Welcome to Molecular Ideas and thanks for sharing your time with us! Today, we sit down with the CEO of Astek Diagnostics to discuss his passion for solving the antibiotic resistance pandemic, especially when patients face the life-threatening condition, sepsis.
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It may be difficult to look at the COVID-19 pandemic and imagine that another challenge to collective medical challenge for humanity could exist in our lifetimes. We have declared war on cancer, developed vaccines with astonishing speed, and re-defined the limits of leadership when faced with enemies within. Unfortunately, there is another potential pandemic lurking in the shadows of COVID-19.
Something Resistant This Way Comes
We’ve known about antibiotic resistance for the better part of a century and have discussed it at length in our first Whitepaper. Antibiotics are traditionally small-molecule drugs that interact and interfere with bacteria through highly specific mechanisms of action (MOAs). Broadly speaking, antibiotics are used to treat bacterial infections by killing them outright (bactericidal activity) or by limiting their ability to proliferate further (bacteriostatic activity). In either case, antibiotics also grant the body’s immune system time to recognize the infection, develop antibodies against infection, and biochemically carpet-bomb the remaining bacteria.
Different Classes of Commercialized Antibiotics (organized by Year Introduced & MOA) | Data Source: Conly, J., & Johnston, B. (2005) & Lumen Learning
Antibiotics are a fantastic clinical tool to save lives and prevent the spread of disease – when they work. The abilities of a particular bacterium to grow, reproduce, and respond to its environment are governed by its genomic chromosome(s) and/or its extrachromosomal plasmids. Resistance to antibiotics arises naturally in a population when specific bacterium mutates (when precisely imperfect cellular machinery make copy errors in genomic material), or when one bacteria passes a bit of extrachromosomal genetic material (e.g., plasmids) to its peers via horizontal gene transfer. Bacterial mutations often tweak the targets of these highly-specific antibiotics so that they can’t interact.
These mutations differ from the standard ‘wild-type’ genetic profile of a population and are often a minority – until antibiotics wipe out the wild-type bacteria and leave the mutated ones behind. Even assuming patients fully follow the prescribed regimen of antibiotics (including after symptoms resolve), there is still a possibility that the mutated bacteria will survive and thrive.
Sepsis, The Archenemy
Managing the rise of antibiotic resistance is one of the most significant challenges in medicine today. When faced with a child’s ear infection, deciding whether to prescribe antibiotics – and which ones – is relatively simple. However, the decision gets considerably more complicated with life-and-death clinical scenarios like sepsis.
When bacteria enter the bloodstream, infections become serious. Bacterial metabolic activity can cause significant damage to organs around the body; more importantly, it can trigger an intense, widespread immune response that puts a patient’s life at risk. Separately, Acute Respiratory Distress Syndrome (ARDS), which is associated with countless COVID-19 deaths, is a complication of sepsis.
Treating sepsis almost always requires neutralizing the underlying infection. When caused by bacteria, this means that antibiotics are the first, second, and last line of defense. However, clinical science cannot be a trial-and-error game; using the right antibiotics means the difference between life and death. For every hour that goes by without the right treatment, a sepsis patient’s mortality risk increases by approximately 8.0%. Looking outward, hospitalizations from sepsis cost the U.S. healthcare system $41.8 billion in 2018, and may be responsible for as many as one in five deaths worldwide.
Know Your Enemy
Mutations can arise in a matter of seconds. Horizontal gene transfer can be facilitated in a lab within a matter of minutes. However, drug development takes years. We may not have a therapeutic substitute for antibiotics yet – but better information at the point-of-care is a good starting point. That’s why I was honored to sit down with Mustafa Al-Adhami, PhD, founder and CEO of Astek Diagnostics.
The first thing you notice on the company website is their aptly written tagline pertaining to antibiotics: “Underuse is a death sentence. / Overuse is a crisis.” Obtaining this information in high-pressure clinics is no mean feat. The current standard for identifying the antimicrobial resistance profile of bacteria is a culture test. These typically take 24-48 hours – far too long for a patient in crisis.
The company’s technology is designed to separate bacteria from blood and then identify their antibiotic resistance profile in well under an hour. Doing so with both speed and accuracy is challenging. Simply put, blood is complicated. While primarily composed of water, we’ve got white blood cells, red blood cells, platelets, free-circulating genetic material, and all manner of smaller biochemicals. While separating these components with traditional equipment is relatively simple, it takes time and bulky equipment that slows down the diagnostic process.
