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.