The Management of Neonatal Sepsis and Septic Shock

Purpose of Review Neonatal sepsis (NS) is a leading cause of morbidity and mortality, and its definition has undergone recent changes. Neonatal septic shock (NSS), its most severe evolution, presents a clinical challenge due to its subtle and nonspecific early presentation, which often overlaps with normal neonatal adaptation and non-infectious conditions. Several diagnostic and therapeutic strategies have been developed to address NS and NSS, and these approaches are extensively discussed in this review. Recent Findings Biomarkers such as C-reactive protein, procalcitonin, interleukin-6, presepsin, and neutrophil CD64 may support diagnosis and management, but all have limitations. Targeted neonatal echocardiography and point-of-care ultrasound can improve shock phenotyping and guide individualized resuscitation, while near-infrared spectroscopy offers complementary information on regional tissue oxygenation. Machine learning models show promising diagnostic performance, but external validation and implementation studies remain limited. Antimicrobial stewardship, smaller fluid boluses, and physiology-guided vasoactive support are increasingly emphasized. Adjunctive therapies remain largely investigational and prevention continues to be the most effective strategy. Summary The management of NS and NSS is evolving from protocol-driven care to individualized, multimodal assessment. Integrating clinical evaluation with biomarkers, imaging, microbiological testing, and risk stratification may improve early recognition and treatment. Future progress will depend on rigorous validation of precision tools, broader access to bedside technologies, and context-adapted implementation strategies.