Episode 2: AMR

Diagnostics: Beyond the Lab

In this episode of Diagnostic: Beyond the lab, we talk to Colin Denver, CEO of SpeeDX about antimicrobial resistance and using diagnostics to target treatment. 

Hosts & Guests

Janet Silver

Cameron Groome

Colin Denver

 

Meet the Guests

Colin Denver

Colin is the Chief Executive Officer of SpeeDx and has years of sales experience working in the Life Science and Diagnostic fields. Colin first obtained a Bachelor of Science from Pepperdine University and then a Post Graduate Diploma of Management from MGSM. He started as Vice President of Sales and Marketing for SpeeDx, and working now as the CEO. Throughout his time in this position he is responsible for launching products in Europe, United States and Australia/New Zealand.

About SpeeDx

Founded in 2009, SpeeDx is an Australian private company with subsidiaries or distributors in the EU, UK, and US. SpeeDx specializes in molecular diagnostics that provide for improved patient management. Its real-time (qPCR) innovations drive market-leading multi-pathogen tests, and a portfolio focused on such “multiplex” diagnostics for sexually-transmitted infection, drug-resistance, and respiratory disease.

Microbix & SpeeDx Collaboration 

Microbix Biosystems Inc., a life sciences innovator and exporter, and SpeeDx, a developer of innovative molecular diagnostics solutions, have a collaboration under which Microbix is exclusive developer of Quality Assessment Products (QAPs™) to facilitate the registration and commercialization of SpeeDx diagnostic assays.

The collaboration began with support of SpeeDx’s diagnostic tests for infection with antimicrobial-resistant (AMR) strains of Mycoplasma genitalium (AMR MGEN), a widespread sexually-transmitted infection. They continue to provide products and services in partnership with some of the world’s largest diagnostics-makers and clinical labs.

About This Episode

[00:00:00] Janet Silver: Hello, I’m Janet Silver from Syntax Strategic. 

[00:00:11] Cameron Groome: And I’m Cameron Groom from Microbix Biosystems. Thanks for joining us for Diagnostics Beyond the Lab. On this podcast, we talk to industry leaders in scientific and health communities about discoveries, challenges, and what they see as the way forward in their field.

[00:00:28] Today we’re going to talk about antimicrobial resistance, AMR.

[00:00:34] Janet Silver: And Cameron what’s really interesting about AMR is according to the World Health Organization, this is a global health and development threat. In fact, they have declared it as one of the top 10 public health threats. 

[00:00:48] Cameron Groome: And this affects all of us. Antibiotics that drug use to treat bacterial infections are being used all around us and not just in humans, but also widely in pets and livestock. And with this usage comes resistance to those treatments. So, there’s a lot of work underway to do this. SpeeDx is a global leader in such work, and they’re part of the AMR Hub partnership between research and industry.

[00:01:17] So joining us from Sydney, Australia is Colin Denver, CEO of SpeeDx. Welcome, Colin. 

[00:01:24] Colin Denver: Thank you for having me. 

[00:01:25] Cameron Groome: Let’s start a little bit about SpeeDx. Can you tell us a little bit about the company and its work? 

[00:01:31] Colin Denver: Yeah, no, we’re an Australian molecular diagnostic company. We have proprietary technology in the field of PCR.

[00:01:38] So I think everybody, since the pandemic, is pretty aware of what PCR is, but what we really have in our technology, is an ability to multiplex. And especially when we talk about AMR, which is often a series of very complex genetic mutations or things that the bacteria have acquired to get around the antibiotics and how they work. You need to be able to put lots of those different targets into a single test. 

[00:02:02] And that’s what our technology enables us to do. And that’s what we’ve been able to apply into a number of fields that we’re looking forward to talking about today. 

[00:02:11] Janet Silver: Colin you spoke a little bit about what AMR is.

[00:02:14] I’m wondering if you can maybe go a little bit deeper for our audience. How has that developed over the years and what is SpeeDx doing about it? 

[00:02:23] Colin Denver: You alluded to it, I think, in the intro that we’re really at a point that is truly scary since the invention of antibiotics where we’re about to approach period of time where we could have untreatable infections. So, infections, that with the current antibiotics that we have available to us, are simply not able to secure the infection in patients. One of the, probably the prime examples of this would be gonorrhea. So, gonorrhea we’re down to the last line of defense and without an ability to recycle current options. So, options that may be able to treat some patients, but not all or indeed new antibiotic options. We’re really at a very difficult time, I think in the treatment, I would say of patients infected. 

