A primary goal of the ARLG is to train the next generation of researchers who will help reduce the public health threat of antibacterial resistance.
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Congratulations to the ARLG’s co-principal investigators, Vance Fowler, MD, MHS, Duke University, and Henry “Chip” Chambers, MD, UCSF, as well as a number of other ARLG investigators who have been recognized as world experts in Staphylococcus aureus by Expertcape.
In addition, Dr. Fowler was recognized as the number one world expert in bacteremia by Expertscape. Other ARLG leaders, such as Robert Bonomo, MD, David Paterson, MD, Ralph Corey, MD, and Tom Holland, MD, ranked high on the list.
Congratulations to Robert Bonomo, MD, ARLG Laboratory Center Co-Director, who was named a Distinguished University Professor at Case Western Reserve University (CWRU) during its fall convocation on August 28, 2019. CWRU awards the title of “Distinguished University Professor”— a permanent, honorific title, to acknowledge contributions of full-time, tenured faculty with exceptional records of research, scholarship, teaching, and service.
Bonomo, a professor of medicine, pharmacology, molecular biology, and microbiology at the CWRU School of Medicine, has dedicated his research career to addressing the mounting problem of antibiotic resistance. “Infections previously brought under control can resurface in resistant and more virulent new forms,” he said, “allowing disease to proliferate — potentially unchecked.”
Among his investigations, Bonomo works to uncover the genetic and amino acid determinants of bacterial enzymes that create multi-resistance to such widely used antibiotics as penicillins and cephalosporins. Nailing down these sequences and using an integrated approach can lead to new medications that overcome the antibiotic resistance, and his work is paying off. Because of his collaboration with colleagues at CWRU and elsewhere, five new antimicrobials have been approved to date. “We’re always trying to stay a step ahead of the bacteria,” he said. “Evolution rewards organisms that adapt to their environments, including those that fend off antibiotics, so there is a fundamental natural mechanism that we have to overcome.” Bonomo said his teaching and mentoring are as meaningful to him as his research. “Providing intellectual prep for the next generation helps ensure that future patients live longer, healthier lives,” he said. “Nothing can be more crucial than that.”
Read the complete article from CWRU.
Molecular diagnostic assays have transformed the field of infectious diseases, allowing for swift and sensitive detection of organisms previously challenging to diagnose, but it can be difficult to study how these new tests perform. Members of the Antibacterial Resistance Leadership Group (ARLG), which is facilitated by the Duke Clinical Research Institute, recently conducted a study of several assays used to detect Neisseria gonorrhea and Chlamydia trachomatis. They say their latest research will help to quell the transmission of these infections and could change the landscape for how diagnostic tests are studied.
Prior to this study, there were no diagnostic tests approved by the U.S. Food and Drug Administration (FDA) for determining the presence of extragenital gonorrhea, despite recommendations from the U.S. Centers for Disease Control and Prevention for screening in certain populations, said the DCRI’s Vance Fowler, MD, MHS, (pictured), co-principal investigator for the ARLG. As a result, few laboratories offered testing and clinicians lacked an FDA cleared diagnostic test. Lack of testing can result in the continued spread of the bacteria that cause chlamydial and gonorrheal infections, including infections from drug-resistant strains..
“Accurate diagnostics that are more readily available will result in better detection and timely treatment, which could help to slow the rise of antibiotic resistance,” Fowler said. “Diagnosis is a major problem in antibacterial resistance, and gonorrhea has been identified by the U.S. Centers for Disease Control and the World Health Organization as a concerning bacterium with rapidly emerging resistance.”
Investigators collaborated with the National Institute of Allergy and Infectious Diseases (NIAID), the FDA, Cepheid, and Hologic on this unique study design that incorporated simultaneous testing of samples from a single patient’s pharynx and rectum on multiple diagnostic platforms. Results from this simultaneous testing were incorporated into a reference, or gold standard, that could then be used to assess whether each of the diagnostic platforms correctly diagnosed extragenital gonorrhea and chlamydia.
