The Dalbavancin as an Option for Treatment of Staphylococcus aureus Bacteremia (DOTS) Study has completed enrollment! Despite launching in the early days of the COVID-19 pandemic, the trial reached its goal of enrolling 200 participants with S. aureus bloodstream infections on time in July 2023.  

S. aureus can cause life-threatening, antibiotic-resistant infections that have limited treatment options. The standard treatment typically involves intravenous antibiotic therapy that lasts four to six weeks. This therapy usually requires a central IV catheter and can prolong a patient’s hospital stay or result in admission to a nursing facility for antibiotic administration. 

In contrast, dalbavancin is a long-acting lipoglycopeptide antibiotic that can be administered as two intravenous doses one week apart to provide systemic therapy for six weeks. This strategy eliminates the need for a centrally placed catheter or prolonged IV access for antibiotic administration. While dalbavancin is FDA-approved for the treatment of acute bacterial skin and skin structure infections, its safety and efficacy for the treatment of S. aureus bacteremia has not been rigorously evaluated. The aim of the DOTS study is to test the safety and efficacy of dalbavancin compared to the standard treatment for S. aureus bacteremia.  

Thomas Holland MD, Associate Professor, Duke University School of Medicine, is leading the study, which includes 23 participating sites in the U.S. and Canada.  

“We are thrilled to complete enrollment for the DOTS trial,” said Dr. Holland. “This milestone is a testament to the hard work and dedication of our collaborators at sites across the U.S. and Canada, all of whom conducted the trial in the midst of a pandemic. We anticipate that DOTS will have practice-changing results for the management of S. aureus bacteremia, and we  look forward to sharing the results with the clinical community.”  

Congratulations to ARLG Mentoring Committee Vice-Chair and former ARLG fellow, Michael Woodworth, MD, MSc, on receiving the Shanthi V. Sitaraman Silver Pear Mentoring Award for Research from the Emory University School of Medicine! This award honors Department of Medicine faculty members who have exhibited outstanding mentorship to early-career mentees during the previous year. Dr. Woodworth’s mentee, ARLG Early Faculty Seedling Award recipient Ahmed Babiker, nominated him for the award. During the selection process, the award committee evaluates nominees on a variety of mentoring criteria including the pursuit of teaching excellence, assistance with presentations, publications, and scholarships, and participation in charitable or service-related activities. 

Dr. Woodworth’s research focuses primarily on the use of microbiome therapeutics like fecal microbiota transplantation (FMT) for the eradication of intestinal multi-drug resistant organism (MDRO) colonization. His team conducts clinical research using metagenomic approaches to identify potential mechanisms of action of FMT and leverages population-level datasets to study clinical outcomes for MDRO infections. 

The Emory University School of Medicine presented the award to Dr. Woodworth during its annual Department of Medicine Honors and Awards Celebration on August 30. The event acknowledges and celebrates the exceptional efforts and achievements of the department’s faculty and staff within their respective divisions, as well as their valuable contributions to the School of Medicine and Emory University as a whole. 

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The University of Minnesota (UMN) has appointed Melinda Pettigrew as its new Dean of the School of Public Health. As a part of this new role, she will serve as the chief executive and chief academic officer.

Dr. Pettigrew is the Chair of the ARLG Diversity Working Group and a member of the Laboratory Center Consortium Team. Previously, she served as the interim Dean of the Yale School of Public Health (YSPH) where she is currently the Anna M. R. Lauder Professor of Epidemiology (Microbial Diseases) and the deputy dean of YSPH. Her research explores the effect of microbiome disruptions on antibacterial resistance and the risk for hospital-acquired infections.

The new appointment is the result of a highly competitive national candidate search and will begin in December 2023. Dr. Pettigrew’s leadership will help to advance the UMN School of Public Health’s goals to advance population health and health equity.

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A June Magnify Magazine article titled “A Fighting Chance Against Infection” featured a profile on Tori Kinamon, ARLG Innovations Working Group member and MD Candidate at the Duke University School of Medicine.

In the article, Kinamon, a former gymnast who acquired a severe Methicillin-resistant Staphylococcus aureus (MRSA) infection during her freshman year of college at Brown University, detailed how that traumatic experience changed her perspective and inspired her to pursue a career in medicine.

As a medical student at Duke, Kinamon reached out to ARLG co-principal investigator, renowned researcher in S. aureus, and Florence McAlister Distinguished Professor of Medicine Dr. Vance Fowler, expressing her interest in infectious diseases research.

