IGHID has a new hub of collaborative work focused on combating antimicrobial resistance (AMR). Leveraging the Institute’s pan-university framework, the program brings together expertise in basic science, pharmacology, epidemiology, clinical research and environmental studies from schools and departments all across UNC.
Led by David van Duin, MD, PhD, Gauri Rao, PharmD, MS, and Brian Conlon, PhD, collaborators are passionately pursuing a synergic approach that will make AMR research more effective, with a pathway for training. Following is a spotlight on the founders, who also include Jonathan Juliano, MD, MSPH, DTM&H, Tessa Andermann, MD, MPH, and Luther Bartelt, MD, DTM&H. Their first project is “The Program on Antimicrobial Resistance at UNC to Promote Scientific Excellence” (PAUSE), a finalist in this year’s Creativity Hub seed funding competition. This is an effort to determine the clinical impact and sources of relevant bacteria in order to optimize diagnosis and treatment approaches to AMR infections.
WHY IS AMR AN IMPORTANT ISSUE?
Conlon: “Antimicrobial resistance continues to rise while new drugs are slow to come to market. It’s been predicted that more deaths will be caused by AMR than cancer by 2050.”
Juliano: “Globally, AMR has become a critical problem with enormous public health impacts. In low resource setting in Africa where I work, the free access to antimicrobials has led to high rates of colonization with AMR bacteria and multi-drug resistant infection. Treatment options in these areas are limited for these organisms.”
Andermann: “Increasingly, patients are receiving treatments that result in significant immune compromise, putting them at risk for severe infections. Without effective antimicrobials, the risk of infection due to immunocompromising therapies such as organ transplantation, or intensive chemotherapy threatens to outweigh the benefits and safety of these treatments. AMR has enormous implications for how we currently treat cancer, rheumatologic diseases, and organ failure, among others.”
Van Duin: “Resistance to antibiotics is increasingly common in bacteria, viruses, and fungi that cause disease. The consequence of this concerning development is that patients who we as physicians would otherwise be able to treat quite easily with available antibiotics, may get delayed or less effective treatment of their infections.”
HOW IS THIS EFFORT ADDRESSING THE ISSUE AT UNC?
Van Duin: “In the last year or so, we have been bringing various experts together to facilitate AMR research. We have a specific focus on training the next generation of AMR researchers.”
Conlon: “We are creating key resources at UNC, including a clinical specimen biorepository that people across campus can use to address their AMR research questions.”
HOW IS IT BEING ADDRESSED GLOBALLY?
Juliano: “We have begun to invest in developing sequencing infrastructure at UNC Project Malawi. We have already conducted in-country sequencing of drug resistant E. coli isolates and are currently working on a study of neonatal sepsis.”
WHAT IS YOUR SPECIFIC ROLE AS AN AMR COLLABORATOR?
Van Duin: “I have been working with colleagues in different schools and departments at UNC, as well as with colleagues at NC State University and Duke University on collaborative ways to answer important questions in AMR. Within the Antibacterial Resistance Leadership Group (ARLG, administered through Duke University), I am the PI for the Multi-Drug Resistant Organism (MDRO) Network, which has enrolled over 7,000 patients internationally in clinical studies on the most important multi-drug resistant organisms.”
Conlon: “My research in microbiology and immunology focuses on antibiotic efficacy in the infection microenvironment, and my team is focused on creating new therapeutics that work with the immune system and antibiotics to clear infection.”
Juliano: “I am the former Medical Director for the Carolina Antimicrobial Stewardship Program at UNC Hospitals. During this time, my lab began to conduct molecular epidemiology research around AMR. Now, we help support trainees and faculty interested in AMR for conducting genomic studies to better understand AMR genes and transmission of highly resistant bacteria.”
Andermann: “I’m focused on how the dynamics of antimicrobial resistance genes in the gut microbiome impact infectious risk with multi-drug resistant pathogens. I view AMR within the context of complex microbial-host-environment interactions that impact human health and disease.”
