Designing better systems to navigate the sepsis–antimicrobial stewardship tension

Sepsis is a leading cause of preventable death and requires timely antimicrobial treatment to reduce mortality. Despite extensive sepsis management guidelines, high-income countries continue to have considerable rates of sepsis mortality, indicating a gap between guideline quality, usability, and practical application. Simultaneously, the rise of antimicrobial resistance threatens the efficacy of antimicrobial therapies for infection control, underscoring the tension between sepsis management and antimicrobial stewardship. This Personal View explores how system factors, such as people, environments, tools, technologies, and tasks, influence the sepsis–antimicrobial stewardship tension. With the Systems Engineering Initiative for Patient Safety, we use a case study to highlight how organisational pressures, inadequate diagnostic tools, and sociocultural factors drive the gap between work-as-imagined and work-as-done. These latent safety risks that impede guideline adherence and contribute to unintended antimicrobial use highlight the need to design better systems, not blame individuals for non-compliance. We argue that addressing sepsis and antimicrobial resistance requires a holistic systems approach and that every discipline, including policy makers, clinicians, researchers, and drug developers, should adopt systems thinking in the design of interventions intended to address this problem. This shift is essential to ensuring effective care for patients today while safeguarding the effectiveness of antimicrobials tomorrow.