JAMA Intern Med

Early antibiotic de-escalation in sepsis associated with lower mortality, reduced complications

January 12, 2026

In a target-trial emulation of 36,924 adults hospitalized with community-onset sepsis, de-escalating anti-methicillin-resistant Staphylococcus aureus (MRSA) and anti-Pseudomonas aeruginosa (PSA) coverage on day 4 among those with no evidence of multidrug-resistant organisms (MDROs) was associated with similar 90-day all-cause mortality compared with continued broad-spectrum therapy (anti-MRSA: odds ratio [OR], 1.00; 95% confidence interval [CI], 0.88-1.14; anti-PSA: OR, 0.98; 95% CI, 0.86-1.13). Patients in the de-escalation group also had significantly fewer antibiotic days and shorter hospital stays.

Clinical takeaway: For clinically stable sepsis patients without MDROs, de-escalating broad-spectrum antibiotics on day 4 may reduce exposure and hospitalization without compromising safety.

Source:

Gupta AB, et al. (2025, December 22). JAMA Intern Med. Antibiotic De-Escalation in Adults Hospitalized for Community-Onset Sepsis. https://pubmed.ncbi.nlm.nih.gov/41428290/