Managing sepsis in the era of precision medicine: a narrative review

For decades, the management of sepsis has adopted protocolized care bundles. However, the plateau in global survival rates suggests that the "one-size-fits-all" paradigm exemplified by early goal-directed therapy has reached its limits. The physiological and biological heterogeneity of sepsis necessitates a fundamental shift toward precision medicine. This review examines the transition from empirical resuscitation to individualized care across four critical domains. First, fluid strategy is evolving from aggressive loading to dynamic stewardship. Current evidence favors balanced crystalloids over saline and advocates restrictive dosing guided by dynamic responsiveness indices and venous congestion assessments to prevent iatrogenic harm. Second, hemodynamic support is shifting toward a catecholamine‑sparing strategy. To mitigate the metabolic and immunologic toxicities of high-dose norepinephrine, multimodal vasopressors, such as vasopressin and angiotensin II, are used to target specific biological phenotypes, such as high-renin states. Third, antibiotic management balances rapid administration with rigorous stewardship through pharmacokinetic optimization, including continuous infusions, diagnostic pauses for stable patients, and short-course regimens. Finally, corticosteroid therapy is moving beyond universal debate toward targeted application. Emerging data support their use in specific responder phenotypes, notably severe community-acquired pneumonia and distinct transcriptomic endotypes. In conclusion, modern critical care is moving beyond rigid protocols toward a personalized framework. By integrating bedside biomarkers and clinical phenotypes, clinicians can deliver "the right drug, at the right dose, for the right patient," thereby optimizing outcomes in sepsis and septic shock.