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When Art Inspires Science
Mustafa credits three sources of inspiration for Astek’s technology: mosquitos, Khal Drogo (from Game of Thrones), and his wife.
After being repeatedly bitten by mosquitos on holiday with his in-laws, Mustafa decided to spend the rest of his vacation learning how to replicate the method by which mosquitos isolated hemoglobin from the rest of blood (i.e., plasma). From there, he chose to pursue a Ph.D. at the University of Maryland to learn how to replicate that process in a device for the isolation of bacteria. Their device completes this stage within 25 minutes, isolating the bacteria-laden plasma from the rest of the heavier substances in the blood.
The second step is determining the right antibiotics that are needed to counteract the bacterial infection. This ‘identification’ stage is the second source of innovation. While traditional culture tests look for turbidity (‘cloudiness’) of a sample to test for the presence of bacteria, this doesn’t enable us to understand their metabolism. Using the special properties of a dye called resazurin (which fluoresces when NAD+ is converted to NADH during cellular metabolism), bacterial growth can be monitored in the presence of one of ten different antibiotics. From there, the software identifies which antibiotics a given bacteria is susceptible to, enabling a smarter, faster recommendation.
While sepsis may be prevalent around the world, it’s not a commonly recognized medical term. The award-winning book series and TV show Game of Thrones highlighted the effects of this disease through the arc of the much beloved character Khal Drogo (played by Jason Momoa). The barbaric warlord challenges an insubordinate tribe member to a duel. Despite his victory, he sustains wounds that become infected and lead to a terminal case of sepsis. While growing up in Iraq had left Mustafa as no stranger to hardship at the hands of unchecked bacterial infections, the character’s plot helped clarify which indication to which he would begin applying this technology.
Selling In
Unfortunately, science is not immune from salesmanship. Just having a technically better solution does not convince hospitals to adopt it. “I’m told I’m wrong so often,” says Mustafa “but the important thing is to bring excellent data and find your champions.” While pre-commercial, the team recognizes that navigating the hospital procurement and clinical implementation processes are tricky needles to thread. That said, they’re critical to ensuring data can be generated for clinical trials and for setting the groundwork for future clients once the diagnostic clears FDA approval. Part of the trick is to understand the relevant priorities of each team and committee, and tailor your pitch accordingly. As it stands, the device is on track for submission to the FDA along the Class III (de novo) classification in late 2023.
Potential Advocates for Antimicrobial Stewardship in Hospitals
However, pitching is not for the faint of heart. As a non-native English speaker and fellow introvert, Mustafa saw the presentation process as a significant barrier to launching Astek Diagnostics. His ‘break’ came when he was invited to present at the Three-Minute Thesis competition – the night before, at 10:00 PM. Mustafa was kind enough to share the details of how he approached this challenge with only hours to spare: he asked his wife for help, and they refined his pitch until the early hours of the morning. The next day, he was awarded the top prize.
That was a major turning point, and the path led to Mustafa applying for other competitions to raise funding and awareness. “Every time I could see how I'm improving, and I started getting into it. The UMBC graduate school had me apply to a competition in Maryland, which sent me on to the Southern states regionals. I won that and they sent me to national and I won national. And I was like, ‘This is crazy.’ I was not expecting this. I’m just a shy guy who barely speaks English.”
While the prizes for early-stage business competitions won’t power a medical device to market, they are critical for raising awareness, boosting confidence, and getting the critical feedback needed to jumpstart a venture.
Looking Behind Us and Ahead
Mustafa’s story crystalizes several pieces of wisdom for any aspiring entrepreneur. Life science companies are inherently complicated, and their competitive advantage is rooted in the expertise of their teams. However, expertise is not always derived from best practices or established insights. Mustafa’s relentless curiosity and observations around nature’s solutions to his technical challenges are what allowed him to form a simple, yet powerful solution to a global unmet need. Further, knowing one’s own weaknesses is essential – but actively seeking opportunities to surmount them is the first step to leaping into the future you want to create.
It’s clear that the antibiotic resistance threat will continue to plague humanity. In lieu of a new therapeutic modality and economic model for treating bacterial infections, we can be smarter, faster, and more judicious about how we use antibiotics.
Funding Note: Astek Diagnostics is currently in a seed extension round. If you are interested in learning more and/or participating, please reach out to Mustafa and his team at mustafa@astekdx.com.
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