<p>Antibiotic-resistant bacteria infect 2 million Americans annually, resulting in up to 100,000 deaths and excess healthcare costs exceeding $20 billion. Antibiotic use is a major contributor to antibitotic resistance, <em>Clostridioides difficile</em> infections (CDI), and antibiotic-associated adverse events. Antibiotics are frequently used across all healtcare settings in the United States, although much of this use is unnecessary. In response, antibiotic stewardship programs (ASPs) have sought to coordinate efforts to improve antibiotic prescribing. Although there has been much progress with antibiotic stewardship (AS) over the past decade, gaps in optimizing the reach and effectiveness of AS remain. We convened a diverse, multidisciplinary group of AS clinicians and researchers to delineate and prioritize these research gaps from a US human health perspective.</p>

<p>We highlight 4 broad categories in which gaps exist (Table 1): (1) a scientifically rigorous evidence base to define optimal antibiotic prescribing practices, which adequately inform AS interventions across a variety of patient populations and settings; (2) effective AS approaches to recognize effective interventions, knowledge of how these interventions can be adapted for implementation both locally and across diverse settings, and an understanding of how interventions can be sustained once implemented; (3) standardized process and outcome metrics; and (4) advanced study designs with appropriate analytic methods, accompanied by infrastructure to support data collection and sharing.</p>

<p>Antimicrobial stewardship is pivotal to improving patient outcomes, reducing adverse events, decreasing healthcare costs, and preventing further emergence of antimicrobial resistance. In an era in which antimicrobial resistance is increasing, judicious antimicrobial use is the responsibility of every healthcare provider. Antimicrobial stewardship programs (ASPs) have made headway in improving antimicrobial prescribing using such "top-down" methods as formulary restriction and prospective audit with feedback; however, engagement of prescribers has not been fully explored. Strategies that include frontline prescribers and other unit-based healthcare providers have the potential to expand stewardship, both to augment existing centralized ASPs and to provide alternative approaches to perform stewardship at healthcare facilities with limited resources. This review discusses interventions focusing on antimicrobial prescribing at the point of prescription as well as a pilot project to engage unit-based healthcare providers in antimicrobial stewardship.</p>