Kinamon has since authored multiple publications for scientific journals, participated in an ARLG panel discussion and an infectious disease conference in Dublin, Ireland, and was recently selected for an FDA Antibacterial Drug Resistance (DOOR) Fellowship – a competitive opportunity offered through the Oak Ridge Institute for Science and Education (ORISE). The fellowship evaluates ordinal endpoints using ARLG’s Desirability of Outcome Ranking (DOOR) approach for anti-infective clinical trials. DOOR is an innovative approach used in clinical trials to evaluate the global benefits and risks of an intervention.

Kinamon’s personal experience with a drug-resistant infection motivates her commitment to a patient-centered approach to care and the development of innovative treatments and preventive measures, including an infection prevention protocol for athletes, aiming to reduce the risk of infections like MRSA in athletic settings.

Kinamon emphasizes the importance of antibacterial research and development in the face of increasing rates of antibacterial resistance. She credits her fortunate access to an effective treatment for the positive outcome of her infection and expresses a passionate desire to provide the same opportunities for patients in the future.

“I don’t want to look a patient in the eye, or their family in the eye, and tell them they have an infection that we can’t treat. I want patients to have the outcome I was lucky enough to have,” Kinamon said.

Read Kinamon’s full profile for Magnify Magazine here.

An article published in the March 2023 issue of JAMA, “As Superbugs Flourish, Bacteriophage Therapy Recaptures Researchers’ Interest,” features research and input from a variety of infectious diseases experts including commentary from ARLG’s Laboratory Center Director, Robin Patel, MD and ARLG investigator, Robert Schooley, MD. The article, which discusses the development of phage therapy from the 1915 discovery of bacteriophages to now, also references ARLG’s PHAGE Study and the ARLG Phage Taskforce report, “Considerations for the Use of Phage Therapy in Clinical Practice.”

The JAMA article details how the effectiveness of phages—bacteria-infecting viruses—has been questioned since penicillin was found to be a safe, effective treatment for bacterial infections. Since antimicrobial resistance continues to grow, phage therapy is gaining attention as a potential solution to drug-resistant bacterial infections. Between 2016 and 2017, the National Institutes of Health (NIH) quadrupled funding for phage research to $160 million.

When the NIH commissioned the ARLG Phage Taskforce to conduct its evidence review of literature on phage therapy, the final report found “severe gaps” in evidence to support its use in clinical settings. Similar to antibiotics, bacteriophages selectively infect and kill bacterial cells, but ARLG’s report shows the need for more studies to determine the safety and efficacy of phage therapy before physicians can routinely use it in clinical care.

JAMA interviewed Dr. Robin Patel, Director of the Infectious Diseases Research Laboratory at the Mayo Clinic, ARLG’s Laboratory Center Director, and senior author of ARLG’s report for her input. She stated, “There are still so many questions. As a scientist, that excites me—but as a clinician…we don’t have an answer to whether phage therapy works.”

The article covers the NIH’s effort to address questions about the viability of phage therapy as an alternative to antibiotics by funding multiple clinical trials to evaluate safety and effectiveness. It highlights the efforts of many researchers including Dr. Robert Schooley, Distinguished Professor of Medicine, Infectious Diseases at the University of California, San Diego (UCSD), co-founder of the UCSD Center for Innovative Phage Applications and Therapeutics (IPATH), and ARLG investigator. JAMA touches on Dr. Schooley’s work as the co-principal investigator for ARLG’s PHAGE Trial, which is currently enrolling participants to take part in research on intravenous phage therapy for adults with cystic fibrosis.

Read the full article in JAMA

An editorial titled “Confronting Antimicrobial Resistance Together” by Henry Chambers, MD, and Vance Fowler, MD, was published in the November issue of the American Journal of Physiology – Lung Cellular and Molecular Physiology. The article reinforces the theme of World Antimicrobial Awareness Week 2022, “Preventing Antimicrobial Resistance Together,” and emphasizes the importance of One Health, a unified, transdisciplinary approach that aims to improve health outcomes by recognizing the interconnectivity of humans, animals, and our shared environments.

Drs. Chambers and Fowler use the COVID-19 pandemic as a key example of the need for a One Health approach to antimicrobial resistance (AMR). In 2020, COVID-19 deaths surpassed the number of deaths caused by the “Big Three” infectious diseases: tuberculosis (TB), HIV-AIDS, and malaria. The authors discuss how progress in the prevention and treatment of these illnesses was disrupted by the pandemic, and suggest that COVID-19 likely exacerbated AMR. Prescribing of antibiotics to patients without a bacterial infection, increases in hospitalizations, and overwhelmed diagnostic laboratories, among other factors, potentially could lead to increased rates of AMR.

