From discovery to prevention to treatment, researchers at UNC-Chapel Hill are working to understand and mitigate the global rise of untreatable infections.
Nearly every one of us has had an ailment that was treated with an antibiotic. Think about what would happen if that treatment didn’t work. More than 2.8 million antimicrobial-resistant — or treatment-resistant — infections happen every year in the U.S., according to the Centers for Disease Control and Prevention.
These range from infections of the skin due to staphylococcus bacteria (staph), sexually transmitted infections like gonorrhea, and multiple illnesses caused by the Klebsiella pneumoniae bacteria, including pneumonia.
If an infection does not respond to existing medications, it can spread throughout the body. An international study from 2019 looked at the impact of antimicrobial resistance (AMR) in 204 countries and traced 5 million deaths to AMR-related health issues each year.
AMR mainly occurs when bacteria and viruses living in the body, on skin, and in the environment learn how to dodge antibiotics and antivirals. This impacts the entire health landscape. It causes infections that lead to hospitalization, can worsen the condition of someone already in the hospital, and can be fatal to people with compromised immune systems — children, seniors, people with cancer or organ transplants, and others.
“It’s a slow-moving catastrophe,” says David van Duin, professor of infectious diseases within the UNC School of Medicine (SOM). “People have just started to accept that AMR is getting worse, but it’s an existential threat to everything we do in medicine.”
Microorganisms that cause infection are changing faster than treatments can be developed. Some new antibiotics have been successfully created but it’s difficult and costly to do — and not the singular answer to combating AMR, says van Duin.
Slowing the creation
Solutions to these so-called “superbugs” will need a multidisciplinary approach because of their wide-reaching effects. Van Duin is part of an effort within the Institute for Global Health and Infectious Diseases to collaborate with researchers across the UNC-Chapel Hill campus to focus on key areas:
- providing new guidance on the use of antibiotics;
- reducing the spread of infections by developing better sanitation infrastructure and practicing personal hygiene;
- learning to better identify AMR to inform treatment; and
- developing new treatments and adapting current ones to be more effective.
Van Duin collaborates with the Antibacterial Resistance Leadership Group (ARLG) — a national network of researchers and caregivers — to combat AMR and improve patient care. Natalie Mackow, a third-year fellow in the Division of Infectious Diseases within SOM, is also conducting research with the group. Their goal is to investigate how AMR functions and educate health care workers on appropriately using antibiotics to stop the formation of more drug-resistant infections.
Mackow is starting a study that will examine the connection between AMR and antibiotic treatment in burn patients within the intensive care unit.
“Patients with extreme burns are more susceptible to infections in general because our skin protects us from infections,” she says. “AMR in these patients can lead to more surgeries, longer hospital stays, and higher mortality rates.”
While antimicrobial-resistant infections can develop in hospitalized patients, Mackow stresses that doesn’t mean the patient acquired the infection in the hospital.
Tracking the spread
Another way of combatting AMR is knowing where the most common — and dangerous — bugs are thriving. These infections can be tracked by methods like collecting hospital data and testing water supplies.
“Knowing what bacteria is present in a community and which antibiotics they respond to could help guide treatment when a patient from that community enters the hospital with an infection,” Mackow says.
Tracking also highlights disparities. Researchers have discovered that across all countries, AMR has a higher presence in areas with fewer resources.
Earth’s changing climate presents even more opportunities for AMR to grow and spread. Bacteria and viruses grow faster and stronger in warmer temperatures. And natural disasters lead to unsanitary conditions and increased pollution, exposing people to more potential superbugs. Tracking AMR after events like hurricanes or earthquakes presents another chance to gain insight.
Outsmarting the superbugs
When all else fails, including traditional antibiotics, new treatments are needed. That’s where Brian Conlon and his lab in the SOM Department of Microbiology and Immunology come in.
Conlon and his team focus on alternative strategies to treating infections with existing antibiotics. They aim to make previously ineffective treatments work better by manipulating how the treatment is delivered on a microbial level and reversing AMR by tricking the bacteria into responding to medication.
They’re also studying how diabetes, which affects more than one-tenth of the American population, impacts treatment.
“There’s evidence in mouse models that antibiotics are less effective when diabetes is present, which is concerning because diabetes is growing more prevalent in the U.S.,” Conlon says.
Looking to the future
Conlon’s goal is to find a way to completely clear a patient’s body of a drug-resistant pathogen, but with current treatments, he says that’s nearly impossible. Sometimes a person’s own immune system is to blame.
When the body fights an infection, it can force the superbug into hiding, making it more difficult for a drug to find, fight, and finish off the sickness. The immune system can even work against the drug itself. Conlon’s lab is experimenting with ways to make the battleground inside someone’s body more hospitable to treatment, which can be done by pairing an antibiotic with another drug.
These methods are promising, but need more investigation before they reach patients.
Conlon, Mackow, and van Duin’s efforts are examples of Carolina’s holistic approach to fighting AMR. Other aspects of this effort include research in basic microbiology, wastewater monitoring, drug discovery, infection prevention, and hospital epidemiology. And research on this subject continues to grow.
“We are grateful for support from the University, which helps bring together the AMR research being conducted by people across campus in different but related fields,” van Duin says. “True to the Carolina spirit, some of that work has global reach, while other components directly serve the interest of North Carolinians by investigating the state of the AMR crisis in our own communities.”
David van Duin is a professor in the Department of Medicine’s Division of Infectious Diseases within the UNC School of Medicine, founding director of the Immunocompromised Host Infectious Disease service within the school, and a member of the UNC Lineberger Comprehensive Cancer Center.
Natalie Mackow is an Antibacterial Resistance Leadership Group fellow and third-year fellow in the Department of Medicine’s Division of Infectious Diseases within the UNC School of Medicine.
Brian Conlon is an associate professor in the Department of Microbiology and Immunology within the UNC School of Medicine.