Encephalopathy in mechanically ventilated adult patients in the intensive care unit: the role of β-Lactam overdosing.
| Title: | Encephalopathy in mechanically ventilated adult patients in the intensive care unit: the role of β-Lactam overdosing. |
|---|---|
| Authors: | Gendreau S; AP-HP, Hôpitaux Universitaires Henri-Mondor, Service de Médecine Intensive Réanimation, 94010, Créteil, France. segolene.gendreau@aphp.fr.; Université Paris Est Créteil, Faculté de Médecine de Créteil, Institut Mondor de Recherche Biomédicale-Groupe de recherche clinique CARMAS, 94000, Créteil, France. segolene.gendreau@aphp.fr.; Université Paris Est Créteil, INSERM, IMRB, 94010, Créteil, France. segolene.gendreau@aphp.fr.; Benelli B; AP-HP, Hôpitaux Universitaires Henri-Mondor, Service de Médecine Intensive Réanimation, 94010, Créteil, France.; Cintrat G; AP-HP, Hôpitaux Universitaires Henri-Mondor, Service de Médecine Intensive Réanimation, 94010, Créteil, France.; Dufranc E; AP-HP, Hôpitaux Universitaires Henri-Mondor, Service de Médecine Intensive Réanimation, 94010, Créteil, France.; Arrestier R; AP-HP, Hôpitaux Universitaires Henri-Mondor, Service de Médecine Intensive Réanimation, 94010, Créteil, France.; Bay P; AP-HP, Hôpitaux Universitaires Henri-Mondor, Service de Médecine Intensive Réanimation, 94010, Créteil, France.; Chantelot L; AP-HP, Hôpitaux Universitaires Henri-Mondor, Service de Médecine Intensive Réanimation, 94010, Créteil, France.; Labedade P; AP-HP, Hôpitaux Universitaires Henri-Mondor, Service de Médecine Intensive Réanimation, 94010, Créteil, France.; Moncomble E; AP-HP, Hôpitaux Universitaires Henri-Mondor, Service de Médecine Intensive Réanimation, 94010, Créteil, France.; Carteaux G; AP-HP, Hôpitaux Universitaires Henri-Mondor, Service de Médecine Intensive Réanimation, 94010, Créteil, France.; Université Paris Est Créteil, Faculté de Médecine de Créteil, Institut Mondor de Recherche Biomédicale-Groupe de recherche clinique CARMAS, 94000, Créteil, France.; Université Paris Est Créteil, INSERM, IMRB, 94010, Créteil, France.; de Prost N; AP-HP, Hôpitaux Universitaires Henri-Mondor, Service de Médecine Intensive Réanimation, 94010, Créteil, France.; Université Paris Est Créteil, Faculté de Médecine de Créteil, Institut Mondor de Recherche Biomédicale-Groupe de recherche clinique CARMAS, 94000, Créteil, France.; Université Paris Est Créteil, INSERM, IMRB, 94010, Créteil, France.; Hulin A; Université Paris Est Créteil, INSERM, IMRB, 94010, Créteil, France.; AP-HP, Hôpitaux Universitaires Henri Mondor, Laboratoire de Pharmacologie, 94010, Créteil, France.; Pressiat C; Université Paris Est Créteil, INSERM, IMRB, 94010, Créteil, France.; AP-HP, Hôpitaux Universitaires Henri Mondor, Laboratoire de Pharmacologie, 94010, Créteil, France.; Mekontso Dessap A; AP-HP, Hôpitaux Universitaires Henri-Mondor, Service de Médecine Intensive Réanimation, 94010, Créteil, France.; Université Paris Est Créteil, Faculté de Médecine de Créteil, Institut Mondor de Recherche Biomédicale-Groupe de recherche clinique CARMAS, 94000, Créteil, France.; Université Paris Est Créteil, INSERM, IMRB, 94010, Créteil, France.; Razazi K; AP-HP, Hôpitaux Universitaires Henri-Mondor, Service de Médecine Intensive Réanimation, 94010, Créteil, France.; Université Paris Est Créteil, Faculté de Médecine de Créteil, Institut Mondor de Recherche Biomédicale-Groupe de recherche clinique CARMAS, 94000, Créteil, France.; Université Paris Est Créteil, INSERM, IMRB, 94010, Créteil, France. |
| Corporate Authors: | ADEL study group |
| Source: | Scientific reports [Sci Rep] 2026 Feb 24; Vol. 16 (1). Date of Electronic Publication: 2026 Feb 24. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: London : Nature Publishing Group, copyright 2011- |
