is that these infections are often difficult to treat or eradicate and can persist for years. So I was fascinated by this phenomenon of bacteria being able to persist for so long within a patient, and becoming resistant to antibiotics along the way.
I happened to see genomic research from Ben Howden from the Doherty Institute, and thought that kind of research could help me get a better understanding of these infections.
How did the Melbourne Genomics fellowship support your research?
It showed me how my research could be applied in a clinical setting. The fellowship got me to think about how it can actually be helpful for clinicians, and I discovered potential applications I didn’t think about before. For me, that was the game-changer.
It also gave me a sense of the complexity of implementing genomics in a hospital setting – for example, what type of ethics approval you need to get, which stakeholders do you need to get on board, how do you explain your work in simple terms and different ways?
Melissa Martyn also helped me design the survey that we used with clinicians around the world. The survey showed us the value of having real-time genomic information on bacterial infections. For example, clinicians told us they were unable to predict whether the bacteria had evolved based solely on their clinical presentation, and that in one-third of cases, they would change antibiotic treatment based on the genomics. So that’s an exciting potential impact.
What do you think are the next steps?
We’re looking to set up a service at the Doherty Institute’s Molecular Diagnostic Unit, where clinical laboratories send us bacterial strains, and we analyse them. We generate a report that a microbiologist can analyse and then send back to the lab.
Clinicians will need to be aware of this service and what it can bring for their patients who have bacterial infections. We also need to look at the health economics – how the cost of genomic testing compares with the significant cost of treating patients in hospital for recurring bacterial infections over weeks or months.
Read the full paper in Nature Communications.
Dr Stefano Giulieri is an infectious diseases clinician at the Royal Melbourne Hospital. The study was led by the Peter Doherty Institute for Infection and Immunity, and involved multiple hospitals in Victoria.