After establishing the reference standard, the study team conducted a clinical trial that enrolled more than 2,500 patients. The study tested a new design that allowed evaluation of multiple diagnostics from different companies simultaneously. “This idea came from the work I do in my investigative lab, where we often reuse the same clinical samples to answer multiple questions,” Fowler said. “I began to realize that the same idea could be applied to evaluating new diagnostics — if we could test multiple diagnostics on the same patient enrolled into a single trial, we could potentially reduce costs associated with enrolling multiple patient cohorts. This is about enhancing pragmatism in the diagnostic space.”
In 2014, Fowler presented the concept of “one patient, more than one diagnostic” at a meeting sponsored by the National Institutes of Health. Evaluating diagnostics for extragenital gonorrhea was a way to test this strategy. Fowler relied on the sexually transmitted infection expertise of his ARLG colleague and primary investigator of the project, Jeffrey Klausner, MD, MPH, from the University of California-Los Angeles. On May 23, 2019, two of the devices evaluated in this study received FDA clearance for use to detect pharyngeal and rectal gonorrhea and C. trachomatis, the first two devices approved for this indication.
Fowler sees wide applications for the design and believes the same technique of testing multiple diagnostics simultaneously could be used in many other conditions, such as urinary tract infections, bloodstream infections, and pneumonia. This process could also benefit companies developing diagnostics in several ways. First, the cost of enrolling patients into a Master diagnostic trial would be only a fraction of the conventional approach. Next, each company would ultimately receive the trial data relevant to their platform along with the reference standard for submission to the FDA for clearance of their diagnostic platform.
“Employing a platform such as this could enhance and facilitate the ability to develop and ultimately commercialize new diagnostic platforms, providing clinicians with more informed decision making in managing patients with infections caused by multi-drug resistant bacteria,” Fowler said.
The ARLG develops, designs, implements, and manages a clinical research agenda to increase knowledge of antibacterial resistance. It aims to advance research by building transformational trials that will change clinical practice and reduce the impact of antibacterial resistance. The ARLG is facilitated by the DCRI and works under the centralized leadership of an executive committee and two principal investigators: Fowler and Henry ‘Chip’ Chambers, MD, of the University of California, San Francisco.
Other authors that collaborated on this study include Sarah Doernberg, MD,MAS, of the University of California-San Francisco.
Research reported in this article was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number UM1AI104681. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
The U.S.-based Antibacterial Resistance Leadership Group (ARLG), part of the Duke Clinical Research Institute (DCRI) and the University Medical Center (UMC) Utrecht, the managing entity of the COMBACTE (Combatting Bacterial Resistance in Europe) consortium, will work together to solidify a comprehensive global community to combat the threat of antibiotic resistance around the world.
This collaboration is expected to take several forms, including joint design and implementation of clinical research, working meetings at scientific conferences like the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), and IDWeek, cross-entity working groups with diverse functional group participation, clinical trial innovations, data and protocol exchanges, and, contractual, regulatory, and systems harmonization.
“We at the ARLG have long admired the work being done by COMBACTE to increase the efficacy of antimicrobial drug development,” said Vance Fowler, MD, an investigator at the DCRI and co-principal investigator of the ARLG. “Combining our efforts will allow us to maximize the work we both do to stop the advancement of antibacterial resistance.”
Both organizations have been working toward the same mission since each launched in 2013, and now, the two groups will share their work to increase synergy and avoid duplicative efforts in clinical research.
“We have already made efforts to expand our reach across Europe, where an increasing number of people suffer from infections caused by antibiotic-resistant bacteria,” said Marc Bonten, MD, coordinator of COMBACTE and a professor at UMC Utrecht. “But by collaborating and sharing our progress with the ARLG, we can make a truly global impact beyond this population — an important consideration in a globally connected era in which epidemics travel across oceans quickly.”
As part of the agreement, the ARLG will have the opportunity to lead and coordinate U.S.-based studies for all clinical research initiated by COMBACTE, while COMBACTE will have the opportunity to lead and coordinate ARLG-initiated projects in Europe.
The full release can be found here.