| MeSH Terms: | Respiration, Artificial*/adverse effects ; beta-Lactams*/adverse effects ; beta-Lactams*/administration & dosage ; Anti-Bacterial Agents*/adverse effects ; Anti-Bacterial Agents*/administration & dosage ; Brain Diseases*/chemically induced ; Brain Diseases*/etiology ; Delirium*/chemically induced ; Delirium*/etiology; Coma/chemically induced ; Humans ; Intensive Care Units ; Female ; Male ; Middle Aged ; Aged ; Adult ; Prospective Studies |
| Abstract: | Delirium is common in ICU and the neurotoxicity induced by antibiotics could be at least in part responsible for it. This study explored the association between β-Lactam overdosing and persistent coma or delirium in patients under mechanical ventilation. All adult patients admitted in ICU receiving continuous sedation were included. β-Lactam's concentrations were collected during sedation, and up to 48 h after end of continuous sedation. Antibiotic dosings were performed 24 h after initiation or after changing the dose or every 48 h. Overdosing was defined as β-Lactam concentrations above the target for the most resistant pathogen empirically considered, therefore 8 times its clinical breakpoint (BP) according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST). The primary outcome was encephalopathy, defined as either delirium or persistent coma during the 48 h following sedation removal. 224 mechanically ventilated patients were prospectively included, and 190 patients assessed for primary outcome. 58% of patients presented an encephalopathy (30/111 persistent coma and 81/111 delirium), and had longer ventilation duration, more extubation failure, longer ICU length of stay, and higher mortality. β-Lactam overdosing rate was similar in patients with or without encephalopathy. Factors associated with encephalopathy were age, sedation duration and SOFA score. A subgroup analysis suggested an association of encephalopathy with overdosing when defined as per published neurotoxic thresholds. β-Lactam's overdosing was not associated with occurrence of encephalopathy. These data highlight the complexity of delayed awakening and may suggest to broadening the identification of neurotoxic thresholds of individual antibiotics in further studies.; (© 2026. The Author(s).) |
| Competing Interests: | Declarations. Ethics approval and consent to participate: This observational prospective study was approved by the Institutional Review Board of the French intensive care medicine society (CE SRLF 17-48) and written and oral information about the study was given to the patients. The data were anonymously collected from medical files in a secure database declared to the National Commission for Information Technology and Civil Liberties. Competing interests: The authors declare no competing interests. |
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| Contributed Indexing: | Investigator: S Gendreau; B Benelli; G Cintrat; P Labedade; E Moncomble; P Bay; R Arrestier; S Mokhtari; A Renou; D Clausse; P Cirera; A Fogang; V Anton Raj; AF Haudebourg; G Rousseau; A Daulasim; A Baron; L Beaudeau; E Berti; F Biancale; A Bourouchaki; M Ren; M Roue; R Schramm; Keywords: Antibiotics; Coma; Delirium; Encephalopathy; Neurotoxicity; Therapeutic drug monitoring |
| Substance Nomenclature: | 0 (beta-Lactams); 0 (Anti-Bacterial Agents) |
| Entry Date(s): | Date Created: 20260224 Date Completed: 20260328 Latest Revision: 20260330 |
| Update Code: | 20260418 |
| PubMed Central ID: | PMC13031709 |
| DOI: | 10.1038/s41598-026-38709-y |
| PMID: | 41735415 |
| Database: | MEDLINE |
Journal Article