Thomas Holland, MD, MSc

Thomas L. Holland, MD, MSc

Associate Professor

Department of Medicine, Division of Infectious Diseases

Duke University

 

 

 

 

 

About my role in ARLG

I joined the ARLG in a role that might be best described as an early-career trialist. Over the years, my role has grown and evolved as I have been involved in more studies and part of the Gram-positive committee. Two of these efforts are:

  1. A set of projects around Staphylococcus aureus bloodstream infections. These infections are common and potentially deadly, but few trials have been done to try to determine the best treatment strategies for them. The ARLG has developed novel endpoints that improve trial feasibility and interpretation, including the desirability of outcome ranking (DOOR) and partial credit methods. Developed from a clinician survey and a patient-centered quality of life endpoint, we will use these endpoints in an upcoming interventional trial to test new treatment strategies.
  2. The Prospective Observational Evaluation of the Association between Initial Vancomycin Exposure and Failure Rates among Adult Hospitalized Patients with MRSA Bloodstream Infections (PROVIDE) Study. I had the opportunity to work with Tom Lodise, PhD, on PROVIDE, which was recently published in Clinical Infectious Diseases. In this study of patients with methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections, we found that increased vancomycin doses were not associated with better outcomes, and in fact resulted in more toxicity in the form of acute kidney injury. Vancomycin is the most commonly administered antibiotic in U.S. hospitals. Results from this study will inform new vancomycin dosing guidelines that will have a meaningful impact on how this antibiotic is used.

Why is this research important?

These projects are both impactful as they change the way antibiotic-resistant infections are treated and studied. They are also studies that would not be carried out in an industry-sponsored model. The S. aureus trial design work will change how the ARLG and others design trials, which ultimately will enable the scientific community to advance our knowledge of these antibiotic-resistant infections.

How did funding and support from ARLG help propel your career?

There is no equivalent opportunity to get involved in the design and execution of multi-site clinical trials, particularly with the mandate to rethink and improve how we design these trials. I cannot imagine a better structure to learn how to ask and answer meaningful questions through clinical trials with antibiotic-resistant pathogens. My primary mentor has been Vance Fowler, MD, and I have benefited tremendously from his leadership of the ARLG. I’m biased, to be sure, but I think this is the ultimate training ground for an early-career investigator with an interest in clinical trials that can address the crisis of antibacterial resistance.

For individuals who are not familiar with ARLG, is there one piece of information that you would want them to know?

The ARLG is an organization that is dedicated, from top to bottom, to innovating and moving the science forward. We never lose sight of the fact that these are real pathogens that cause infections in real people, and you won’t find a more dedicated group of people, motivated by this opportunity to make things better for all our patients.