Randomized Controlled Trial

. 2025 Aug;51(8):1417-1430.

doi: 10.1007/s00134-025-08014-9. Epub 2025 Jul 15.

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

Guillaume Voiriot¹, Laurent Argaud², Yves Cohen^#³, Sophie Tuffet^#⁴, Louis Chauvelot⁵, Bertrand Souweine⁶, Kada Klouche⁷, Jean Reignier⁸, Carole Schwebel⁹, Anahita Rouzé¹⁰, Armand Mekontso Dessap¹¹, Julien Bohé¹², Bruno Megarbane¹³, Julien Carvelli¹⁴, Jean-Christophe Navellou¹⁵, Sébastien Gibot¹⁶, Éric Maury¹⁷, Jean Dellamonica¹⁸, Pierre-François Dequin¹⁹, Julien Dessajan²⁰, Laurence Armand-Lefèvre²¹, Francois Vandenesch^{22

23}, Charlotte Verdet²⁴, Isabelle Durand Zaleski²⁵, Laurence Bérard⁴, Alexandra Rousseau⁴, Simon Tabassome⁴, Muriel Fartoukh^#²⁶, Jean-François Timsit^#²⁷; MULTI-CAP collaborative trial group

Collaborators, Affiliations

Collaborators

Affiliations

¹ Sorbonne Université, Assistance Publique - Hôpitaux de Paris, Service de Médecine Intensive Réanimation, Hôpital Tenon, GRC SoLID, INSERM Centre de Recherche Saint-Antoine UMRS_938 Team 5PMed, Paris, France. guillaume.voiriot@aphp.fr.
² Service de Médecine Intensive-Réanimation, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.
³ Assistance Publique-Hôpitaux de Paris, Service de Réanimation Médico-Chirurgicale, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Bobigny, France.
⁴ Assistance Publique-Hôpitaux de Paris, Unité de Recherche Clinique de l'Est Parisien, Sorbonne Université, Hôpital Saint-Antoine, Paris, France.
⁵ Service de Médecine Intensive Réanimation, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France.
⁶ Service de Médecine Intensive Et Réanimation, Centre Hospitalier Universitaire Gabriel Montpied, Clermont-Ferrand, France.
⁷ Intensive Care Medicine Department, Lapeyronie University Hospital, Montpellier, France.
⁸ Service de Médecine Intensive Réanimation, Centre Hospitalier Universitaire de Nantes, Nantes, France.
⁹ Service de Médecine Intensive Réanimation, Centre Hospitalier Universitaire Grenoble-Alpes, INSERM U1039, La Tronche, France.
¹⁰ Centre Hospitalier Universitaire de Lille, U1285-UMR 8576-UGSF-Unité de Glycobiologie Structurale et Fonctionnelle, Service de Médecine Intensive Réanimation, Université de Lille, CNRS, INSERM, Lille, France.
¹¹ Assistance Publique-Hôpitaux de Paris, Service de Médecine Intensive Réanimation, Université Paris Est CréteilHôpitaux Universitaires Henri-Mondor, Hôpital Henri MondorCARMAS, Créteil, France.
¹² Service d'Anesthésie Réanimation Médecine Intensive, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyo, n, Pierre Bénite, France.
¹³ Department of Medical and Toxicological Critical Care, Lariboisière Hospital, Université Paris Cité, INSERM UMRS-1144, Paris, France.
¹⁴ Service de Médecine Intensive Réanimation, Hôpital Timone, Assistance Publique- Hôpitaux de Marseille, C2VN-Aix Marseille Université, Marseille, France.
¹⁵ Service de Médecine Intensive Réanimation, Centre Hospitalier Universitaire de Besançon, Besançon, France.
¹⁶ Service de Médecine Intensive Réanimation, Centre Hospitalier Universitaire de Nancy, Hôpital Central, Nancy, France.
¹⁷ Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Antoine, Médecine Intensive et Réanimation, Sorbonne Université, Paris, France.
¹⁸ Service de Médecine Intensive et Réanimation, Centre Hospitalier Universitaire de Nice, UR2CA -Unité de Recherche Clinique Côte d'Azur, Université Côte d'Azur, Nice, France.
¹⁹ Intensive Care Unit, Research Center for Respiratory Diseases, Tours University Hospital, INSERM U1100, University of Tours, Tours, France.
²⁰ Service de Médecine Intensive Réanimtion Infectieuse, Assistance Publique - Hôpitaux de Paris, Hôpital Bichat, Paris, France.
²¹ Service de Bactériologie, UMR 1137, Université Paris Cité, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, IAME INSERM, Paris, France.
²² Institut Des Agents Infectieux, Hospices Civils de Lyon, Lyon, France.
²³ Inserm U1111, CIRI, Université de Lyon, Université Claude Bernard Lyon 1, CNRS UMR5308, ENS de Lyon, Lyon, France.
²⁴ Service de Bactériologie-Hygiène, Hôpital Saint-Antoine, GHU AP-HP, Sorbonne Université, AP-HP, Paris, France.
²⁵ Assistance Publique-Hôpitaux de Paris, URCeco Santé Publique, CRESS METHODS-UMR1153-INSERM, Université Paris est Créteil, Paris, France.
²⁶ Assistance Publique-Hôpitaux de Paris, Service de Médecine Intensive Réanimation, Sorbonne Université, Hopital Tenon, GRC CARMAS, Paris, France.
²⁷ Service de Médecine Intensive Réanimation Infectieuse, UMR 1137-IAME Team 5-DeSCID: Decision Sciences in Infectious Diseases Control and Care, Université Paris Cité, Assistance Publique - Hôpitaux de Paris, Hôpital Bichat, INSERM, Paris, France.

