Day 4 Antibiotic De-Escalation in Community-Onset Sepsis Is Safe, Reduces Antibiotic Exposure

Background: Empiric broad-spectrum antibiotics (BSAs) are central to early sepsis care, but prolonged exposure increases risks, including adverse drug events, Clostridioides difficile , and antimicrobial resistance. Guidelines recommend de-escalation when resistant organisms are not identified, although real-world safety data remain mixed. Objective: To evaluate whether de-escalation of BSAs by hospital day 4 is associated with worse outcomes compared to continuation in patients with community-onset sepsis without multidrug-resistant organism (MDRO) infection. Design: Multicenter, target trial emulation, observational study. Participants/Methods: Among 36,924 adults hospitalized with community-onset sepsis, 16,860 patients receiving empiric anti–methicillin-resistant Staphylococcus aureus (MRSA) or antipseudomonal therapy without early MDRO positivity were included from 67 hospitals in the Michigan Hospital Medicine Safety Consortium. The exposure was de-escalation versus conti more...