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PURPOSE OF REVIEW The traditional approach to sepsis treatment utilizes broad-spectrum antibiotics. Unfortunately, a significant proportion of infected patients have \'culture-negative\' sepsis despite appropriate microbiologic assessment. RECENT FINDINGS There has been increased interest in the past decade on the treatment of culture-negative sepsis. Outcome data comparing culture-negative sepsis with culture-positive sepsis are mixed and it is unclear if culture-negative sepsis is a distinct entity. Recent recommendations promoting antibiotic de-escalation in culture-negative sepsis can be difficult to implement. A variety of strategies have been suggested for limiting antibiotic courses among patients with negative cultures, including limiting antibiotic durations, use of antibiotic stewardship programs, early consideration of narrow antibiotics, rapid diagnostic technology, and eliminating anti-MRSA therapy based on surveillance swabs. SUMMARY Owing to the difficulty inherent in studying the lack of positive data, and to the uncertainty surrounding diagnosis in patients with culture-negative sepsis, prospective data to guide antibiotic choices are lacking. However, antibiotic de-escalation in culture-negative sepsis is both recommended and feasible in patients showing clinical signs of improvement. Increased use of rapid diagnostics, careful consideration of antibiotic necessity, and antibiotic stewardship programs may result in less antibiotic days and better outcomes.
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