A century ago, a severe bacterial infection was often a death sentence. With the advent of penicillin and the antibiotics that followed, such infections became eminently manageable, even routine. Today, though, with the rise of antimicrobial resistance, we are perilously close to returning to where we were 100 years ago.
I have a unique and uncomfortable perspective on the looming crisis of antimicrobial resistance. I am the chief technology officer SeLux Diagnostics, a startup focused on the rapid diagnosis of infectious diseases. And as I write this article, I am praying for my grandfather, who played a pivotal role raising me and is now fighting for his life against West Nile encephalitis. While intubated in one of the nation’s best intensive care units and beating the long odds against West Nile — never count out World War II veterans — he has been infected with methicillin-resistant Staphylococcus aureus (MRSA), which exists in most U.S. hospitals, and is now being given broad-spectrum antibiotics.
“Superbugs” that have evolved resistance to all known antimicrobials have now appeared across the globe, creating public health and national defense crises. In the U.S. alone, at least 2 million people each year contract infections that are resistant to antibiotics and antifungals, resulting in more 23,000 deaths. Experts predict that without a major change in today’s treatment paradigm, deaths from superbugs will surpass deaths from cancer by 2050.
For people with sepsis, a potentially deadly condition triggered by infection, antibiotics must be administered immediately: Every hour without effective antibiotics decreases the survival rate by 8%. Because drug-resistant bacteria are so common, treating sepsis requires using the best, most wide-acting broad-spectrum antibiotics.
Because each use of an antibiotic provides an opportunity for bacteria to evolve “survival of the fittest” mutations that confer antimicrobial resistance, routine use of broad-spectrum agents, the norm in all U.S. hospitals, all but ensures the future demise of antibiotics.
To eliminate the overuse of overly toxic broad-spectrum antimicrobials, we must maximize the speed with which precision therapies can be prescribed. Despite advances in personalized medicine in other areas of health care, using diagnostic testing to personalize antibiotic therapy still typically requires three or more days to complete.
This agonizing delay is most harmful for patients with superbugs that are resistant to standard broad-spectrum agents, many of whom die while their doctors are waiting for test results. In addition to creating a fertile ground for antimicrobial resistance, such overtreatment may also do harm, compromising kidney, liver, and auditory function, and eliminating normal gut bacteria.
Recognizing the importance of rapid diagnostics to combat the impending resistance crisis, the U.S. government has taken three important steps in the last decade to create incentives for developing new, transformative technologies: creating Medicare payment incentives, developing a sample bank of resistant organisms, and directly funding innovation in the space.
The Centers for Medicare and Medicaid Services has now mandated nationwide antimicrobial stewardship programs in all U.S. hospitals. CMS has further restructured payments for patients hospitalized with infectious diseases to provide incentives to give the best-in-class care that rapidly transitions patients out of the hospital.
In 2015, the FDA and the Centers for Disease Control and Prevention joined forces to create the Antibiotic Resistance Isolate Bank. This repository provides to all qualified researchers rare strains of multidrug-resistant bacteria and fungi that are essential for testing new diagnostics and drugs. By making these sparse samples available, the FDA and CDC leveled the playing field for all researchers and companies.
In 2010, the Department of Health and Human Services gave the Biomedical Advanced Research and Development Authority (BARDA) the task of addressing the increasingly prevalent public health threat of antimicrobial resistance. BARDA now directly funds a dozen or so companies developing antibiotics and diagnostics. My company is one of these.
This support for diagnostic innovation has spurred significant venture capital investment and produced a flurry of novel approaches for performing and acting on rapid diagnostics. The Pheno system developed by Accelerate Diagnostics, for example, uses powerful microscopy technology to provide information on appropriate antibiotic therapies faster than other available platforms. The FilmArray from BioFire uses cutting-edge genotypic technology to rapidly identify pathogens, in some cases directly from patient samples. At SeLux, we have developed a novel approach for determining personalized antibiotic therapy for patients, including those with superbug infections. Time is of the essence in this fight.
My grandfather’s hospital room is decorated with the artwork of his great-granddaughters. We can only hope that decades from now, when they need antibiotics, we will have created a world in which these drugs still work. Thanks to a flurry of innovation spurred by a combination of government action and venture investment, we may be on the right path.
Eric Stern, Ph.D. is the co-founder and chief technology officer of SeLux Diagnostics.