[00:03:07] Cameron Groome: Indeed. Scary times. And Colin, certainly I’ve seen, in human and animal health fields, many cases of AMR emergence.

[00:03:16] Do you see it being limited to STIs or moving more broadly health? 

[00:03:22] Colin Denver: I think it’s been present in a number of other infections. Probably most notably tuberculosis, which I think is obviously a massive health concern across many both high income and low- and middle-income countries.

[00:03:34] But there’s others out there as well. In the case of if we look at mycobacterium, which is what tuberculosis is a species of, there’s other nontuberculous mycobacterium that are already resistant to the main lines of antibiotics that are used to treat those. And in many cases, patients that are infected with those non tuberculosis mycobacterium, they, they may have underlying health conditions like cystic fibrosis or other type of respiratory conditions where those resistant infections can really either severely impact their health or even kill them, which is very scary. 

[00:04:10] Cameron Groome: We know you’re quite right that this is a broad problem. Some of the work that you’ve done, at least the outset, is focused on sexually transmitted infections in antimicrobial resistance within that area.

[00:04:22] Can you talk a little bit about STIs and the health impacts of those?

[00:04:27] Colin Denver: I think STIs, I’ve talked a little bit about gonorrhea to start with, but there’s other STIs out there that have seen a significant increase in resistance to the frontline treatments or the syndromic treatments that are used by clinicians.

[00:04:41] And I think as people have looked at this more, the scary thing is especially since the pandemic, things have not gotten better over the course of the pandemic. And I guess a lack of focus on AMR, given all the other challenges that were going on with the covid spread as well.

[00:04:58] And I think ultimately now that we look back in STIs, there’s pathways that can be enabled by new and novel diagnostic strategies like resistance guided therapy that I think, have shown the pathway of how we can move ahead without the sort of silver bullet antibiotic that cures everything and how we can better tailor treatment to the individual infection that the patient has. So, I think that ultimately is a pathway that I think tailoring treatment options with the antibiotics that we have will really be the path forward for dealing with this significant increase in resistance that we’re seeing now. 

[00:05:36] Janet Silver: Colin, I just want to take that one step further in terms of diagnostics in the lab, and I’m just wondering are you finding, not just SpeeDx, but others, finding that there are other diseases, for example, that are becoming more known, if you will, because of the diagnostics and what you’re finding in the lab? I’m pointing specifically to MGEN as one. 

[00:05:56] Colin Denver: I think definitely if I look at MGEN diagnosis, so Mycoplasma genitalium diagnosis, it’s definitely come a long way in terms of the awareness of the bacteria as a cause of certain clinical symptoms within the STI space.

[00:06:10] And I think now that we’re able to go back and look at this infection, it truly is a bacterium that is pretty spectacular in its adaptability. It’s got the smallest genome of any bacteria out there, which means only a very few number of mutations that these bacteria can pick up can lead to significant changes in the bacteria that allows it to become resistant to the antibiotics that are being used to treat it. Again, it’s something that now that we are looking for it, and now that we are studying it more generally and in a routine diagnostic space, we’re able to better tailor how clinical pathways can be created to address the infection.

[00:06:49] Cameron Groome: Could you talk a little more about MGEN, Colin? Folks that I’ve spoken to have been very surprised to learn that there’s this very common, sexually transmitted infection they never heard of. So, tell us a little bit more about MGEN and clinically its relevance and how does this come about?

[00:07:07] Colin Denver: So, the funny thing is, and again the golden rule of diagnostics, is if you don’t look, you won’t find it. When you look back at the studies that have been done over the years of patients that are presenting to STI clinics or to general practice with certain symptoms, like cervicitis or urethritis, the way it used to play out is you’d probably have two thirds of these patients would be infected with either chlamydia or gonorrhea. And about one third of these patients would be not otherwise detected, or there was no known cause of the symptoms. 

[00:07:37] With the advent of better diagnostics, so sort of over the last five to ten years, but definitely within the last five years, what we’ve seen from the literature is of that third of patients, a large percentage of those patients were actually infected with M. genitalium.

