Understanding, identifying, and combating resistance mechanisms in infectious diseases

Antibiotics and vaccines have played an important role in extending our lifespan by an average of 25 years. However, we are on the verge of a post-antibiotic era. Identified as a public health crisis, antimicrobial resistance is an increasing threat to global health. There are few new novel antibiotics available for treatment due to a decrease in pharmaceutical companies invested in antibiotic discovery and development. In the U.S. alone, about 2,000,000 people are infected with drug-resistant bacteria and roughly 23,000 deaths occur as a result [1]. Dr. Warren Rose, Associate Professor of Pharmacy at University of Wisconsin-Madison School of Pharmacy—both a practicing pharmacist and researcher—is trying to solve the growing problem of antibiotic resistance in infectious diseases by identifying real issues seen in his patient care setting and studying potential solutions to those problems. His translational and clinical research actively looks at how antibiotic exposures and treatments lead to the development of resistance, identifies treatment strategies to prevent resistance development and spread, and directly applies his findings to patients.

With the rise of antibiotic over-prescribing and misuse in our healthcare system, previously simple infections and procedures may soon become life-threatening. Use of the wrong antibiotic can select for antibiotic resistance, which can rapidly spread locally and globally, especially in hospitals. This can lead to deaths, a rise of health care costs, and a depletion of resources. Dr. Rose and his team of laboratory and clinical research fellows, an international medical scholar, a medical microbiology and immunology graduate student, and two pharmacy students, collaborate with a diverse group that include investigators from UW-Madison, Marshfield Clinic, UC-San Diego, Universite of Poitiers France, University of Melbourne Australia, and University of the Western Cape South Africa. These institutions come together to address the global problem of antibiotic resistance, studying bacteria with new and interesting resistance mechanisms, and surveying antibiotic resistance and treatment to combat these dangerous pathogens. 

Current research includes:

  • Antibiotic Combination Therapy on the Development and Prevention of Resistance - Traditionally, most bacteria-related diseases are treated with only one antibiotic drug. However, many current drugs are now considered ineffective. In the lab, Dr. Rose and his team are working on multiple projects to identify how different combinations of antibiotics can be used to treat multi-drug resistance pathogens. These include older antibiotics that tend to be overlooked as viable options, as they were thought to be ineffective. Their research includes understanding the mechanisms involved in certain drug combinations, identifying which combinations are most effective against pathogens, and looking at how those drugs interact together to enhance that activity. In the lab, they perform an in-vitro assessment of antibiotics. Using pharmacodynamic modeling systems, they attempt to understand the dose-response relationship to antibiotics used both alone and in combination against drug-resistant organisms. Once they identify a mechanism, they put it into a simulated model of the human condition to get a better understanding of its activity. After enhancing the activity of more potent agents, they can use these effective drug combinations to treat patients and impact the whole patient population.
  • Identifying Biological Markers (biomarkers) and Patient Genetics - Dr. Rose and his team are taking the precision medicine approach to antibiotic drug resistance by focusing on the biomarkers associated with patient outcomes in antibiotic therapy. Previously, researchers have just looked at the organism and the antibiotic, discluding the important role of the host. Each patient responds differently to antibiotics, so identifying biomarkers can be used to more precisely select antibiotics for patients at high risk of poor outcomes (mortality or duration of infection)  in serious infections. Dr. Rose and his team look at a possible dysfunction in the host that either changes their immune system or prevents their immune response from operating optimally. To prevent antibiotic failure, they can select more potent drugs for patients that are at high risk of resistant bacteria. They’re currently designing a clinical study, and have already identified biomarkers in patients that are at risk of a poor outcome.
  • Local and Global Antibiotic Resistance Surveillance - Infectious diseases are a worldwide problem. Dr. Rose and University of Wisconsin-Madison (UW) have collaborated with University of Western Cape, South Africa (UWC) to perform a comparative health systems analysis. The projects focus on antibiotic resistance assessments in high-resource and low-resource settings, targeting antibiotic resistance reduction and creating a quality improvement process in the hospital. Dr. Rose and his team partnered with UWC to tackle multiple antibiotic problems in various settings. Currently, their primary focus is on C. difficile, an infectious organism considered an urgent public health threat by the Center of Disease Control. Easily transmitted from patient-to-patient, people struggle with this infection throughout the world. After receiving antibiotics, patients with this organism often get antibiotic-related diarrhea, and complications may include death, colonic disruptions, and inflamed organs in need of removal. Dr. Rose and his collaborators are trying to understand the risk factors involved and identify how to prevent them in patients on an international level. They are continuing this research in the U.S. and South Africa, planning to reach out to other communities in UW’s Global Health Institute. They want to partner with other institutions throughout the world and continue to understand and identify solutions for global infectious disease issues. 

Growing up in a small town, Dr. Warren Rose recognized the constant need for healthcare providers in small communities, and the prominent role local pharmacy played in an overall community. With the knowledge that he could make a big difference in peoples' lives, he pursued a career in healthcare. The only healthcare provider in his family, Dr. Rose earned his PharmD from Butler University, completed his residency training in pharmacy practice at Rush University Medical Center, and finished a postdoctoral fellowship in infectious disease pharmacotherapy at the Anti-Infective Research Laboratory at Wayne State University. With his background as a practicing pharmacist in the hospital and clinic setting, Dr. Rose sees firsthand the problems that antibiotic over-prescribing and misuse place on our healthcare system. 

It was during his clinical pharmacy training that Dr. Rose became interested in research. He appreciated the basic and clinical investigation required for novel approaches to treating complex diseases. More fascinating than the diagnostic aspects of drugs, he was interested in pharmacology; how drugs affect the body and the associated responses. There's a balance between prescribing the appropriate therapy and overusing a certain treatment, which drives unnecessary resistance. Dr. Rose witnesses this fight against evolution actively in the lab; if an organism is exposed to an antibiotic, it will evolve and eventually overcome that antibiotic. The challenge to stay one step ahead of resistant microbes, find better antibiotic treatment options for patients, and assist other healthcare providers with tools to improve their antibiotic use motivates Dr. Rose to continue his work. 

When he's not in the lab or attending to patients, Dr. Rose enjoys the outdoors, whether he’s hiking, trail running, or fishing. He also enjoys spending time with his two young children, who keep him very busy.