Support your ARLG colleagues who will be presenting at the 29th European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) in Amsterdam, Netherlands from April 13-16, 2019.
| Date/ Time | Session Title | Presenter (Chair or Moderator noted) | Topic (if presenter) | Place |
|---|---|---|---|---|
| Saturday, April 13 13:30 – 14:30 | Antibacterial activity of unusual combinations | Barry Kreiswirth | Multifactorial treatment approaches targeting carbapenem-resistant and hypervirulent Klebsiella pneumoniae | Arena 2 |
| Saturday, April 13 14:45 – 15:45 | Clinical Trials with recently approved or late- stage development antibiotics | Thomas Holland | An efficacy analysis by lesion size of iclaprim versus vancomcin in patients with acute bacterial skin and skin structure infections: pooled phase III REVIVE trials | Arena 5 |
| Saturday, April 13 14:45 – 15:45 | Beta-lactamase inhibitors: the “second generation” meets the “first generation” problems | Robert Bonomo | Imipenem-relebactam efficiently inhibits D179 variants of the KPC-2 beta-lactamase | Arena 2 |
| Saturday, April 13 10:00 – 12:00 |
Management of chronic bone and joint infections | Robin Patel (Chair) | Hall D | |
| Sunday, April 14 11:00 – 12:00 | Pathogenetic profiling to fight antimicrobial resistance | Robert Bonomo (Chair) | Hall K | |
| Sunday, April 14 14:45 – 15:45 | Antibodies in the flight against multidrug-resistant Gram-negative bacterial infection | Robert Bonomo (Chair) | Hall H | |
| Sunday, April 14 11:00 – 12:00 |
Possible impact of new immunomodulators on infection and infection management | David van Duin (Chair) | Hall B | |
| Sunday, April 14 14:45 – 15:45 |
US experiences | Bettina C. Fries | Antibody-mediated killing of multidrug-resistant Gram-negative bacteria: what’s the future? | Hall H |
| Monday, April 15 07:30 – 8:30 | How to use Point-of-Care tests in microbiology? European vs. | Robin Patel (Chair) | Robin Patel (Rochester, United States) | Hall J |
| Monday, April 15 16:00 – 18:00 | Phage therapy’s coming of age: Progress towards the application of bacteriophages in the treatment of infectious diseases | Robin Patel (Chair) | Hall J | |
| Tuesday, April 16 08:45 – 10:45 | MRSA, VRE and beyond | Cesar Arias (chair) | Hall H | |
| Tuesday, April 16 11:00 – 12:00 | Recent Clinical Trials | Vance Fowler | Exebacase (Lysin CF-301) Improved clinical responder rates in methicillin-resistant Staphylococcus aureus bacteraemia including endocarditis compared to standard of care antibiotics alone in a first-in patient phase 2 study | Hall N |
| Tuesday, April 16 11:00 – 12:00 |
Infection in immunocompromised hosts | David van Duin (Chair) | Hall J | |
| Tuesday, April 16 12:15 – 13:15 |
Networks for Clinical Research – no other way | David van Duin (Moderators) | Arena 4 | |
| Tuesday, April 16 12:15 – 13:15 |
Networks for Clinical Research – no other way | Sarah Doernberg | ARLG in the USA | Arena 4 |
| Tuesday, April 16 13:30 – 15:30 |
Interventions to reduce morbidity and mortality of bloodstream infection | Thomas Holland | Patients’ experiences with Staphylococcus aureus and Gram-negative rod bloodstream infections: a qualitative study to inform development of a quality of life measure | Hall N |
| Tuesday,April 16 13:30 – 15:30 | Bacterial resistance: evolution, plasmids and fitness | Barry Kreiswirth | Processes driving the evolution of antibiotic resistance | Hall E |
Congratulations to Michael Woodworth, MD, MSc, for being selected as a recipient of the Southern Society for Clinical Investigation (SSCI) Research Scholar Award. This award provides funding for physician-scientists with innovative research projects related to internal medicine and its subspecialties. Dr. Woodworth will use the award to provide additional project funding for the ARLG ongoing pilot clinical trial of fecal transplantation for MDRO eradication in renal transplant patients.
