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.

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.

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.