Understanding the ADAPT-Sepsis Trial: PCT vs. CRP-Guided Antibiotic Duration
Sepsis remains a critical challenge in intensive care units (ICUs), often requiring prolonged antibiotic use. The ADAPT-Sepsis trial, published in JAMA (2024), aimed to determine whether procalcitonin (PCT)-guided or C-reactive protein (CRP)-guided antibiotic discontinuation strategies could safely reduce antibiotic duration compared to standard care.
Study Overview
This multicenter randomized controlled trial included 2,761 critically ill patients admitted to the ICU with suspected sepsis. The key objective was to assess whether biomarker-guided antibiotic discontinuation could shorten antibiotic duration without increasing 28-day all-cause mortality.
Study Groups
Patients were randomized into three groups:
- PCT-Guided Protocol (N = 918)
- CRP-Guided Protocol (N = 924)
- Standard Care (N = 918)
Key Findings
Primary Outcome: Total Antibiotic Duration
- PCT-guided group: 9.8 days (0.88 days reduction compared to standard care, p = 0.01)
- CRP-guided group: 10.6 days (No significant reduction compared to standard care, p = 0.79)
- Standard care: 10.7 days
➡ Takeaway: PCT guidance significantly reduced antibiotic duration, while CRP guidance did not.
Secondary Outcome: 28-Day All-Cause Mortality
- PCT group: 20.9% mortality (1.57% increase vs. standard care, p = 0.02)
- CRP group: 21.1% mortality (1.69% increase vs. standard care, p = 0.03)
- Standard care: 19.4% mortality
➡ Takeaway: While PCT reduced antibiotic exposure, there was a slight increase in mortality, but confidence intervals were wide, making conclusions uncertain. CRP guidance did not provide a clear benefit.
Conclusion
The ADAPT-Sepsis trial provides valuable insights into antibiotic stewardship in sepsis management:
- PCT-guided antibiotic discontinuation effectively reduces antibiotic duration.
- CRP-guided discontinuation does not reduce antibiotic use compared to standard care.
- All-cause mortality for CRP was inconclusive, and the small increase in mortality with PCT requires further investigation.
Clinical Implications
For ICU clinicians, PCT-guided antibiotic decisions may be a useful tool to limit unnecessary antibiotic exposure, reducing the risk of resistance and complications. However, caution is required due to the potential mortality signal.
Reference
Dark et al. JAMA Dec 9, 2024. DOI: 10.1001/jama.2024.26458
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