Reassessing Procalcitonin-Guided Antibiotic Therapy in Critically Ill Patients With Sepsis: Lessons From the ADAPT-Sepsis Trial

Abstract Randomized trials of procalcitonin-guided algorithms to discontinue antibiotics in critically ill patients with sepsis report reduced antibiotic duration and possible mortality benefit. However, open-label trial designs, inconsistent algorithm adherence, and unclear stewardship practices have limited confidence in procalcitonin's benefit. The ADAPT-Sepsis trial addressed several of these gaps through a concealed intervention, robust stewardship, and head-to-head comparison with C-reactive protein (CRP). Procalcitonin-guided care reduced antibiotic use without significantly impacting mortality, although CRP-guided care showed no benefit. However, algorithm adherence was suboptimal, and the absolute reduction in antibiotic duration with procalcitonin was only 1 day. As shorter fixed-duration therapy becomes standard, procalcitonin's utility in the intensive care unit may decline. Embedding procalcitonin and other biomarkers into multifaceted stewardship strategies, and addressing barriers to clinician trust and implementation, is essential. Future research should also evaluate whether biomarker use earlier in the sepsis care pathway, particularly in Emergency Departments, can improve diagnostic accuracy and enhance patient outcomes.