[00:07:53] And again, of those third of patients that would come back, or of the total amount of patients that would come back with recurrent symptoms, there was a significant amount of those patients presenting back to the same clinics where they had their initial treatment that were actually infected with M. genitalium.

[00:08:10] So it was taking multiple courses of antibiotics to get a successful treatment outcome. And again, I think that’s where diagnostics plays a big role, is actually identifying what they’re infected with as the first priority, and then being able to tell whether what they’re infected with is going to be successfully treated with the antibiotic that you choose.

[00:08:31] Cameron Groome: Flying blind we don’t know what’s causing your symptoms and certainly need to just keep randomly trying to find a therapy. 

[00:08:41] Colin Denver: And again, sometimes the treatment was actually the same therapy again, but just at a higher dose. So again, you’re already infected with a resistant bacterium and you’re trying to treat it again with the antibiotic that it’s already resistant to.

[00:08:56] So it really was a very difficult time for some of these patients to resolve their symptoms and again, talk about it later on. But the impact on the health system was that these patients were presenting multiple times with the same infection and in many cases spreading this infection because they thought that they were cured after the first dose of antibiotics.

[00:09:18] Cameron Groome: Colin, can you delve a little bit more into the role of advanced diagnostic tests for organisms such as MGEN and how critical the accuracy of those tests is? 

[00:09:29] Colin Denver: Again, it’s something that as clinical pathways evolve and as more of the issues with treatment come about such as MGEN and these sorts of unresolved cases that were causing symptoms, the ability for clinicians to have more data is really important. So, I think diagnostic companies that work with these clinicians, such as the way SpeeDx has worked within the sexual health clinician universe. I guess, yeah, we knew there was a problem, we knew that there needed to be a new diagnostic prepared. And again, you have to create a diagnostic that is able to diagnose the infection consistently, but also able to be run in a lab setting. So, the labs have a number of criteria that need to be met before they can adopt the assay. And indeed, they have a number of things that are different additional components to the diagnostic test that they need to run in, to ensure quality of the assay initially and throughout the course of their offering the service to the clinicians.

[00:10:28] Janet Silver: Colin, if you don’t mind, I just want to go back to something that you said a bit ago, and that’s with regards to gonorrhea and being able to treat gonorrhea. And I’m wondering if, because of the concerns and being able to treat this STI, if we’re now looking at AMRs across the board, for all STIs, for example, and what you’re finding?

[00:10:49] Colin Denver: Yeah. I think the focus is definitely gonorrhea just because I think it has been identified so many times as an issue. So, there’s quite an interesting graphic if you ever want to look at it, that shows the time by which gonorrhea has developed resistance to a new antibiotic that has been used.

[00:11:06] And I think the one that sticks out to me is that there was a drug released in the late nineties, or an antibiotic released in the late nineties where within a year antibiotic resistance to that drug had developed to over 90%. So, it’s something that is supremely flexible in what it can do, gonorrhea.

[00:11:23] And I think ultimately it probably presents the greatest challenge from both the treatment and a diagnostic sense to overcome all of these mechanisms that gonorrhea has within its genetic makeup. In terms of other issues within the space of STIs, there’s others that come through, but I think those are probably the biggest ones that we face within gonorrhea. 

[00:11:46] I think there’s other challenges in other bacteria, helicobacter pylori are another one that has multiple antibiotics that you to use now. I think they’re up to, to quad therapy. So, there’s four different antibiotics that go into to treating helicobacter, and I think there’s even resistance within those treatment options as well. So, I think there’s definitely other high level severe disease-causing bacteria that definitely need new and innovative approaches that combine diagnostics and the right treatment at the right time. 

[00:12:15] Cameron Groome: Fully agreed Colin. Is MGEN, or mycoplasma genitalia, is that a good example of how AMR profiling can actually help define treatment protocols and get to more effective outcomes?

[00:12:28] Colin Denver: I really think it is, and I think it’s come very much through partnership, and I think the partnership between the various players that you need to be able to deliver what ultimately, we’re all working toward, which is a better patient outcome. MGEN, for me, is one that has highlighted how I think this should be done.