^# Contributed equally.

PMID: 40663137
DOI: 10.1007/s00134-025-08014-9

Randomized Controlled Trial

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

Guillaume Voiriot et al. Intensive Care Med. 2025 Aug.

. 2025 Aug;51(8):1417-1430.

doi: 10.1007/s00134-025-08014-9. Epub 2025 Jul 15.

Authors

Collaborators

Affiliations

¹ Sorbonne Université, Assistance Publique - Hôpitaux de Paris, Service de Médecine Intensive Réanimation, Hôpital Tenon, GRC SoLID, INSERM Centre de Recherche Saint-Antoine UMRS_938 Team 5PMed, Paris, France. guillaume.voiriot@aphp.fr.
² Service de Médecine Intensive-Réanimation, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.
³ Assistance Publique-Hôpitaux de Paris, Service de Réanimation Médico-Chirurgicale, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Bobigny, France.
⁴ Assistance Publique-Hôpitaux de Paris, Unité de Recherche Clinique de l'Est Parisien, Sorbonne Université, Hôpital Saint-Antoine, Paris, France.
⁵ Service de Médecine Intensive Réanimation, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France.
⁶ Service de Médecine Intensive Et Réanimation, Centre Hospitalier Universitaire Gabriel Montpied, Clermont-Ferrand, France.
⁷ Intensive Care Medicine Department, Lapeyronie University Hospital, Montpellier, France.
⁸ Service de Médecine Intensive Réanimation, Centre Hospitalier Universitaire de Nantes, Nantes, France.
⁹ Service de Médecine Intensive Réanimation, Centre Hospitalier Universitaire Grenoble-Alpes, INSERM U1039, La Tronche, France.
¹⁰ Centre Hospitalier Universitaire de Lille, U1285-UMR 8576-UGSF-Unité de Glycobiologie Structurale et Fonctionnelle, Service de Médecine Intensive Réanimation, Université de Lille, CNRS, INSERM, Lille, France.
¹¹ Assistance Publique-Hôpitaux de Paris, Service de Médecine Intensive Réanimation, Université Paris Est CréteilHôpitaux Universitaires Henri-Mondor, Hôpital Henri MondorCARMAS, Créteil, France.
¹² Service d'Anesthésie Réanimation Médecine Intensive, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyo, n, Pierre Bénite, France.
¹³ Department of Medical and Toxicological Critical Care, Lariboisière Hospital, Université Paris Cité, INSERM UMRS-1144, Paris, France.
¹⁴ Service de Médecine Intensive Réanimation, Hôpital Timone, Assistance Publique- Hôpitaux de Marseille, C2VN-Aix Marseille Université, Marseille, France.
¹⁵ Service de Médecine Intensive Réanimation, Centre Hospitalier Universitaire de Besançon, Besançon, France.
¹⁶ Service de Médecine Intensive Réanimation, Centre Hospitalier Universitaire de Nancy, Hôpital Central, Nancy, France.
¹⁷ Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Antoine, Médecine Intensive et Réanimation, Sorbonne Université, Paris, France.
