The Antibacterial Resistance Leadership Group: First Steps

The creation of the Antibacterial Resistance Leadership Group (ARLG) in 2013 signaled recognition by the National Institute of Allergy and Infectious Diseases that the public health crisis of antibiotic resistance had reached such severity that the nation needed a high-level team to devise a strategic clinical research agenda to tackle key scientific aspects of the problem in a well-coordinated manner. This approach followed mounting scientific evidence of the worsening crisis of antibiotic resistance; robust discussion among scientists, physicians, policymakers, and other leaders and experts about the solutions needed; and nearly a decade’s worth of advocacy by the Infectious Diseases Society of America (IDSA) for US federal leadership on this issue. Following the creation of the ARLG and other high-level projects and programs to address antibiotic resistance from various angles, the US federal government launched the 2014 National Action Plan on Combating Antibiotic-Resistant Bacteria (CARB) [1] and the corresponding National Action Plan [2] to guide a well-coordinated and robust response. As federal agencies and nongovernment stakeholders—including physicians, scientists, healthcare facilities, pharmaceutical and diagnostic companies, public health entities, patients, advocates, and others—work to meet the important goals and objectives set forth in the National Action Plan, we will need a strong foundation of research to support, inform, and evaluate our efforts. The ARLG is an example of a successful public–private partnership that has driven research on the wide array of issues related to antibiotic resistance, and it is well positioned to continue playing a critical role in the United States and through global collaborations with other groups.

As the Centers for Medicare and Medicaid Services move to require all acute care hospitals and long-term care facilities to implement antibiotic stewardship programs [3], infectious diseases physicians, policymakers, and others will be seeking data to inform their implementation. A study in progress supported by the ARLG that compares the effectiveness of 2 interventions (formulary restriction and preauthorization vs prospective audit) on targeted antibiotic use in community hospitals [4] is a prime example of the types of studies that are needed to optimize stewardship interventions. Similarly, ARLG-supported studies on oral step-down therapies for complicated urinary tract infections [5] and Staphylococcus aureus bacteremia [6] and on shorter-course therapy for pediatric pneumonia [4] can help modify and strengthen treatment protocols for those diagnoses to better align with stewardship principles.

Closely related to stewardship, the ARLG has also prioritized diagnostics studies. New diagnostics—including rapid, point-of-care tests and tests that can identify an infecting pathogen and its resistance—are critical for stewardship because they will inform effective treatment strategies. The ARLG has not only supported specific studies for rapid diagnostic tests for highly resistant, life-threatening pathogens, but has also created an online biorepository of well-characterized clinical isolates collected from ARLG studies. This biorepository (https://arlgcatalogue.org) can be a valuable resource for an even broader array of scientists conducting diagnostics research for whom access to clinical isolates for test validation is often burdensome or cost-prohibitive. New diagnostics are also critical for identifying patients who are eligible for new antibiotic studies—another chief priority for the ARLG. In addition to supporting the research and development of new diagnostics, it is equally important to give clinicians the tools necessary to optimize use of existing diagnostics. Outcomes studies are crucial to help clinicians understand the impact a diagnostic test can have on a patient’s care, and the ARLG-supported study on the effect of 2 rapid diagnostics for gram-negative bacteria on patient outcomes [7] is a key example of the type of study that is needed.

While the United States is poised to make significant advancements related to antibiotic stewardship that aim to slow the development of resistance, we cannot completely stop resistance from occurring or spreading. We urgently need new antibiotics and novel treatment strategies to treat patients infected with multidrug-resistant bacteria today and a robust pipeline to meet threats that will emerge tomorrow. The ARLG is undertaking various studies focused on developing new treatments for pathogens for which there is considerable unmet medical need. This contribution is vital, particularly given the persistent dearth of pharmaceutical company presence in this area. Physicians eager to see new treatments reach the market continue to hope that the strong foundation laid by the ARLG through projects like the platform trial design for antibacterials and novel endpoint studies will combine with robust economic and regulatory incentives being considered in the US Congress [8–10] to make antibiotic research and development more feasible and attractive for companies.

The ARLG is also contributing to the development of the next generation of infectious diseases physician-scientists with a fellowship opportunity for infectious diseases fellows. At a time when relatively fewer and fewer young physicians are applying to infectious diseases training [11] and fewer young people are pursuing research careers across disciplines [12], the ARLG is providing an opportunity for stimulating, fully funded research on one of the most pressing topics in medicine. The IDSA has identified the need for strong mentorship opportunities and access to research funding as critical elements of securing a pipeline of future infectious diseases physician-scientists who will be needed to devise solutions, and implement them, for antibiotic resistance and other infectious diseases threats.

The ARLG can continue to have a significant impact in our nation’s broader effort to address antibiotic resistance. While progress has been made, we are only in year 2 of the CARB 5-year National Action Plan [2], and much more work remains to (1) optimally implement stewardship programs and other initiatives to prevent infections and limit the development of resistance across the health care continuum; (2) stimulate research and development of urgently needed antibiotics, diagnostics, vaccines, and alternative therapeutics; and (3) strengthen surveillance and data collection of antimicrobial resistance patterns and antibiotic use. In addition, the recent United Nations focus on antimicrobial resistance underscores the importance of global collaboration in research. Strategically designed clinical research, such as the studies supported by the ARLG, will continue to catalyze and inform this important work.

Notes

Supplement sponsorship. This article appears as part of the supplement “Antibacterial Resistance Leadership Group (ARLG): Productivity and Innovation,” sponsored by the Antibacterial Resistance Leadership Group.

Potential conflicts of interest. B. E. M. has received personal fees from AstraZeneca, Cempra, Paratek Pharmaceuticals, Back Bay Life Science Advisors, the University of Texas Medical School at Houston, and UpToDate, and grants from Forest/Actavis, Cubist/Merck, and Theravance. A. J. reports no potential conflicts. Both authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.