[00:12:46] Obviously identified by clinicians in terms of treatment failures of their patients, identified by genomics in terms of these are the mutations that are causing the resistance. And then a partnership between the laboratory, the clinicians, and the commercial diagnostic company to deliver a better diagnostic option that enables new pathway for treatment of those patients.

[00:13:12] And then went on to inform guidelines. STI guidelines based on the work that we’ve done within MGEN, have been modified so that they recommend resistance guided therapy as the first path of treatment for anyone infected with M. genitalium, again shows people how they should be using the antibiotics. More focused, as opposed to just the syndromic approach where treat everybody the same and not based on the individual bacterial infection that they have. 

[00:13:41] Janet Silver: And beyond MGEN, I’m wondering is there enough control, is there enough technology? Do we have the resources to put those kinds of controls in place across the board, for all STIs?

[00:13:53] Colin Denver: I think that’s one of the things that, that obviously comes into how quickly you can get these options into the market and into routine use within a laboratory. As fast as you can develop a diagnostic kit, you also need to have the positive controls to ensure that the lab is able to deliver the consistent results that you need to consistently deliver the right information for treatment.

[00:14:16] So as quickly as you can work to develop both options. The diagnostic detection as well as the controls that the laboratory needs to utilize, and then as well as the quality control, or the quality assurance panels, that goes out to ensure that everybody’s able to deliver consistent results.

[00:14:33] I think that the quicker you can do that and the better alignment you have within all parts of that process, the better it will be for people, because we really don’t have a lot of time to figure this out. We have to build the plane on the way down.

[00:14:47] The resistance is popping up everywhere and it’s not getting better for sure. Now that we’re looking after covid, it’s actually getting much, much worse than we originally anticipated. 

[00:14:57] Cameron Groome: Take steady nerves to sew the parachute on the way down. 

[00:15:01] Colin Denver: Absolutely. 

[00:15:01] Cameron Groome: But I think your analogy is a great one, and we’ve got the same sort of, multiple drug resistance problems, STI infections across Canada. And that’s not just MGEN, but that’s chlamydia, that’s gonorrhea, syphilis, other STIs that I hope you’ve never heard of. 

[00:15:17] And maybe we could touch a little bit more on the way that MGEN resistance profile profiling changes the treatment protocols, Colin. 

[00:15:25] Colin Denver: Yeah. And again, it’s been a wonderful experience for SpeeDx in working with all of the sort of the key folks within that space.

[00:15:33] So again, when we started working with, originally with a group down in Melbourne, at Melbourne Sexual Health Center the cure rates for the MGEN infected patients were down as low as 48%. So, when you think about it, one of every two patients was failing frontline treatment. So, there’s a significant challenge that they had and a significant desire to adapt the current practice to something that they knew was going to be successful. 

[00:15:59] So we worked with them on a diagnostic strategy that changed the initial treatment from azithromycin to doxycycline, which is very effective at treating chlamydia, but not that great at treating M. genitalium. They would base the use of their azithromycin, so they did a sequential treatment pathway, where they would base the use of azithromycin on the results of the assay that we would run, which would tell them whether they were A, MGEN infected, and B, whether they had the resistance markers for azithromycin.

[00:16:28] And with that they were able to increase this as a study that was published in 2018, they were to see an increase in their curators of their patients using two very common antibiotics. So, doxycycline has been around for many years and still using azithromycin and moxifloxacin, which are well established antibiotics in the field. They’re able to increase their cure rates to over 95%. 

[00:16:51] So again, just by using the treatment options that we have available in a more focused, tailored, or personalized way, I think is really the way forward. 

[00:17:01] Janet Silver: Are you seeing, Colin, given what you have learned, are there key policy takeaways from this and how are you able to communicate what should be, perhaps the way forward and the standard forward to policy makers?

[00:17:15] Colin Denver: I think it’s a great point, Janet. And I think obviously you can create all these wonderful options that you like, but unless it’s been, I guess enabled by policy, it’s very difficult to change what the current practice is. And I think it goes to two main areas that I would say would influence that.

[00:17:32] So number one, clinical management guidelines. So, in our case it’s the STD management guidelines. So, we have guidelines based here in Australia, across Europe, UK, Canada, and the CDC guidelines in the US, have all changed to recommend this resistance guided therapy approach for things like MGEN, which is fantastic.

