Antibacterial Resistance, Research, and Funding in 2024

Driving national progress to combat antibacterial resistance (AR) is a top priority for the Infectious Diseases Society of America (IDSA). AR has a significant and devasting impact on patient outcomes, and infectious diseases (ID) physicians are uniquely suited to lead the charge against AR. Created in 2013 and funded by the National Institute of Allergy and Infectious Diseases (NIAID), the Antibacterial Resistance Leadership Group (ARLG) includes experts in the field of AR. The ARLG plays an important role in the national AR strategy by prioritizing and accelerating research to support innovation and inform clinical practice and by recruiting and training the next generation of ID physician–scientists specializing in AR research.

Antibacterials are one of the most successful advances in human health, transforming medical care since their introduction into clinical practice in the 1940s. However, the concomitant development of resistance threatens human health given the significant role of antibiotics in modern medicine. Cancer chemotherapy, organ transplantation, complex surgeries, and biologics all carry a risk of infection and are made possible by the availability of safe and effective antibiotics. Secondary resistant infections complicate responses to pandemics and other public health emergencies. AR is referred to as a silent pandemic. Growing resistance and a weak antibiotic pipeline combine to create a bleak outlook, underscoring the urgent need for comprehensive solutions to optimize antibiotic use and develop novel antibiotics, both of which require an expert workforce.

The current pipeline has fewer than 50 antibacterial therapeutics in clinical development worldwide; only a handful target the most threatening gram-negative pathogens [1]. Small companies drive the vast majority of this innovation. The lack of investment in antibacterial development from large pharmaceutical companies leaves a significant void that requires federally supported intervention. The National Action Plan for Combating Antibiotic Resistant Bacteria (CARB) calls for federal agencies, including the National Institutes of Health, to facilitate the development of 10 novel therapeutics for bacterial infections in humans [2]. ARLG studies on new antibacterial therapeutic products and antibiotic development and ARLG collaborations with industry are important components of federally funded efforts. Key examples include the design of a customizable clinical platform trial to evaluate experimental antibacterial therapies for multidrug-resistant bacterial infections; an investigation of the safety and pharmacokinetics of ceftazidime/avibactam (AVYCAZ) combined with aztreonam (ATM), AVYCAZ alone, and ATM alone; and a prospective, multicenter, observational cohort study to provide data that will aid in the design of randomized clinical trials on therapeutics and diagnostics for carbapenem-resistant Enterobacterales infections.

It should be noted, however, that neither the ARLG nor the federal government is positioned to bring antibiotics to market, and novel financing mechanisms are needed to drive sustained private investment in antibiotic research and development. As such, the IDSA and more than 200 other organizations are calling for the US Congress to pass the bipartisan Pioneering Antimicrobial Subscriptions to End Upsurging Resistance Act, a bill that would create a subscription program in which federal government reimbursement for novel antibiotics would be delinked from their use to provide a predictable return on investment for antibiotics that aligns with appropriate use goals [3].

In addition to developing novel antibiotics, it is equally critical that we optimize use of existing and new antibiotics to improve patient outcomes and limit the development of resistance. As the federal government considers new investments to revitalize antibiotic research and development, it will be essential to safeguard those investments by preserving the efficacy of novel antibiotics developed with federal funds. Nationwide, 95% of hospitals report having implemented all 7 core elements of antimicrobial stewardship recommended by the Centers for Disease Control and Prevention (CDC) and required by the Joint Commission and Centers for Medicare and Medicaid Services [4]. However, persistent overuse and misuse of antibiotics remain significant challenges, recently exacerbated by the coronavirus disease 2019 pandemic [5]. This presents an opportunity for additional knowledge and tools to help guide appropriate antibiotic use.

The CDC supports important studies on broad antimicrobial stewardship interventions and provides tools to help prescribers apply research findings in real-world settings. Additionally, the Agency for Healthcare Research and Quality provides important funding to support implementation of antimicrobial stewardship. The ARLG makes unique contributions to research that inform optimal use of antibiotics, including strategy trials to optimize currently licensed antibacterials (eg, dose, duration, clinical algorithms, need for drug, combinations) in order to reduce the risk of resistance and validate new diagnostics. ARLG work on diagnostics for urinary tract infections; diagnostics for guiding use of new antibiotics, such as AVYCAZ and ceftolozane/tazobactam; and diagnostics for identifying susceptibility and resistance to carbapenems all provide clinically actionable information to help improve patient care and antibiotic use. These efforts have been important to the CARB National Action Plan objective for the federal government to support 10 new antibiotic resistance–related diagnostics projects.

Combating AR requires an expert workforce. While ID is a rewarding field with opportunities for physicians to positively impact patients and AR, recruitment has faced challenges. Given the disproportionate impact of IDs, including those caused by resistant pathogens, on communities of color and other marginalized communities, it is important to grow and diversify our field to better promote health equity. Limited funding opportunities for early-career ID physician–scientists pose a barrier to growing this workforce.

Additionally, multiple studies have demonstrated the impact of mentorship on success in academic medicine and ID specifically [6]. A 2016 survey of internal medicine residents found that among respondents who were interested in ID but did not apply to ID fellowships, 91% felt that mentorship was influential on career choice, but only 43% identified an ID mentor [7]. This indicates an opportunity to significantly enhance ID mentorship and thus grow and diversify our field. The ARLG provides several important mechanisms to support early-career ID physician–scientists focused on AR through funding and mentorship, including the John G. Bartlett ARLG Fellowship, Early Stage Investigator grants, and EVERYONE grants, specifically geared toward individuals from underrepresented populations.

As the NIAID budget has grown over time, so too has the amount of funding NIAID dedicates to antibiotic resistance, including the ARLG; however, the percentage of the NIAID budget that goes to the ARLG has in fact gone down. In fiscal year (FY) 2016 (the first year with total NIAID antibiotic resistance funding reported), the total NIAID budget was $4.629 billion, of which $413 million was dedicated to antibiotic resistance (8.9% of the total NIAID budget). In FY 2023, the total NIAID budget was $6.562 billion, of which $565 million was dedicated to antibiotic resistance (8.6%). The enormity and complexity of the antibiotic resistance crisis and its ability to undermine many of our most fundamental modern medical capacities underscore the importance of devoting far more federal resources to combating resistance. Conducting clinical trials is expensive, and additional resources would enable the NIAID and the ARLG to expand the antibiotic resistance research portfolio and increase funding and mentorship opportunities for early-career ID physician–scientists. The ARLG is uniquely valuable because it supports multisite studies worldwide to provide comprehensive data on antibiotic resistance, which are crucial to deepening our understanding of AR and fostering international partnerships to prevent the spread of resistance and advance scientific breakthroughs. However, such studies are costly to support and require additional resources.

We must effectively address AR to improve our preparedness for future emergencies and best leverage the latest scientific breakthroughs for patients. The ARLG will continue to play a vital role in these efforts.

Notes

Author contributions. A. J. and C. D. were responsible for drafting the manuscript and critical revision of the manuscript for important intellectual content.

Disclaimer. The content is solely the authors’ responsibility and does not necessarily represent the official views of the National Institutes of Health.

Financial support. Publication and administrative fees for this article were funded via Award Number UM1AI104681 from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.

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