CURRENT PERSPECTIVES ON SEPSIS AND BLOODSTREAM INFECTIONS: EPIDEMIOLOGY, PATHOPHYSIOLOGY, DIAGNOSTIC ADVANCES, PHARMACOTHERAPEUTIC STRATEGIES, ANTIMICROBIAL STEWARDSHIP AND FUTURE DIRECTIONS

Abstract

Background: Sepsis is a life-threatening clinical syndrome caused by a dysregulated host response to infection resulting in organ dysfunction. Bloodstream infections are important contributors to sepsis and may rapidly progress to severe systemic inflammation, organ dysfunction, and septic shock. Despite advances in antimicrobial therapy and critical care, delayed diagnosis, antimicrobial resistance, altered pharmacokinetics, and biological heterogeneity continue to complicate the management of sepsis. Objective: This review summarizes current evidence on the epidemiology, etiology, pathophysiology, clinical manifestations, diagnostic approaches, pharmacotherapeutic management, antimicrobial resistance, antimicrobial stewardship, and emerging therapeutic strategies in sepsis and bloodstream infections. Methods: A narrative literature review was conducted using PubMed/MEDLINE, Google Scholar, Scopus, ScienceDirect, and the Cochrane Library. Literature published primarily between 2015 and 2025 was considered, with selected landmark studies and guidelines published before 2015 included where relevant. Peer-reviewed studies, clinical guidelines, randomized controlled trials, cohort studies, systematic reviews, meta-analyses, and relevant narrative reviews addressing sepsis and its pharmacotherapeutic management were considered. Results: Contemporary management of sepsis involves early recognition, appropriate empirical antimicrobial therapy, microbiological investigation, source control, fluid resuscitation, vasopressor support when required, and individualized antimicrobial dosing. Antimicrobial resistance has increasingly complicated empirical treatment and highlights the importance of antimicrobial stewardship, pharmacokinetic/pharmacodynamic optimization, therapeutic drug monitoring, and timely de-escalation. Emerging approaches include biomarker-guided management, immune phenotyping, endothelial and glycocalyx protection, microbiome-directed strategies, and artificial intelligence-assisted prediction. Conclusion: Effective management of sepsis requires an integrated and individualized approach combining rapid diagnosis, appropriate antimicrobial therapy, hemodynamic stabilization, source control, antimicrobial stewardship, and multidisciplinary critical care. Future research should focus on precision medicine approaches that account for the biological heterogeneity of sepsis and enable individualized therapeutic decision-making.