Antibiotic stewardship—the coordinated effort to optimize antimicrobial use—is integral to hospital medicine, though its origins extend much earlier than contemporary clinical programs suggest.1,2 The initial recognition of antibiotic resistance occurred shortly after penicillin’s widespread use began in the 1940s.3,4 British bacteriologist Mary Barber documented hospital-wide outbreaks of penicillin-resistant Staphylococcus aureus in 1947, tracing transmission through hospital staff and implementing hygiene and antibiotic monitoring interventions that significantly reduced resistance rates within a decade.4-6 Concurrently, Alexander Fleming, who discovered penicillin, issued a prescient warning in his 1945 Nobel lecture about antibiotic misuse potentially leading to resistance, laying a conceptual foundation for future stewardship programs.3
Despite these early warnings, antibiotic use surged in hospitals during the 1950s and 1960s, resulting in escalating hospital-acquired infections involving resistant strains.6,7 This prompted calls for systematic approaches. In 1981, clinician-scientist Stuart B. Levy founded the Alliance for the Prudent Use of Antibiotics at Tufts University, advocating globally for cautious antibiotic usage.6 The Alliance for the Prudent Use of Antibiotics evolved into a significant educational and advocacy body, later merging with the International Society of Antimicrobial Chemotherapy in 2019. The term “antimicrobial stewardship” first appeared in literature in 1996, describing a strategic approach beyond mere reduction of antibiotic volumes, emphasizing correct drug choice, dosage, duration, and route.1,2,6
Throughout the early 2000s, awareness grew within the infectious disease and hospital medicine communities, driven by evidence revealing that 20% to 50% of antibiotic prescriptions in U.S. hospitals were either unnecessary or suboptimal, with adverse events affecting up to 20% of inpatients receiving antibiotic therapy.2,8 Responding to this crisis, the U.S. Centers for Disease Control and Prevention (CDC) launched its first educational initiative promoting stewardship in acute care hospitals in 2009, subsequently identifying improved antibiotic use as one of four national strategies to combat antimicrobial resistance by 2013.9 The CDC introduced its “Core Elements of Hospital Antibiotic Stewardship Programs” in 2014, outlining essential components including leadership commitment, accountability, drug expertise, action, tracking, reporting, and education.10,11 By 2015, the U.S. National Action Plan for Combating Antibiotic-Resistant Bacteria set implementation of these Core Elements in all federally funded hospitals as a key objective.
Between 2015 and 2020, regulatory and accreditation mandates reinforced stewardship initiatives. The Joint Commission recommended that all accredited hospitals establish active stewardship programs with clearly defined roles and protocols in 2017, followed by Centers for Medicare and Medicaid Services regulations mandating antimicrobial stewardship programs for all U.S. hospitals by March 2020.12 These regulations accelerated program adoption, with over 85% of U.S. hospitals reporting implementation of all seven Core Elements by 2020, up from 41% in 2014. However, the quality and effectiveness of these programs vary, particularly in resource-limited settings where robust implementation may be incomplete.
Modern hospital stewardship programs include diverse organizational structures and interventions. Hospitals designate physician and pharmacist leaders responsible for program outcomes, resource allocation, and accountability. 2,10,13 Infectious-disease pharmacists provide essential expertise, conducting prescription reviews, optimizing doses, and overseeing preauthorization systems.1,2 Core interventions commonly involve preauthorization processes requiring approval before administering certain antibiotics and prospective audits with feedback to evaluate and adjust antibiotic orders post-initiation. 1,2,8 Stewardship programs track metrics such as days of therapy, guideline adherence, and resistance patterns, providing detailed reports to clinical staff and hospital leadership.10,11 Continuous education is key, with training regularly delivered to prescribers and clinical staff on appropriate antibiotic use.10,13 Hospitals also implement evidence-based clinical guidelines tailored to local antimicrobial resistance profiles and formulary considerations, addressing common infections like pneumonia, urinary tract infections, Clostridioides difficile, and surgical prophylaxis.1,2
Hospital antibiotic stewardship programs demonstrate tangible clinical outcomes, reducing treatment failures, C. difficile infections, antibiotic-related adverse events, and hospital stays, while lowering costs.8,14 These programs can also contribute to slowing the emergence of resistance in specific settings, such as reducing C. difficile or multidrug-resistant organism rates, though broader resistance trends are influenced by factors like community use and global spread.14 For example, the multi-hospital Centralized Health System Antimicrobial Stewardship Efforts, or CHASE, stewardship network between 2018 and 2020 reported a 16% reduction in antimicrobial usage.15
