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.

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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The launch of a new European clinical trial network in September will aid in the battle to combat antimicrobial resistance by delivering rapid, high quality research studies. The European Clinical Research Alliance for Infectious Diseases (ECRAID) features a coordinated, single-point-of-access model that aims to streamline infectious diseases research, reduce costs, and accelerate medical advancements.

The EU-funded ECRAID-Base project is supporting the ongoing development of ECRAID into an independent, self-sustaining, not-for-profit organization over the next five years.

ECRAID’s infrastructure combines networks built by the Platform for European Preparedness Against (Re-)emerging Epidemics (PREPARE) program and the Combatting Bacterial Resistance in Europe (COMBACTE) consortium. The ARLG and COMBACTE have been collaborative partners since 2019. Herman Goossens, who has been a proponent of improving European clinical trial efficiencies by increasing collaboration, is spearheading ECRAID’s vision by serving as its executive director and CEO.

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