The issue of antibiotic resistance has been talked about for years—in the clinical lab, in hospitals and health systems, and in large forums with key players from around the world. Increasingly, it has become a matter of concern among the general public, as families and community circles have been impacted by extended lengths of stays in hospitals until the right antibiotic was prescribed. It’s a public health issue that has snowballed into a crisis that is now recognized internationally. Recent studies indicate that antimicrobial-resistant infections currently claim 50,000 lives each year across the United States and Europe alone, with many hundreds of thousands more dying in other areas of the world.
In the United States, $1 billion in federal investments has been set aside as part of the “National Action Plan for Combating Antibiotic-Resistant Bacteria” to fight drug-resistant infections with rapid diagnostics, surveillance, and accelerated discovery and development of new antibiotics. In September 2016, world leaders at the United Nations called rising antimicrobial resistance a fundamental threat to human health, development, and security. High rates of resistance have been observed globally in common bacteria (for example, Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus) that cause common healthcare-associated and community-acquired infections (urinary tract infections, wound infections, bloodstream infections, and pneumonia). The overuse of antibiotics is the single most important factor leading to antibiotic resistance.
A losing game of catch-up
If we look at how antibiotics have been developed over the years, innovation has often been reactive to a resistant strain or an ineffective drug. Since the earliest signs of resistance to penicillin, for example, we’ve seen many companies abandon the space as life-threatening infections have generally been overcome—and balance sheets have been limited. But in a 2013 report by the U.S. Centers for Disease Control and Prevention (CDC), Tom Frieden, MD, MPH, its former director, suggests what the true cost of this may be: “The loss of effective antibiotics will undermine our ability to fight infectious diseases and manage the infectious complications common in vulnerable patients undergoing chemotherapy for cancer, dialysis for renal failure, and surgery, especially organ transplantation, for which the ability to treat secondary infections is crucial.”1
In playing the game of catch-up, it’s nearly impossible to develop new antibiotics without making improvements to current diagnostics focused on tracking resistance. A 2013 Infectious Diseases Society of America (IDSA) policy paper stated that “Diagnostic tests play a major role in the clinical care of patients with infectious diseases, including detection of specific pathogens, discovery of new pathogens, determining appropriate therapy, monitoring response to therapy, assessing prognosis, and disease surveillance. Despite the increased use of rapid tests and the availability of molecular and proteomics-based tests, diagnostics are not being integrated into clinical care optimally.”2
The last two decades have witnessed the development of polymerase chain reaction (PCR) and other nucleic acid–based amplification technologies that detect microbial and genetic sequences with great sensitivity and specificity.2 PCR testing, the most widely used amplification method, wherein the tiniest amounts of DNA can be copied for analysis using a separate thermocycling machine, has shown great promise in infectious diseases, cancer, genetic diseases, histopathology, and other indications. Nucleic acid–based amplification technologies are used in molecular biology, and recombinant DNA technologies are now widely used in infectious disease diagnostics. The development of such technologies has given researchers and companies an opportunity to develop valuable and rapid diagnostics that play a critical role in the care of patients with and those at risk of developing an infectious disease.
Using the oncology playbook
In order to tackle antibiotic resistance, then, the infrastructure for supporting the development of diagnostics and therapeutics requires a facelift. A new approach is needed. Molecular diagnostics, as noted above, is part of the way forward. In addition, researchers and clinicians in infectious diseases can adapt the techniques of their counterparts in the cancer area, involving personalized medicine and powered by genetic testing. The oncology playbook can be used for infectious diseases.
Abandoning the one-size-fits-all approach, oncology companies are no longer playing a game of trial-and-error with approved medicines. Instead, they are applying genetic sequencing to identify mutations that are likely to cause a specific cancer, as opposed to the organ in which the cancer originates. This provides a more targeted approach to treating patients and increases the likelihood of a drug working.
Applying a similar approach to infectious diseases, companies leveraging the promise of genetic sequencing to power the development of rapid PCR-based diagnostics will be capable of producing a pathogen’s antibiotic resistance level in a matter of a few hours. When it comes to diagnosing patients with infectious diseases, timing is crucial to prevent the spread of the disease, properly treat the patient, and avoid unnecessary lengths of stay in the hospital.
To boost these efforts, we are starting to see the development of genomic databases of antibiotics and pathogens intended to help provide timely results on antibiotic susceptibility during the first examination in a hospital. The power of these sorts of databases is elevated with every patient sample, new or resistant antibiotic, and its resistance information. The hope is that clinicians will be able to utilize genetic tests with robust pathogen databases to treat patients, at the same time having an impact on the antibiotic resistance crisis.
REFERENCES
- Centers for Disease Control and Prevention. Antibiotic resistance threats in the United States, 2013. https://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf.
- Caliendo AM, Gilbert DN, Ginocchio CC, et al. Better tests, better care: improved diagnostics for infectious diseases. Clin Infect Dis. 2013;Dec 1;57(Suppl 3): S139–S170.
Evan Jones serves as Chairman and CEO of OpGen, provider of the Acuitas MDRO Gene Test and the Acuitas Lighthouse MDRO Management System. He also serves as a managing Member of jVen Capital, LLC, a life sciences investment company, and is a board member of Fluidigm, Inc., Foundation Medicine, Inc., and Veracyte, Inc.