Despite these advances, challenges persist. Antibiotic overuse remains a concern; a JAMA study from 2006 to 2012 across over 300 U.S. hospitals found no significant decline in overall antibiotic consumption, with increased use of broad-spectrum antibiotics like third- and fourth-generation cephalosporins.16 While more recent data suggest modest declines in hospital antibiotic use since 2012, inappropriate prescribing remains prevalent.17 Behavioral resistance among clinicians, driven by diagnostic uncertainty or concern about patient outcomes, complicates stewardship implementation, particularly in acute conditions like sepsis. Experts like Brad Spellberg emphasize that stewardship alone cannot fully address antibiotic resistance without concurrent development of new antimicrobials, advocating for complementary conservation and innovation approaches.18
Hospital antibiotic stewardship integrates with global frameworks, notably the One Health approach, which addresses antimicrobial use and resistance across human, animal, and environmental sectors. The World Health Organization’s AWaRe classification system, introduced in 2017, categorizes antibiotics into Access, Watch, and Reserve groups, guiding prescribing practices to limit resistance and preserve critical antibiotics globally.
Entering the 2020s, stewardship programs are widespread but unevenly implemented, particularly in smaller or rural hospitals needing tailored resources. The CDC supports these facilities through partnerships and specialized tools for critical access hospitals. Emerging research explores novel strategies, such as rapid diagnostics, clinical decision-support tools, and behavioral-economics-inspired “nudges,” and stewardship-focused care transitions.8
Antibiotic stewardship is essential to hospital-based patient care. Clinicians incorporate stewardship principles into daily decision-making, initiating timely empiric therapy and de-escalating based on diagnostic clarification. Pharmacists, microbiologists, and infection prevention specialists collaborate within multidisciplinary teams to audit usage, monitor trends, and provide feedback. Quality and patient safety leaders use stewardship metrics to monitor outcomes, adverse events, and guideline adherence. Hospital leadership plays a critical role in resourcing stewardship efforts, ensuring sustainability through reduced drug costs and improved outcomes. Documentation and validation remain crucial for maintaining CMS conditions of participation and Joint Commission accreditation. 2,10,12
In conclusion, antibiotic stewardship’s evolution—from early resistance recognition, through targeted advocacy, to standardized implementation—demonstrates its vital role in hospital medicine. Proven benefits include improved clinical outcomes, reduced adverse events, and sustained antibiotic effectiveness in specific contexts. Nonetheless, challenges such as clinician behavior, persistent inappropriate prescribing, the need for new antimicrobials, and implementation disparities necessitate continuous adaptation and support. Antibiotic stewardship remains an evolving, critical discipline safeguarding patient care and preserving the efficacy of these essential drugs for future generations.
Dr. Migliore
Dr. Migliore is an assistant professor of medicine at Columbia University College of Physicians and Surgeons and director of general perioperative medicine and consult services and medical director of surgery and surgical step-down at Columbia University Medical Center, both in New York.
References
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3. Fleming, A. Penicillin: Nobel lecture, December 11, 1945. Available at: The Nobel Prize website. https://www.nobelprize.org/uploads/2018/06/fleming-lecture.pdf. Accessed September 4, 2025.
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10. Centers for Disease Control and Prevention. Core elements of hospital antibiotic stewardship programs. CDC website. https://www.cdc.gov/antibiotic-use/hcp/core-elements/hospital.html. Published December 5, 2024. Accessed September 4, 2025.
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12. The Joint Commission. R3 report: issue 8: new antimicrobial stewardship standard. Joint Commission website. https://www.jointcommission.org/en-us/standards/r3-report/r3-report-8. Published October 19, 2016. Accessed September 4, 2025.
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17. Centers for Disease Control and Prevention. Antibiotic use and stewardship in the United States, 2024 update: progress and opportunities. CDC website. https://www.cdc.gov/antibiotic-use/hcp/data-research/stewardship-report.html. Published November 20, 2024. Accessed September 4, 2025.
18. Spellberg B, et al. The future of antibiotics and resistance. N Engl J Med. 2013;368(4):299-302. doi: 10.1056/NEJMp1215093.
