ARLG investigator, Executive Committee Member, and Innovations Working Group Chair, Helen Boucher, MD, FACP, FIDSA, spoke with Contagion about current challenges and progress in combatting antimicrobial resistance (AMR). She sat for the video interview after delivering her Maxwell Finland Lecture,  “Running to Stand Still: Progress and Perils with AMR” at IDWeek 2022. “It [AMR] affects every one of us—you, me, our children—and I think it’s still not really understood and really embraced by many as a problem that affects them today,” says Dr. Boucher. Limited awareness about AMR, lack of antibiotics, and a gap in surveillance data to understand the extent of AMR in the United States are some of her primary concerns.

However, Dr. Boucher says she is encouraged by the progress being made to address AMR. The AMR Action Fund, a public-private collaboration, is investing $1 billion dollars to develop two to four new antibiotics by 2030. She also points out that 2019 CDC data shows infection prevention and stewardship have led to a decrease in some areas of resistance in hospitals.

Watch Dr. Boucher’s 2-minute interview on the Contagion Live website.

It’s that time of year again! Many of ARLG’s top leaders and experts will be at IDWeek 2022 discussing the latest AMR topics. Whether you are attending virtually or in person, plan ahead to join your favorite sessions.

Be sure you catch this year’s Maxwell Finland Lecture delivered by ARLG primary investigator, Helen Boucher, MD, FACP, FIDSA, on October 20. Use the guide below to find more exciting sessions and posters you won’t want to miss.

Learn more and view OnDemand content at IDWeek.org

IDWeek 2022 ARLG Sessions

IDWeek 2022 ARLG Posters

ARLG’s Desirability of Outcome Ranking (DOOR) is a novel paradigm for the design, analysis, and interpretation of clinical trials that allows doctors to create better treatment strategies by giving them a way to review data and compare the risks and benefits of different interventional options. Doctors can then discuss the pros and cons for each option and tailor the strategy to fit the patient.

Scott Evans, PhD, developed this innovative paradigm with support from members of ARLG’s Statistical and Data Management Center (SDMC) Toshimitsu (Toshi) Hamasaki, Lauren Komarow, and Carol Hill. The goal of DOOR is to give doctors and researchers a method for informed therapeutic selection based on a comprehensive patient-centric benefit-risk evaluation. Researchers can apply DOOR’s paradigm to the design, data monitoring, and analyses of any clinical trial or observational study to evaluate the patient experience and guide therapeutic decision-making.

ARLG researchers first used DOOR in clinical studies for antimicrobial resistance, but now teams are benefitting by applying DOOR to studies in other disease areas such as COVID-19, tuberculosis, melioidosis, pulmonary artery disease, stroke prevention, status epilepticus, and maternal-fetal medicine.

Building a DOOR to Better Treatment Strategies

For doctors, the most important “real world” application of clinical trial data is to determine which therapeutic option is best for each patient. However, since randomized trial outcomes do not provide a clear way to review and compare data on patient-reported experiences, they often fail to provide the necessary evidence to inform day-to-day medical decision-making.

DOOR helps improve the real world applications of clinical trial data by correcting the usual arithmetic of analyzing outcomes separately. Instead of using patients to analyze outcomes, DOOR uses outcomes to analyze patient experiences.

DOOR bases therapeutic evaluations on a comprehensive assessment of patient-centric benefits and harms, which helps doctors address the most important clinical questions on the comparative value of interventions as they pertain to specific patients.

By providing a way to transcend this obstacle, DOOR advances the goal for more research studies yielding practical data doctors and patients can use to answer real world questions.

A DOOR for More Streamlined Study Data

ARLG researchers have used DOOR to enhance many completed studies.

• CRACKLE I Study — illustrated that ceftazidime-avibactam was superior to colistin in the treatment of pneumoniae carbapenemase–producing CRE infections based on benefit-risk evaluations.
• PROVIDE Study — illustrated that higher vancomycin doses, presumed to be more efficacious were not more efficacious and caused more acute kidney injury than lower doses in hospitalized patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia.
• SCOUT-CAP Trial — concluded that among children responding to initial treatment for outpatient CAP, a 5-day antibiotic strategy was superior to a 10-day strategy.
• TRAP Trial — compared azithromycin treatment vs. placebo in outpatient adults with suspected lower respiratory tract infections and low procalcitonin levels.