¹⁸ Service de Médecine Intensive et Réanimation, Centre Hospitalier Universitaire de Nice, UR2CA -Unité de Recherche Clinique Côte d'Azur, Université Côte d'Azur, Nice, France.
¹⁹ Intensive Care Unit, Research Center for Respiratory Diseases, Tours University Hospital, INSERM U1100, University of Tours, Tours, France.
²⁰ Service de Médecine Intensive Réanimtion Infectieuse, Assistance Publique - Hôpitaux de Paris, Hôpital Bichat, Paris, France.
²¹ Service de Bactériologie, UMR 1137, Université Paris Cité, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, IAME INSERM, Paris, France.
²² Institut Des Agents Infectieux, Hospices Civils de Lyon, Lyon, France.
²³ Inserm U1111, CIRI, Université de Lyon, Université Claude Bernard Lyon 1, CNRS UMR5308, ENS de Lyon, Lyon, France.
²⁴ Service de Bactériologie-Hygiène, Hôpital Saint-Antoine, GHU AP-HP, Sorbonne Université, AP-HP, Paris, France.
²⁵ Assistance Publique-Hôpitaux de Paris, URCeco Santé Publique, CRESS METHODS-UMR1153-INSERM, Université Paris est Créteil, Paris, France.
²⁶ Assistance Publique-Hôpitaux de Paris, Service de Médecine Intensive Réanimation, Sorbonne Université, Hopital Tenon, GRC CARMAS, Paris, France.
²⁷ Service de Médecine Intensive Réanimation Infectieuse, UMR 1137-IAME Team 5-DeSCID: Decision Sciences in Infectious Diseases Control and Care, Université Paris Cité, Assistance Publique - Hôpitaux de Paris, Hôpital Bichat, INSERM, Paris, France.

^# Contributed equally.

PMID: 40663137
DOI: 10.1007/s00134-025-08014-9

Abstract

Purpose: Multiplex polymerase chain reaction (mPCR) testing has the potential to rapidly and accurately identify causative microorganisms in patients with community-acquired pneumonia (CAP). Its use in a management strategy, along with biomarkers, may reduce antibiotic exposure and improve clinical outcomes.

Methods: The MULTI-CAP trial was a multicenter (n = 20), parallel-group, superiority, open-label, randomized trial. Subjects were non-immunocompromised adult patients (≥ 18 years) admitted to the intensive care unit (ICU) for CAP and randomly assigned in a 1:1 ratio. In the intervention group, the microbiological diagnosis combined a broad-spectrum respiratory mPCR and conventional microbiological investigations. An algorithm for early discontinuation or de-escalation of antibiotics was applied, based on mPCR results and serum procalcitonin. In the control group, only conventional microbiological investigations were performed. In both groups, antibiotic discontinuation was considered on Day 3 and day after day until Day 7, based on procalcitonin values and kinetics. The primary endpoint was defined as the number of days alive without any antibiotic from the time of enrollment to Day 28.

