1. Publication
- Title: Combined use of a multiplex PCR and serum procalcitonin to reduce antibiotic exposure in critically ill patients with community-acquired pneumonia: the MULTI-CAP randomized controlled trial
- Acronym: MULTI-CAP
- Year & Journal: Intensive Care Medicine, published July 15, 2025 (2025;51(8):1417-1430)
- Citation: Voiriot G, Argaud L, Cohen Y, et al; MULTI-CAP collaborative trial group. Intensive Care Med. 2025;51(8):1417-1430. doi:10.1007/s00134-025-08014-9
2. Context & Rationale
Background: Multiplex PCR (mPCR) testing can rapidly identify causative organisms in CAP; combined with procalcitonin, it may enable earlier antibiotic de-escalation/discontinuation, reducing selection pressure for antimicrobial resistance — a public health priority.
Research Question/Hypothesis: In non-immunocompromised adults admitted to ICU with CAP, does a management strategy combining broad-spectrum respiratory mPCR plus serum procalcitonin (guiding early antibiotic de-escalation/discontinuation) reduce antibiotic exposure compared with conventional microbiological investigation alone?
3. Design & Methods
- Study Type: Multicenter (20 centers), parallel-group, superiority, open-label RCT
- Setting & Centers: French ICUs; Oct 2018–Aug 2022, 411 patients enrolled
- Population: Non-immunocompromised adults ≥18y admitted to ICU for CAP
- Intervention: Broad-spectrum respiratory mPCR plus conventional microbiology, with an algorithm for early antibiotic de-escalation/discontinuation based on mPCR + serum PCT
- Comparator: Conventional microbiological investigation only
- Randomization: 1:1
- Statistical Power & Follow-Up: Primary: antibiotic-free days at day 28. Secondary: mortality at day 28 and 90.
4. Key Results
411 patients enrolled.
Outcome | mPCR + PCT Strategy | Conventional Care | Notes |
Antibiotic-free days at day 28 (primary) | Not significantly increased | — | Primary endpoint not met |
Cumulative antibiotic duration | Reduced by ≈3 days | — | Reduction seen despite the primary (antibiotic-free-days) endpoint not being statistically met |
Mortality (28d, 90d) | No significant difference | — | No safety signal either direction |
Note on data completeness: Precise numeric antibiotic-free-days values with CI/p-value were not available in the accessible source text; the qualitative pattern (primary endpoint missed, but meaningful cumulative-duration reduction) is drawn from related independent commentary discussing this trial alongside PRONTO and ADAPT-Sepsis in the broader biomarker-guided antibiotic stewardship literature.
5. Internal Validity Assessment
Multicenter, open-label RCT with a clear, prespecified antibiotic-exposure primary outcome. Overall: Moderate — primary endpoint (antibiotic-free days) not statistically met despite a real reduction in cumulative antibiotic duration, a pattern suggesting the specific outcome metric (rather than the intervention itself) may have limited detection of a genuine, smaller effect.
6. External Validity Assessment
French, 20-center ICU CAP population (non-immunocompromised) — broadly representative of general ICU CAP populations in similar health systems with mPCR/PCT testing capability.
7. Strengths & Limitations
Strengths: Multicenter, well-designed antibiotic-stewardship RCT; combines two complementary rapid-diagnostic modalities (mPCR + PCT); real reduction in cumulative antibiotic duration despite primary endpoint miss.
Limitations: Open-label; primary endpoint not statistically achieved; requires mPCR/PCT testing infrastructure.
8. Interpretation & Practice Impact
Does not provide definitive evidence that combined mPCR+PCT-guided antibiotic management improves the specific antibiotic-free-days metric, though it did reduce cumulative antibiotic exposure — joins a broader, genuinely mixed pattern of rapid-diagnostic/stewardship trials (contrast with the positive PRONTO trial, this handbook's 2026 section, which found a mortality benefit despite no stewardship effect; and ADAPT-Sepsis, which safely shortened antibiotic duration).
9. Controversies & Subsequent Evidence
Discussed alongside PRONTO (this handbook, 2026 Sepsis category) and ADAPT-Sepsis in reviewing the 2026 Surviving Sepsis Campaign guideline evidence base — together these trials illustrate that biomarker/rapid-diagnostic-guided antibiotic strategies produce genuinely heterogeneous effects across different specific outcome metrics (stewardship vs mortality vs cumulative duration), an important nuance for interpreting any single trial in isolation.
10. Summary & Executive Takeaway
Summary: MULTI-CAP randomized 411 non-immunocompromised ICU CAP patients across 20 French centers to combined mPCR+PCT-guided antibiotic management or conventional care. The primary outcome (antibiotic-free days at day 28) was not significantly improved, though cumulative antibiotic duration was reduced by approximately 3 days, with no mortality difference.
Overall Takeaway: Combined rapid diagnostics (mPCR) and procalcitonin can meaningfully reduce cumulative antibiotic exposure in ICU CAP patients even without achieving the specific antibiotic-free-days primary endpoint — part of a genuinely mixed, evolving evidence base on biomarker-guided antibiotic stewardship in respiratory infection.
11. Bibliography
- Voiriot G, Fartoukh M, Durand-Zaleski I, et al. MULTI-CAP protocol. BMJ Open. 2021;11(8):e048187.
- Dark P, Hossain A, McAuley DF, et al; ADAPT-Sepsis Collaborators. JAMA. 2025;333(8):682-693.