Some current studies that incorporate DOOR include:

• Dalbavancin as an option for treatment of aureus bacteremia (DOTS) clinical trial — a multicenter, randomized, assessor-blinded, superiority trial comparing two doses of dalbavancin with 4–8 weeks of standard intravenous antibiotic therapy for completion of therapy in patients with diagnosed with complicated S. aureus bacteremia, including definite or possible right-sided infective endocarditis, who have been treated with effective antibiotic therapy and with subsequent clearance of bacteremia prior to randomization to study treatment.
• ARLG’s PHAGE Trial — a multi-center, randomized, double-blind, placebo-controlled trial of bacteriophage therapy in cystic fibrosis patients colonized with pseudomonas aeruginosa. DOOR is currently being used for the design, data monitoring and analysis of the study.

Through the DOOR: the Future of Trial Data

Although DOOR is already improving clinical trial conduction and the usability of data today, the paradigm has the potential to influence and advance the execution of research well into the future.  The Council for International Organizations of Medical Sciences is planning the release of a report on benefit-risk evaluation with recommendations that include DOOR concepts.

In order to improve access to DOOR, members of the ARLG team are currently building a series of interactive online tools that will help doctors and researchers easily conduct DOOR analyses and review the results. They are also developing similar tools that will help analyze the desirability of outcome ranking for the management of antimicrobial therapy (DOOR MAT) which is an analogue to DOOR for the design and analysis of diagnostic studies.

Keri Baum
Clinical Trials Project Leader II
Duke Clinical Research Institute (DCRI)

About my role in the ARLG DEI Working Group

I am a clinical trial leader who also supports the ARLG Diversity, Equity, and Inclusion (DEI) Working Group. My role in the working group is to implement efforts that fulfill our operational goal to facilitate the inclusion of underrepresented minorities in our research studies. We also seek the inclusion of diverse representation across the ARLG and the clinical trial teams we partner with.

In my role as an operational representative, I work to reinforce the importance of ethical clinical research practices in all stages of the project lifecycle, from planning to execution, participate in literature reviews, and develop and implement tools to be used at the operational level. This includes identifying sites that are successful at enrolling across demographics and leveraging bi-directional feedback so we can learn from their experience and expertise. I also partner with our statistical teams to measure our operational achievements and identify ongoing opportunities to include ALL patients who are afflicted with antibiotic resistance.

What is the ARLG DEI Working Group and what is its primary goal?

The Diversity, Equity and Inclusion Working Group is part of the ARLG Scientific Leadership Core (SLC). It was created to develop a framework to ensure implementation and full integration of principles of DEI throughout the Antibacterial Resistance Leadership Group.

We work to accomplish this goal by:

• Accessing, monitoring, and evaluating ARLG’s success in the current antibiotic resistance (AR) landscape
• Sharing educational and learning opportunities
• Promoting, mentoring, and developing investigator career advancement opportunities within infectious diseases (AR)
• Developing and maintaining an inclusive environment

Why is this work important?

 It is imperative that we make every effort to ensure that the data from current and future clinical trials is generalizable and an accurate reflection of the population that will benefit most from our studies. Knowing more about the people affected by AR advances the scientific validity and enriches the social and clinical importance of what we do.

In April 2022, the FDA released draft guidance on Diversity Plans to Improve Enrollment of Participants From Underrepresented Racial and Ethnic Populations in Clinical Trials. In this guidance, they highlight “representation in clinical trials and studies to be a priority.” It is reasonable to expect that there will be additional guidance and policies that encourage full implementation of DEI principles. ARLG has an actively engaged team of leaders and an operational support system that ensures we are well positioned to respond to these calls to action.

What do you like best about participating in the DEI working group?

When I first learned that ARLG was developing a DEI working group in 2020, I jumped at the opportunity to take part. My participation on this committee forces me to take a step back from my traditional, in the weeds, project operational role and look at the bigger picture.

This work has given me the opportunity to explore new ways to approach the systemic problem of underrepresentation at every level of research. Moreover, the information I have learned during my participation doesn’t stop at the research level. This acumen is applicable to many aspects of diversity, equity, and inclusion within our larger society. This knowledge and experience has reshaped my perspective in a way that will continue to positively impact my career for years to come.

