Early Empirical Use of Broad-Spectrum Antibiotics in Sepsis

Purpose of Review Early antibiotic administration is the cornerstone of sepsis treatment guidelines and quality measures. We summarize recent key literature on sepsis definitions and screening, time-to-antibiotics and outcomes, and dosing considerations. Recent Findings Current sepsis clinical criteria have limited utility for identifying patients who warrant urgent broad-spectrum antibiotics because they include a very heterogeneous population, including many patients later found to have non-infectious syndromes or mild transient illnesses. The best available evidence supports immediate antibiotic administration (within 1 h) for patients with septic shock. Many sepsis patients without shock likely benefit from early antibiotics as well, but further high-quality studies are needed to precisely delineate the magnitude of benefit among potential subgroups and the time windows beyond which delays lead to worse outcomes. Time from antibiotic order-to-infusion and the order of antibiotic administration (i.e., beta-lactam before vancomycin) are two additional care processes found to be associated with outcomes. Empiric antibiotic choices should be informed by patients' likely site of infection, prior microbiology, comorbidities, severity of illness, and allergy profiles, and the development of better antibiotic resistance predictive models and novel rapid antimicrobial susceptibility testing hold promise for mitigating risks of both inadequate and unnecessarily broad antibiotic therapy. Lastly, incorporating established pharmacokinetic and pharmacodynamic principles, including aggressive loading doses and prolonged beta-lactam infusions, is critical to optimize clinical outcomes. A systematic approach to deciding who needs early versus immediate antibiotics, which agents to choose, and how to properly dose them may improve sepsis outcomes while minimizing antibiotic-related adverse events.