Host‐Directed Biomaterials for Combatting Bloodstream Infections: From Macrocyclic Peptides to Immune‐Activating Cell Backpacks

Abstract Bloodstream infections (BSI) are a leading cause of mortality and morbidity in both civilian and military populations. Immunocompromised patients in hospital settings are susceptible to nosocomial infections and subsequently complex disease states such as sepsis and shock. Similarly, civilians and service members wounded from insults such as penetrating wounds, burn, and blast suffer transient immune dysregulation and are thus susceptible to infections from various pathogens. The current standard of care to prevent severe disease arising from BSI in these scenarios is some combination of time‐consuming diagnosis, periodic monitoring to identify symptomology, and ultimately treatment using high doses of antimicrobial compounds. However, state‐of‐the‐art approaches to monitor and treat BSI are burdensome, untimely, and reactive. Shortcomings with current approaches demand alternative strategies to treat BSI early thus preventing more advanced disease states. This review paper summarizes recent progress in novel treatment strategies to manage BSI arising from both bacterial and fungal pathogens. These approaches include novel molecules to confer protection by supplementing host‐directed immunity using various therapeutic interventions. Specifically, novel peptide‐based compounds, engineered extracellular vesicles, and synthetic microparticles will be discussed.