Implementation of beta-lactam Therapeutic Drug Monitoring in clinical practice: A prospective, comparative, interventional study in intensive care unit patients - 27/10/26
, Eva Foinet a, b, Gary Duclos c, Wael Alkassab c, Anthea Deschamps a, b, Elisabeth Jouve a, Jeffrey Lipman d, e, Lionel Velly f, Marc Leone cHighlights |
• | This prospective and comparative clinical trial on 172 ICU patients studied the impact of the implementation of beta-lactams therapeutic drug monitoring in clinical practice. |
• | Results did not show a beneficial association both on the PK/PD target attainment and the clinical sides. |
• | These results highlight the persisting challenge of reaching aggressive beta-lactam PK/PD targets, despite the use of high doses administered by continuous infusion. |
• | These results underscores the importance of integrating a protocolised dose adaptation algorithm in TDM practice. |
• | Regarding side effects, our results confirmed that supratherapeutic exposure and acute kidney disease increased the risk of beta-lactam neurotoxicity. |
Abstract |
Background |
This study aimed to evaluate whether implementation of TDM of beta-lactams in clinical practice improved the achievement of PK/PD targets and clinical outcomes in a population of ICU patients receiving high doses by continuous infusion.
Methods |
It was a prospective, comparative, non-randomised, and interventional study conducted in two ICUs (11/2018 to 01/2021), in which TDM of beta-lactams was sequentially implemented. Eligible patients were aged 18 years or older, treated with one of the following five beta-lactams administered in continuous infusion: cefepime, ceftazidime, cefotaxime, piperacillin/tazobactam, and meropenem. The primary endpoint was the PK/PD target attainment at D4 and D7.
Results |
In the non-TDM group (n = 60), 54%, 46%, and 25% of patients reached the targets at D1, D4, and D7 vs. 51%, 57%, and 57% in the TDM group (n = 112), respectively. Target achievement at D4 or D7 was not correlated with TDM implementation ( p = 0.89), unlike reaching the target concentrations at D1 ( p < 0.001) and a documented infection ( p = 0.008). There was no significant difference in electroencephalogram (EEG) neurotoxicity at D4 between the TDM and the non-TDM groups (10% vs. 18%, p = 0.34). A concentration at D1 and/or D4 above the toxicity threshold was reported in patients with acute kidney dysfunction (OR: 8.5 [2.1; 35.4], p = 0.002) and associated with neurotoxicity (OR: 6.0 [1.7; 21.7], p = 0.005).
Conclusions |
In this study, the implementation of TDM did not significantly impact PK/PD target attainment, which underscores the importance of integrating a protocolised dose adaptation algorithm. Neurological adverse events were associated with drug overexposure and kidney function impairment.
Registration |
ClinicalTrials.gov, under I.D. NCT03339869.
Le texte complet de cet article est disponible en PDF.Keywords : Beta-lactams, Therapeutic drug monitoring, Pharmacokinetics, Intensive care, Neurotoxicity
Plan
Vol 46 - N° 2
Article 101929- mars 2027 Retour au numéro
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