Bartelt: “My laboratory focuses on the ways a variety of pathogens for this work. AMR bacteria, colonize and potentially invade through the intestinal tract. We use experimental models to determine how resident microbes in the intestine provide protection against these invading pathogens, and then investigate how exposure like specific antibiotics and dietary factors result in a loss of function of these otherwise protective microbes. We use our findings to then test pre-clinical interventions that could diminish susceptibility to AMR bacteria colonization, thus limiting infection with these difficult to treat pathogens.”
HOW DID YOU BECOME INTERESTED IN AMR?
Van Duin: “I was working as an infectious diseases physician at the Cleveland Clinic, when we started to see the first patients infected with carbapenem-resistant Klebsiella pneumoniae. This was a calamitous development as patients with these types of infections were essentially untreatable. We had to revert to using colistin – a drug mostly abandoned in the 1950’s for safety concerns and lack of efficacy – and other minimally effective antibiotics. Many patients died. This led to our initial clinical studies into treatment and outcomes of these types of infections.”
Conlon: “I began my PhD research on Staphylococcal biofilms and their recalcitrance. I have continued my career examining reasons that antibiotics fail against particular infections and trying to come up with better therapeutic approaches.”
Juliano: “As a junior faculty member, I became interested in AMR while working to build the stewardship program at UNC and directly observing the enormous impact these bacteria have on patient outcomes.”
Andermann: “My interest in AMR stems from my clinical practice, caring for immunocompromised patients with increasingly drug-resistant infections for which we have fewer and fewer treatment options. The reality of antimicrobial resistance is one that I struggle with every time I am in clinic or on service in the hospital.”
Bartelt: “In my clinical practice many of the patients I see in consultation are struggling with infections with very limited treatment options, and sometimes these infections are severe leading to hospitalization and critical care. When the opportunity to be involved with AMR-related research arose, I was eager to contribute.”
WHAT ARE SOME OF THE NEWEST DEVELOPMENTS?
Van Duin: “We are interested in the rapid spread of a specific type of multidrug resistant bacteria, the so-called ESBL-producing enterobacterales. In the US, these bacteria are more and more common, a development further enhanced by the recent COVID-19 pandemic. My group is now working on exploring reasons why these bacteria spread so easily in communities.”
Conlon: “We are finding numerous facets of the immune response create an environment that is not conducive to antibiotic efficacy. These include major components of the innate immune response, such as respiratory burst.”
Andermann: “With the rise in AMR, we are resorting to alternative therapies such as bacteriophage that had previously disappeared from Western Medicine 100 years ago with the advent of antibiotics. Bacteriophage target and kill specific bacteria that may be resistant to current antimicrobials and are increasingly being offered as an option for patients in select centers, including UNC Chapel Hill, with refractory infections. While the science behind these therapies is still under development, we are gaining experience in treating extremely drug resistant bacteria with bacteriophage on a case-by-case basis under research protocols.”
IS THERE A PARTICULAR ACHIEVEMENT THAT HAS BEEN MOST GRATIFYING TO YOU?
Van Duin: “In our studies on carbapenem-resistant bacteria, we were able to show that the use of newly developed antibiotics resulted in far fewer deaths when compared to traditionally used antibiotics. Being able to show this benefit and encourage the use of these agents has been most gratifying.”
Conlon: “Being named a Burroughs Wellcome Fund Investigator in 2020 was gratifying as it acknowledged the impactful, sometimes risky research we’re undertaking.”
Andermann: “Getting to work with my colleagues in AMR has been fun, creative, and quite gratifying!”
What is the best advice you’ve ever received?
Van Duin: “Skate to where the puck is going, not where it has been.” (Wayne Gretzky)
Conlon: It’s not about coming up with the right answer, it’s about coming up with the right question.
Andermann: “Wash your hands. Frequently.”
The Institute for Global Health & Infectious Diseases (IGHID) attracts people who are driven to make big change. From principal investigators and grant managers to regulatory specialists and study coordinators, everyone has an important role to play in what we do around the world. We are pleased to highlight the work of the people who proudly serve IGHID.