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This review examines the applications of ASPs in sepsis treatment, highlights their role in improving patient outcomes, and addresses the challenges posed by multidrug-resistant organisms. The review begins by exploring the global AMR crisis and its implications for sepsis therapy and then evaluates the Surviving Sepsis Campaign\u2019s guidelines and their limitations in the context of growing AMR. The core principles of ASPs in sepsis treatment are also discussed. Data from international and Korean studies indicate that effective ASPs may improve patient outcomes; reduce the length of hospital stay; and reduce the incidence of antibiotic-associated adverse events, healthcare costs, and AMR. However, diagnostic delays, staffing shortages, and inconsistent ASP implementation remain significant barriers. Furthermore, robust evidence supporting the effectiveness of ASPs in various patient populations with sepsis is required. This review concludes with the future directions for integrating rapid diagnostics, individualized treatment planning, and informatics. 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