Results: From October 4, 2018, to March 3, 2022, 406 patients were randomized, and 385 were evaluable in the intention-to-treat analysis. The median number of days alive without antibiotics on Day 28 was 19.0 (0.0; 24.0) days in the intervention group and 19.0 (7.0; 22.0) days in the control group (difference, 0.0 (95% CI, - 4.0 to 4.0). However, the antibiotic cumulative duration on day 28 was 3 days shorter (95% CI, - 5.1 to - 0.9) in the intervention group. Serious adverse events did not differ between groups.

Conclusion: In ICU patients with CAP, a management strategy combining a mPCR and serum procalcitonin failed to reduce antibiotic exposure or improve outcomes on Day 28, compared to usual care.

Trial registration number: NCT03452826 (March 2018), EudraCT 2017-A01615-48.

Keywords: Community-acquired pneumonia; Critically ill; Intensive care medicine; Molecular diagnosis.

PubMed Disclaimer

Conflict of interest statement

Declarations. Conflicts of interest: Laurence Armand-Lefèvre received consulting fees from Shionogi and Viatris, and honoraria for lectures from Advanz, Shionogi and Pfizer. In addition, she performed unpaid lectures for BioMérieux and Qiagen. Julien Dessajan received honoraria for lectures from BioMérieux. Isabelle Durand-Zaleski received consulting fees from Bristol Myers Squibb, MSD, Sanofi, Pfizer and Roche. Muriel Fartoukh reported research grants from BioMérieux and personal fees from BioMérieux, Pfizer, SOS Oxygene and Fisher and Paykel. Tabassome Simon reported support for research from BioMérieux, research grants from Astra Zeneca, Bayer, Boehringer, Daiichi Sankyo, Ili-Lilly, GSK, Novartis and Sanofi, and honoraria for lectures from Servier and Novartis. In addition, she reported participation in Data Safety Monitoring Board for Ablative Solutions, Air Liquide, Astra Zeneca, Sanofi, Novartis and 4Living Biotech. Jean-Francois Timsit Simon reported support for research from BioMérieux, and consulting fees from Advanz, Menarini, Pfizer and Merck. In addition, he reported honoraria for lectures from BioMérieux, MundiPharma and Merck. Guillaume Voiriot reported research grants from BioMérieux and SOS Oxygene, and support for attending meetings from Oxyvie. Francois Vandenesch reported been founder and shareholder of Weezion.

References

1. Rhee C, Kadri SS, Dekker JP, Danner RL, Chen HC, Fram D et al (2020) Prevalence of antibiotic-resistant pathogens in culture-proven sepsis and outcomes associated with inadequate and broad-spectrum empiric antibiotic use. JAMA Netw Open 3(4):e202899
1. Webb BJ, Sorensen J, Jephson A, Mecham I, Dean NC (2019) Broad-spectrum antibiotic use and poor outcomes in community-onset pneumonia: a cohort study. Eur Respir J Juill 54(1):1900057
1. Dinh A, Ropers J, Duran C, Davido B, Deconinck L, Matt M et al (2021) Discontinuing β-lactam treatment after 3 days for patients with community-acquired pneumonia in non-critical care wards (PTC): a double-blind, randomised, placebo-controlled, non-inferiority trial. Lancet Lond Engl 397(10280):1195–203
1. Schuetz P, Wirz Y, Sager R, Christ-Crain M, Stolz D, Tamm M et al (2018) Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis. Lancet Infect Dis 18(1):95–107
1. de Jong E, van Oers JA, Beishuizen A, Vos P, Vermeijden WJ, Haas LE et al (2016) Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial. Lancet Infect Dis 16(7):819–827

Publication types

Actions
Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions

Associated data

Actions
- Search in PubMed
- Search in ClinicalTrials.gov

LinkOut - more resources

Full Text Sources
- Springer
Medical
- ClinicalTrials.gov
- MedlinePlus Health Information
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Collaborators

Affiliations

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

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Substances

Associated data

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous