Antimicrobial Treatment Duration in Sepsis and Serious Infections

Sepsis mortality has improved following advancements in early recognition and standardized management, including emphasis on early administration of appropriate antimicrobials. However, guidance regarding antimicrobial duration in sepsis is surprisingly limited. Decreased antibiotic exposure is associated with lower rates of de novo resistance development, Clostridioides difficile-associated disease, antibiotic-related toxicities, and health care costs. Consequently, data weighing safety versus adequacy of shorter treatment durations in sepsis would be beneficial. We provide a narrative review of evidence to guide antibiotic duration in sepsis. Evidence is significantly limited by noninferiority trial designs and exclusion of critically ill patients in many trials. Potential challenges to shorter antimicrobial duration in sepsis include inadequate source control, treatment of multidrug-resistant organisms, and pharmacokinetic alterations that predispose to inadequate antimicrobial levels. Additional studies specifically targeting patients with clinical indicators of sepsis are needed to guide measures to safely reduce antimicrobial exposure in this high-risk population while preserving clinical effectiveness.