<p><strong>BACKGROUND: </strong>Fluoroquinolones (FQs) and extended-spectrum cephalosporins (ESCs) are associated with higher risk of Clostridioides difficile infection (CDI). Decreasing the unnecessary use of FQs and ESCs is a goal of antimicrobial stewardship. Understanding how prescribers perceive the risks and benefits of FQs and ESCs is needed.</p>

<p><strong>METHODS: </strong>We conducted interviews with clinicians from 4 hospitals. Interviews elicited respondent perceptions about the risk of ESCs, FQs, and CDI. Interviews were audio recorded, transcribed, and analyzed using a flexible coding approach.</p>

<p><strong>RESULTS: </strong>Interviews were conducted with 64 respondents (38 physicians, 7 nurses, 6 advance practice providers, and 13 pharmacists). ESCs and FQs were perceived to have many benefits, including infrequent dosing, breadth of coverage, and greater patient adherence after hospital discharge. Prescribers stated that it was easy to make decisions about these drugs, so they were especially appealing to use in the context of time pressures. They described having difficulty discontinuing these drugs when prescribed by others due to inertia and fear. Prescribers were skeptical about targeting specific drugs as a stewardship approach and felt that the risk of a negative outcome from under treatment of a suspected bacterial infection was a higher priority than the prevention of CDI.</p>

<p><strong>CONCLUSIONS: </strong>Prescribers in this study perceived many advantages to using ESCs and FQs, especially under conditions of time pressure and uncertainty. In making decisions about these drugs, prescribers balance risk and benefit, and they believed that the risk of CDI was acceptable in compared with the risk of undertreatment.</p>

<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>