Members of the ARLG Multi-Drug Resistant Organism (MDRO) Network coordinating team are visiting sites around the world to assess training success in several regions and find ways to enhance partnerships and practices within the MDRO Network.
This Network is a global community of professionals with a common mission to participate in clinical trials that: 1) provide observational data to aid in the design of randomized clinical trials on therapeutics and diagnostics for MDRO infections; 2) develop new diagnostic and treatment paradigms; and 3) inform clinical practice that will improve the care and outcomes of patients with antimicrobial resistance around the world.
The MDRO Network has 57 sites in 11 countries. Under the oversight of MDRO Principal Investigator, David van Duin, MD, PhD, and in collaboration with regional leaders Cesar Arias, MD, PhD, David Paterson, MBBS, PhD, Minggui Wang, MD, Lead Clinical Research Associates (LCRAs) David Souto and Beth Evans conducted these site visits in accordance with the National Institutes of Health (NIH) regulatory compliance requirements. Souto traveled to Colombia and Argentina while Evans visited sites in China, Singapore, and Australia.
Evans stated, “Being able to connect with these regional centers and sites in person, gives us valuable information and shows us, that despite cultural and language differences, everyone involved contributes their best work to help with combating the global threat of antimicrobial resistance.”
While visiting these RCCs, RCLs, and sites, the ARLG/MDRO team members toured, reviewed, and observed various study related components, facilities, and processes. On occasion, the Lead CRA team member supported the RCC’s onsite efforts, and offered recommendations and re-trainings. These visits highlight the collaborative, bi-directional features of the Network and lay the groundwork for future trials.
MDRO coordinators also hosted regional training sessions during the site visits. These trainings gave members of the ARLG/MDRO coordinating team the opportunity to meet site study teams and other Network members, as well as, provide face-to-face information about study design, procedures, implementation, and clinical research best practices.
“These site visits have given us a great opportunity to get to know the people conducting studies around the world,” said Souto. “Having the opportunity to explain why this work is important and get to know the people at the regional centers has helped us to ensure dedicated engagement, as well as standardization, consistency and quality throughout the MDRO Network.”
We call on you to support the “Clinical Case Challenge” – an international challenge highlighting the value of in vitro diagnostics in the fight against AMR.
This challenge invites medical students, trainees, physicians and others worldwide to submit their case studies on this important healthcare topic, thereby increasing open access cases for medical education.
Many medical schools have gaps in clinical diagnostics and antimicrobial resistance (AMR) content. A challenge is proposed to solicit clinical diagnostic and AMR clinical cases through a global call for participation. Clinical diagnostics are tests to aid clinical management and/or guide treatment decisions. The purpose of the challenge is to encourage medical students, trainees, physicians, and others to collect or write clinical cases that could be used in medical education and shared online. The challenge has two types of clinical cases: original cases written specifically for the contest and not published before; adapted cases that have been published elsewhere and tailored for medical education use.
Guidelines for submissions are described below. The final deadline for cases is May 1st, 2018.
bioMérieux is proud to be the sole sponsor of this initiative developed by the International Diagnostics Center and the London School of Hygiene and Tropical Medicine, the main organizer of this contest. Send your clinical case!
Details: http://www.seshglobal.org/Clinical-Case-Challenge
Questions: Contact the challenge coordinator at AMRcasechallenge@gmail.com
IDSA congratulates the distinguished physicians and scientists from the United States and around the world who were elected this year to be Fellows of IDSA.
Fellowship in IDSA honors those who have achieved professional excellence and provided significant service to the profession. “There has never been a more critical nor more exciting time for the field of infectious diseases. From an emerging outbreak of Ebola in the Congo to domestic outbreaks of measles to working tirelessly to solve the mystery of the patients before them, infectious diseases doctors are on the front lines of research and clinical care, keeping us safe from dangerous illness,” said IDSA President Paul Auwaerter, MD, MBA, FIDSA. “The individuals receiving the FIDSA designation have demonstrated that they are true leaders—in their institutions, their communities, and in the field of infectious diseases.”
Check out the individuals who were honored as Fellows of IDSA.