Beyond antimicrobials: a host-directed precision pharmacotherapy framework for septic shock

Despite progress in antibiotic therapy and supportive care, septic shock continues to pose a substantial mortality burden in intensive care units, highlighting persistent limitations in current pathogen-focused treatment approaches. A central issue is the heterogeneity of host immune responses to infection, manifesting as diverse clinical phenotypes—such as immunosuppression and hyperinflammation—that drive variability in outcomes. Thus, evolving the therapeutic paradigm from infection control alone to precise modulation of the host response represents a critical next step for improving prognosis. This perspective article scrutinizes an integrated precision medicine framework that combines multidimensional host endotyping, targeted therapeutic strategies, and real-time monitoring with dynamic feedback. We examine its scientific foundations, potential clinical applications, and implementation pathways, while addressing current challenges and future directions. The goal is to offer a structured perspective and actionable insights to advance individualized management of septic shock.