The year before COVID-19 emerged, AMR was associated with 4.95 million deaths worldwide, putting this public health concern on par with TB, HIV, and malaria, and potentially even greater. Both COVID-19 and AMR are systemic, global health problems, and many of the same interventions utilized for COVID-19 and other infectious diseases are also effective in addressing bacterial AMR. For example, vaccines to prevent respiratory illnesses like COVID-19 and the flu can reduce hospitalizations and the over-prescribing of antibiotics to treat viral illnesses.

In addition to the misuse of antibiotics in humans, the article points to agricultural use of antibiotics as an area of particular concern for AMR. Approximately 73% of antimicrobials sold globally are given at low doses to animals used for food, creating an ideal environment for the development of drug-resistant bacteria. Organisms carrying resistance genes could be transferred to humans through food chains, to the environment through animal waste, and to other human pathogens, potentially disrupting fragile ecosystems and harming human health. A One Health approach to preventing AMR is especially important as population growth increases our interactions with other humans and animals.

Read the article in the American Journal of Physiology – Lung Cellular and Molecular Physiology.

Heather A. King, Ph.D.
Research Health Scientist, Durham VA Health Care System, Health Services Research and Development, Center of Innovation to Accelerate Discovery and Practice Transformation (ADAPT)
Assistant Professor, Department of Population Health Sciences and Division of General Internal Medicine, Duke University School of Medicine

About my role in the ARLG

For more than six years, I have had the opportunity to lead several ARLG patient-reported quality-of-life (QoL) studies on bacterial infections alongside wonderful ARLG collaborators like Drs. Thomas Holland, Sarah Doernberg, and Jessica Howard-Anderson. I also feel privileged to be part of ARLG’s Innovations Working Group under the leadership of Dr. Helen Boucher and to be a member of the Health-Related Quality of Life (HRQoL) Task Force. In addition, I provide expertise on study design and methodology to our U.S. and global colleagues.

About my work on QoL studies

We began our research in bloodstream infection and have expanded our work to address patient-reported HRQoL and its measurement across four major infectious syndromes which include complicated urinary tract infection (cUTI), acute bacterial skin and skin structure infection (ABSSSI), hospital acquired/ventilator associated bacterial pneumonia (HABP/VABP), and complicated intraabdominal infection (cIAI).

Current achievements and goals for this research

In July 2021, we produced a publication on patient-reported HRQoL in Clinical Infectious Diseases called Patients’ Experiences With Staphylococcus aureus and Gram-negative Bacterial Bloodstream Infections: A Qualitative Descriptive Study and Concept Elicitation Phase To Inform Measurement of Patient-reported Quality of Life.

We first presented the work that led to this publication at the Academy Health Annual Research Meeting. The review committee selected the corresponding abstract for best poster for the patient-centered research theme and nominated it for the overall ARM best poster award. We also published a second paper in Open Forum Infectious Diseases, Patients’ Experiences With Staphylococcus aureus and Gram-Negative Bacterial Bloodstream Infections: Results From Cognitive Interviews to Inform Assessment of Health-Related Quality of Life.

As reported in this paper, we developed a customized survey based on well-established patient-reported outcome measures for bloodstream infections that captures what matters most to patients as they recover. I have consulted with colleagues in the U.S. and overseas to guide their use of the survey and our measurement strategy. In addition to informing our current work, the survey is now part of an ongoing U.S. clinical trial.

We are currently conducting four systematic reviews of health-related quality of life measurement in patients with cUTI, ABSSSI, HABP/VABP, and cIAI. We are also performing a syndrome-specific qualitative secondary analysis of patients’ bloodstream infection experiences. These papers in development, along with others, will comprise a supplement on the importance of listening to, learning from, and leveraging patients’ perspectives of their HRQoL to create patient-centered antibacterial trials. In addition, we are comparing patient and clinician perspectives of patient health-related quality of life in cUTI.

Why is this research important?

Engaging patients is crucial to developing treatments for bacterial infections. It is important to capture outcomes that reflect what matters most to patients as they recover.

Our work informs the measurement of patient-reported HRQoL in studies for new antibacterial agents. By incorporating these patient-reported outcome measures into clinical trials, we learn valuable information about the patients’ perspectives on the effects of an intervention including how it influences function across a variety of life domains.

What do you enjoy most about being part of the ARLG?

The network is a strong proponent of incorporating the patient perspective in research on bacterial infections and antibacterial resistance. I greatly appreciate the network’s leadership in the specific area of patient-reported health-related quality of life and its measurement. The research our team has conducted with the support of ARLG is both significant and innovative. I am also very thankful to Drs. Vance Fowler, Henry “Chip” Chambers, and the ARLG as a whole for providing valuable mentorship and great opportunities that have advanced my career as well as the science of antimicrobial resistance.