In June, the Partnership to Fight Infectious Disease (PFID) featured a profile of ARLG fellow Tori Kinamon whose journey surviving a methicillin-resistant Staphylococcus aureus (MRSA) infection inspired her to pursue a career as an infectious diseases physician and researcher.

The profile is part of PFID’s Faces of AMR series, which strives to raise awareness of antimicrobial resistance (AMR) by sharing stories of people who have battled this public health threat.

Tori’s journey began during a gymnastics team competition when she was a freshman at Brown University. Her team won the championships, but in the days that followed Tori began to feel increasing pain and swelling in her left leg along with flu-like symptoms. A visit to the emergency room revealed an abscess in her hamstring that eventually required eight surgeries, more than a month in the hospital, and antibiotic treatment for a MRSA infection that almost necessitated the amputation of her leg.

After trying several antibiotic treatment options, doctors found one that was effective, but later discovered that Tori’s kidneys did not tolerate it well. Luckily, Tori’s hospital had another antibiotic option available, daptomycin, which treated her infection without affecting her kidneys.

“I reflect quite frequently on how having that one extra drug in the stockpile had a significant impact on my outcome,” Tori said.

Tori’ s experience with AMR fueled a passion to advance infectious diseases treatment and research. Today, she is an MD Candidate at the Duke University School of Medicine and a recipient of the FDA Antibacterial Drug Resistance (DOOR) Fellowship. Tori has contributed her insight previously to educational presentations and articles including a July 2021 WebMD feature along with Vance Fowler, MD regarding the effect of the COVID-19 pandemic on AMR.

Read Tori’s full story on PFID’s Faces of AMR here.

The International Society of Antimicrobial Chemotherapy (ISAC) announced it has selected Robin Patel to receive the 2022 Hamao Umezawa Memorial Award (HUMA). Dr. Patel serves as ARLG’s Laboratory Center Director and is the Director of the Infectious Diseases Research Laboratory at the Mayo Clinic.

Dr. Patel’s work focuses on developing improved diagnostic approaches to combat antibacterial resistance, researching the mechanisms of biofilm formation, and designing and conducting studies for new antibacterial treatment options. Her numerous career highlights include serving as president of the American Society for Microbiology, a council member for the National Institutes of Allergy and Infectious Diseases, and an associate editor for the Journal of Clinical Microbiology. She has published more than 500 peer-reviewed publications.

HUMA, which is ISAC’s highest award, recognizes outstanding contributions in the field of antimicrobial chemotherapy by a researcher, scientist, or clinician. Dr. Patel will receive her award medal, certificate, and 10,000 Swiss Francs during the 32^nd International Congress of Antimicrobial Chemotherapy (ICC 2022) scheduled for November 70 – 30 in Perth, Australia. She will deliver the HUMA plenary lecture on “Microbial Theranostics – A Resistance Combatting Strategy”.

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The U.S. Department of Veterans Affairs (VA) selected Robert Bonomo as the Director of the Coordinating Center for the VA Science and Health Initiative to Combat Infectious and Life-Threatening Diseases (VA SHIELD), a cental biospecimen and data repository.

Dr. Bonomo is Chief of the Medical Service and Director of the Geriatric Research Education and Clinical Center (GRECC) at the Cleveland VA Medical Center as well as a member of the ARLG Laboratory Center Consortium Team. His work in antibacterial resistance includes research on the mechanistic basis of resistance to beta-lactam antibiotics and beta-lactamase inhibitors, the molecular epidemiology of multidrug resistant Gram-negative bacteria, and the implementation of molecular diagnostics in clinical care of patients with infectious disease. Dr. Bonomo has received more than 70 honors and awards including the 2020 Mark Wolcott Award for Excellence in Clinical Leadership.

The VA SHIELD houses specimens and data related to COVID-19 and other emerging diseases to help VA investigators and other collaborators develop diagnostic, therapeutic, and preventative strategies for use in clinical care. The new initiative will support the VA’s national emergency preparedness efforts by helping to facilitate a faster, more coordinated response to emerging diseases.

“By understanding emerging disease data as it relates to large patient populations, VA can accelerate its research efforts to combat future outbreaks in a more coordinated, expedited fashion,” said Dr. Bonomo. “The Coordinating Center of VA SHIELD will be responsible for positioning VA to respond rapidly to national and international biological events and threats and to substantially contribute to clinical research and development”.

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