Antimicrobial resistance is a major global public health challenge, leading to increased morbidity, mortality, and healthcare costs. Antimicrobial Stewardship Programs (ASPs) are recognized as an effective strategy to improve the appropriate use of antimicrobials and to reduce the emergence of resistant microorganisms. However, despite national guidelines, many hospitals-especially in low- and middle-income settings-face important barriers to implementing and sustaining these programs.

The PeGASUS study is a nationwide, multicenter implementation initiative designed to support and strengthen ASPs in Brazilian public hospitals. The study will include approximately 54 hospitals across all five regions of Brazil that either do not have an ASP or have programs classified as inadequate or basic.

This is a pragmatic, quasi-experimental before-and-after study with historical control, conducted over approximately 21 months. The intervention combines multiple strategies to address common implementation barriers, including a structured web-based training program, engagement of hospital leadership, development of locally tailored ASP action plans, ongoing technical support, and collaborative learning between participating hospitals.

The study is organized into four phases: (1) pre-intervention (baseline), (2) intervention, (3) follow-up, and (4) wrapping up. During the baseline phase, data on hospital characteristics, antimicrobial use, and ASP organization are collected. During the intervention phase, hospitals receive training and support to implement ASP activities adapted to their local context. The follow-up phase evaluates the sustainability of the implemented strategies under routine conditions.

Outcomes include changes in the level of ASP implementation, antimicrobial consumption (measured as defined daily doses per 1,000 patient-days), number and acceptance of stewardship interventions, and clinical outcomes such as length of hospital stay and 30-day mortality. Additionally, a cost-effectiveness analysis will be conducted in a subset of hospitals.

All data are collected at the hospital level in aggregated form, without identifying individual patients, ensuring confidentiality and minimizing risks.

By combining capacity building, standardized tools, and continuous support, the PeGASUS study aims to bridge the gap between national antimicrobial stewardship guidelines and real-world practice. The findings are expected to provide evidence on scalable strategies to improve antimicrobial use and strengthen healthcare systems, particularly in resource-limited settings.

Inclusion Criteria:

• Public hospitals within the Brazilian Unified Health System (SUS)
• Presence of an established Hospital Infection Prevention and Control (IPC) committee
• Hospitals without an ASP or with an ASP classified as inadequate or basic, according to a standardized ASP assessment tool
• Availability of at least one infectious diseases physician (or physician with expertise in infectious diseases) or a clinical pharmacist with expertise in infectious diseases
• Presence of at least one adult intensive care unit (ICU), including medical, surgical, or coronary ICU
• Institutional agreement and commitment from hospital leadership to participate in the study

Exclusion Criteria:

• Hospitals without formal authorization or agreement from institutional leadership to participate in the study
• Hospitals with adult ICUs currently involved in other antimicrobial stewardship or infection-related intervention studies that could interfere with the outcomes