TL;DR: 🟢 Positive — PCT-guided (not CRP-guided) daily antibiotic-discontinuation protocol safely reduced antibiotic duration (~0.9 days) without increasing 28-day mortality.
1. Publication
- Title: Biomarker-Guided Antibiotic Duration for Hospitalized Patients With Suspected Sepsis: The ADAPT-Sepsis Randomized Clinical Trial
- Acronym: ADAPT-Sepsis
- Year & Journal: JAMA, published December 9, 2024 (print: 2025;333(8):682-693)
- Citation: ADAPT-Sepsis Collaborators, Dark P, Hossain A, McAuley DF, et al. JAMA. 2025;333(8):682-693. doi:10.1001/jama.2024.26458
2. Context & Rationale
Background: Prolonged antibiotic courses increase toxicity, C. difficile risk, and resistance selection pressure. Procalcitonin (PCT) and CRP are commonly measured in ICU sepsis, but their use as explicit "stopping rules" is inconsistent and non-protocolized; 2021 Surviving Sepsis guidelines suggested using PCT alongside clinical evaluation without strong evidence.
Research Question/Hypothesis: In hospitalized critically ill adults with suspected sepsis, do PCT-guided or CRP-guided daily protocols safely reduce total antibiotic duration compared with standard care, without increasing 28-day mortality?
3. Design & Methods
- Study Type: Investigator-initiated, multicenter, three-arm, open-label RCT
- Setting & Centers: 41 NHS ICUs, UK; enrolled 2018–June 2024 (paused during 2020 lockdown)
- Population: Critically ill adults with suspected sepsis requiring IV antibiotics
- Intervention: Daily PCT-guided or daily CRP-guided antibiotic discontinuation advice, initiated within 24h of starting IV antibiotics, continuing up to 28 days
- Comparator: Standard care guidance (no biomarker input)
- Randomization: 3-arm, 2760 patients
- Blinding: Open-label
- Statistical Power & Follow-Up: Primary effectiveness: total antibiotic days to day 28. Primary safety: 28-day all-cause mortality.
4. Key Results
2760 patients randomized.
Outcome | PCT-Guided | CRP-Guided | Standard Care | Notes |
Total antibiotic days to day 28 (primary) | Reduced (~0.9 day mean difference) | Not significantly reduced | Reference | PCT protocol significantly shortened antibiotic exposure |
28-day mortality (safety) | Not increased | Inconclusive | Reference | PCT-guided arm showed no mortality signal; CRP-guided results inconclusive |
5. Internal Validity Assessment
Large (2760-patient), multicenter, 3-arm RCT with a hard safety endpoint (mortality) alongside the primary effectiveness endpoint. Overall: Strong — addresses both effectiveness and safety explicitly; open-label design is a limitation but antibiotic-day counting and mortality are relatively objective.
6. External Validity Assessment
UK NHS ICU population, broadly representative of suspected sepsis requiring IV antibiotics in similar high-resource critical care systems.
7. Strengths & Limitations
Strengths: Large, 3-arm design directly comparing two biomarkers against standard care; both effectiveness and safety explicitly powered; long recruitment across many centers strengthens generalizability.
Limitations: Open-label; CRP-guided arm results less clear-cut than PCT; enrollment interrupted by COVID-19 lockdown, introducing potential temporal heterogeneity.
8. Interpretation & Practice Impact
Supports PCT-guided (but not clearly CRP-guided) daily antibiotic-discontinuation protocols to safely shorten antibiotic exposure in suspected sepsis — a modest (~0.9-day) reduction that could meaningfully curb population-level antibiotic overuse and resistance pressure if adopted broadly.
9. Controversies & Subsequent Evidence
Independent commentary (The Bottom Line) notes the BALANCE trial (this handbook) similarly demonstrated non-inferiority for shorter antibiotic durations in bloodstream infections — together these trials reinforce a broader 2024 shift toward shorter, biomarker- or protocol-guided antibiotic courses across sepsis and bacteremia.
10. Summary & Executive Takeaway
Summary: ADAPT-Sepsis randomized 2760 UK ICU patients with suspected sepsis to PCT-guided, CRP-guided, or standard-care antibiotic discontinuation protocols. PCT guidance significantly reduced antibiotic duration (~0.9 days) without increasing 28-day mortality; CRP guidance did not clearly reduce duration.
Overall Takeaway: Daily PCT-guided (not CRP-guided) antibiotic stopping protocols safely shorten antibiotic exposure in suspected sepsis — a modest but potentially important population-level antimicrobial stewardship gain.
11. Bibliography
- The BALANCE Investigators. Antibiotic Treatment for 7 versus 14 Days in Bloodstream Infections. N Engl J Med 2024 (this handbook).
- Surviving Sepsis Campaign International Guidelines 2021. Intensive Care Med. 2021;47(11):1181-1247.