[00:17:53] The second aspect I would say is reimbursement. So, the laboratories that you want to run these assays, you want to be, and again, these assays are delivering significant both healthcare and economic benefits to wherever they’ve been implemented. You want to ensure that the laboratories are also incentivized to run these assays from a reimbursement point of view as well.

[00:18:17] So I think if you really combine those two elements, I think there’s a very good chance of quick and significant success. 

[00:18:24] Cameron Groome: So, Colin going from 10 patients out of 20 failing frontline therapy to one patient out of 20 is big. It’s just a huge advantage in better outcomes at a cost of maybe tens of dollars per patient versus, thousands or tens of thousands of more for complications.

[00:18:43] Is that a message that’s resonating with policy makers? Or is this still at the early days of understanding? 

[00:18:50] Colin Denver: I think it’s still probably early days. I think, obviously with the pandemic pause, as I would say, in terms of looking really at optimizing STD management, I think that a lot of the key studies that the policy makers would want to see in terms of healthcare economics just haven’t been performed when it comes to MGEN. But I think really you can focus on three main areas when you look at the benefits that are being delivered. And again, anything with antimicrobial resistance probably follows a similar path to what we see in MGEN.

[00:19:19] And, the three main areas, I would say the overall healthcare system, so both economics and the impact. The time you have antimicrobial resistance, you’re basically retreating the same infection, so your cost per infection, at least doubles. But again, if you’re re retreating them with the same antibiotic, it could triple or quadruple, depending on how many times you’re treating the same infection.

[00:19:40] Cameron Groome: And driving AMR.

[00:19:42] Colin Denver: But you’re also increasing transmission rates because people are not being cured the first time and they may think they are, and it’s spreading the infection or increasing the burden within the system. 

[00:19:52] Second one is on the clinicians. So obviously every time that you have to retreat the same infection, it increases the burden on the healthcare providers.

[00:20:00] And again, what we’ve seen over the course of the pandemic is that situation is something that we absolutely have to try to address in terms of maintaining high levels of capacity. Depending on what’s coming, whether it be winter or the next pandemic challenge, or whatever it might be. 

[00:20:16] But I think that the third one, and probably I would say the most important one is on the patient. So long term infection with some of these STDs can have really long-term effects on the person physiologically in terms of, could be infertility, could be chronic pain, things like that. But definitely from their mental health aspects. So, STDs really do have a significant impact on people’s outlook. And, the sooner you can clear them, the better it is for both their physiology and their mental health. 

[00:20:45] Janet Silver: Colin, just before we go off the top of this podcast, we said that SpeeDx was part of the AMR hub that was launched in August. What is the AMR hub? 

[00:20:54] Colin Denver: So, this is an Australian government funded collaboration between significant players within the STI research community here in Australia. And we do have some international participants as well. 

[00:21:05] But really, it’s asking the really hard questions within STIs, around AMR and how new pathways can be enabled to better address the significant challenges that we’ve talked about today. Getting to the last line of antibiotic treatment in gonorrhea or emerging resistance that we’re seeing in terms of MGEN or other STIs. So, it really brings together, I think, some of the key folks that we need to input on what’s next in terms of a better pathway to treat patients.

[00:21:35] So it’s a really exciting program and some really exciting things that are coming are, have already come out and are continuing to come out from the work that they do. 

[00:21:43] Cameron Groome: Thank you so much for this call and I’m excited about the prospect of, to see patients diagnosed, what’s the cause of the infection definitively? And then what’s an intelligently guided therapeutic regimen that treats the patient better, doesn’t propel AMR and gets more a cost-effective outcome. 

[00:22:03] Thank you and the whole SpeeDx team for such excellent work on this. And thank you so much for joining us today to inform us about it.

[00:22:11] Thanks, Janet. Thanks Cameron, for the opportunity to speak today. I really appreciate it. And yeah, I think, yeah, the way things are going the future isn’t as grim as it might look when you read the reports. I think there’s some really exciting research going on and we’re very pleased to be part of that process.

[00:22:27] Luck favors the prepared and the harder we work, the luckier we get. So, thank you again. That’s all the time we have for today, but thank you for tuning in. I’m Cameron Groome. 

[00:22:37] Janet Silver: And I’m Janet Silver, and this is Diagnostics Beyond the Lab. Till next time.

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