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ß-Lactam Pharmacokinetic/Pharmacodynamic Target Attainment in Intensive Care Unit Patients: A Prospective, Observational, Cohort Study.
Guilhaumou, Romain; Chevrier, Constance; Setti, Jean Loup; Jouve, Elisabeth; Marsot, Amélie; Julian, Nathan; Blin, Olivier; Simeone, Pierre; Lagier, David; Mokart, Djamel; Bruder, Nicolas; Garnier, Marc; Velly, Lionel.
Afiliación
  • Guilhaumou R; Department of Clinical Pharmacology and Pharmacosurveillance, La Timone University Hospital; 13005 Marseille, France.
  • Chevrier C; Institut de Neurosciences des Systèmes, Aix Marseille University, INSERM UMR 1106, 13005 Marseille, France.
  • Setti JL; Department of Clinical Pharmacology and Pharmacosurveillance, La Timone University Hospital; 13005 Marseille, France.
  • Jouve E; Institut de Neurosciences des Systèmes, Aix Marseille University, INSERM UMR 1106, 13005 Marseille, France.
  • Marsot A; University Hospital Timone, Department of Anaesthesiology and Critical Care Medicine, APHM, Aix Marseille University, 13005 Marseille, France.
  • Julian N; Department of Clinical Pharmacology and Pharmacosurveillance, La Timone University Hospital; 13005 Marseille, France.
  • Blin O; Institut de Neurosciences des Systèmes, Aix Marseille University, INSERM UMR 1106, 13005 Marseille, France.
  • Simeone P; Faculté de Pharmacie, Université de Montréal, Montreal, QC H3T 1J4, Canada.
  • Lagier D; University Hospital Timone, Department of Anaesthesiology and Critical Care Medicine, APHM, Aix Marseille University, 13005 Marseille, France.
  • Mokart D; Department of Clinical Pharmacology and Pharmacosurveillance, La Timone University Hospital; 13005 Marseille, France.
  • Bruder N; Institut de Neurosciences des Systèmes, Aix Marseille University, INSERM UMR 1106, 13005 Marseille, France.
  • Garnier M; University Hospital Timone, Department of Anaesthesiology and Critical Care Medicine, APHM, Aix Marseille University, 13005 Marseille, France.
  • Velly L; Inst Neurosci Timone, INT, CNRS, Aix Marseille University, UMR7289, 13005 Marseille, France.
Antibiotics (Basel) ; 12(8)2023 Aug 05.
Article en En | MEDLINE | ID: mdl-37627709
BACKGROUND: The aims of this study were to describe pharmacokinetic/pharmacodynamic target attainment in intensive care unit (ICU) patients treated with continuously infused ß-lactam antibiotics, their associated covariates, and the impact of dosage adjustment. METHODS: This prospective, observational, cohort study was performed in three ICUs. Four ß-lactams were continuously infused, and therapeutic drug monitoring (TDM) was performed at days 1, 4, and 7. The primary pharmacokinetic/pharmacodynamic target was an unbound ß-lactam plasma concentration four times above the bacteria's minimal inhibitory concentration during the whole dosing interval. The demographic and clinical covariates associated with target attainment were evaluated. RESULTS: A total of 170 patients were included (426 blood samples). The percentages of empirical ß-lactam underdosing at D1 were 66% for cefepime, 43% for cefotaxime, 47% for ceftazidime, and 14% for meropenem. Indexed creatinine clearance was independently associated with treatment underdose if increased (adjusted odds ratio per unit, 1.01; 95% CI, 1.00 to 1.01; p = 0.014) or overdose if decreased (adjusted odds ratio per unit, 0.95; 95% CI, 0.94 to 0.97; p < 0.001). Pharmacokinetic/pharmacodynamic target attainment was significantly increased after ß-lactam dosage adjustment between day 1 and day 4 vs. no adjustment (53.1% vs. 26.2%; p = 0.018). CONCLUSIONS: This study increases our knowledge on the optimization of ß-lactam therapy in ICU patients. A large inter- and intra-patient variability in plasmatic concentrations was observed, leading to inadequate exposure. A combined indexed creatinine clearance and TDM approach enables adequate dosing for better pharmacokinetic/pharmacodynamic target attainment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Etiology_studies / Observational_studies / Risk_factors_studies Idioma: En Revista: Antibiotics (Basel) Año: 2023 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Etiology_studies / Observational_studies / Risk_factors_studies Idioma: En Revista: Antibiotics (Basel) Año: 2023 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Suiza