Prospective evaluation of imipenem trough concentrations and clinical outcomes in critically ill patients

Article Article scientifique Article Prospective evaluation of imipenem trough concentrations and clinical outcomes in critically ill patients eng 2026-08-04 author Liden Mia Madeleine 0009-0009-5207-2931 Paediatric Department, Geneva University Hospitals and Faculty of Medicine, Rue Willy-Donzé 6, Geneva 1205, Switzerland. 874439 author Boroli Filippo Intensive Care Unit, Geneva University Hospitals, Rue Gabrielle Perret-Gentil 4, Geneva 1205, Switzerland. 791594 author Von Dach-Saouter Elodie Centre for Clinical Research, Clinical Trials Unit, University Hospital and University of Geneva, Rue Gabrielle Perret-Gentil 4, Geneva 1205, Switzerland. 591850 author Lescuyer Pierre 0000-0001-6986-8738 Toxicology and Therapeutic Drug Monitoring Laboratory, Geneva University Hospitals, Rue Gabrielle Perret-Gentil 4, Geneva 1205, Switzerland. 562350 author Tonoli David Toxicology and Therapeutic Drug Monitoring Laboratory, Geneva University Hospitals, Rue Gabrielle Perret-Gentil 4, Geneva 1205, Switzerland. 664012 author Csaki Huttner Angela Infectious Disease Division, Geneva University Hospitals and Faculty of Medicine, Rue Gabrielle Perret-Gentil 4, Geneva 1205, Switzerland. 788122 Département de médecine (DEMED) OPTIMAL TDM Study Group collaborator Karmime Abderrahim 29133 collaborator Pfister Rosanne 699590 collaborator Harbarth Stéphan Juergen 0000-0002-3551-1025 93885 Département de médecine (DEMED) collaborator Huttner Benedikt 0000-0002-1749-9464 666500 collaborator Ing Roselyne collaborator Neofytos Dionysios 911674 Département de médecine (DEMED) collaborator Prendki Virginie 0000-0003-1315-2938 811987 dept de réadaptation et gériatrie (MIGRG) collaborator Roux Xavier 848507 dept de réadaptation et gériatrie (MIGRG) dkag242 10.1093/jac/dkag242 42610959 0305-7453 PMC13482977 https://academic.oup.com/jac/article/81/9/dkag242/8763731 Background: Imipenem is a broad-spectrum antibiotic commonly used in critically ill patients, whose pharmacokinetic profile can be highly variable. While imipenem therapeutic drug monitoring (TDM) is being adopted increasingly, efficacy and toxicity plasma thresholds remain incompletely defined. Few studies have prospectively and systematically assessed imipenem concentrations in severely ill patients before clinical failure or toxicity events occur. Methods: This prospective observational cohort study conducted at the University Hospitals of Geneva consecutively included all adult patients hospitalized for suspected or confirmed severe bacterial infections in the haematology, intermediate care and intensive care units whose clinicians prescribed imipenem. On inclusion, patients underwent imipenem plasma-concentration monitoring, with trough levels measured at steady state. We assessed the frequency of adverse events and clinical success over a 30-day period. Results: Of 142 patients undergoing imipenem monitoring, 106 had trough levels drawn at steady state. The median trough concentration was 2.4 mg/L (IQR 1.2-4.0). Among all patients, adverse events occurred in 4.9% (7/142), while clinical success was achieved in 88/106 with trough levels (83%). No significant differences in trough levels were observed between patients with and without clinical success or with and without adverse events. Renal clearance had a significant impact on trough levels. Conclusion: Prospective, universally applied imipenem monitoring reveals lower trough levels than previously described. Nonetheless, this cohort of critically ill and/or immunosuppressed patients still experienced high rates of clinical success, with few adverse events. While low trough concentrations did not predict failure, rare outlying higher concentrations (10-20 mg/L) also did not predict toxicity. Humans Imipenem / pharmacokinetics Imipenem / adverse effects Imipenem / therapeutic use Imipenem / blood Imipenem / administration & dosage Critical Illness Female Prospective Studies Anti-Bacterial Agents / pharmacokinetics Anti-Bacterial Agents / adverse effects Anti-Bacterial Agents / therapeutic use Anti-Bacterial Agents / administration & dosage Anti-Bacterial Agents / blood Male Middle Aged Aged Treatment Outcome Bacterial Infections / drug therapy Drug Monitoring Adult Plasma / chemistry Switzerland Hospitals, University Aged, 80 and over Dewey 616 Dewey 617 Dewey 618 Dewey 618.97 Geneva University Hospital Research and Developpement PRD 8-2017-2 56 Département de médecine 221 63 Département d'anesthésiologie, pharmacologie, soins intensifs et urgences 229 217 Centre de recherche clinique 201 58 Département de pédiatrie, gynécologie et obstétrique 223 65 Département de réadaptation et gériatrie 22B false 526 Résistance aux antibiotiques 866 211 Auto-immunité, inflammation et athérosclérose 270 1466 Infections urinaires, résistance antimicrobienne et optimisation de l'antibiothérapie 1076 1440 Infections de la personne âgée 1062 Journal of antimicrobial chemotherapy 81 9 c89151d4-1f3f-4e85-8afd-b9ffd4e84535 Article (Published version) Public Stephan_Harbarth_-_Prospective_eval.pdf 477848 application/pdf CC BY-4.0 b1aafe13fdb7ee27e4508850a6289b331ea9e12969b03bd42bba968026a7d83a 91736035-3b89-4a14-8a0d-e203bcb05edf Supplemental data Public dkag242_supplementary_data.docx 7435792 application/vnd.openxmlformats-officedocument.wordprocessingml.document 3288fc9cbba663188ffd498375b19028e210aeea649aafed9546c4d02accd468 openAccess Faculté de médecine / Section de médecine clinique / Département de médecine Faculté de médecine / Section de médecine clinique / Département d'anesthésiologie, pharmacologie, soins intensifs et urgences Faculté de médecine / Centre de recherche clinique Faculté de médecine / Section de médecine clinique / Département de pédiatrie, gynécologie et obstétrique Faculté de médecine / Section de médecine clinique / Département de réadaptation et gériatrie

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Prospective evaluation of imipenem trough concentrations and clinical outcomes in critically ill patients	Journal of antimicrobial chemotherapy			2026	1	0

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Pfister, Rosanne