<i>β</i>-Lactam Pharmacokinetic/Pharmacodynamic Target Attainment in Intensive Care Unit Patients: A Prospective, Observational, Cohort Study

• Main Authors: Romain Guilhaumou (Author), Constance Chevrier (Author), Jean Loup Setti (Author), Elisabeth Jouve (Author), Amélie Marsot (Author), Nathan Julian (Author), Olivier Blin (Author), Pierre Simeone (Author), David Lagier (Author), Djamel Mokart (Author), Nicolas Bruder (Author), Marc Garnier (Author), Lionel Velly (Author)
• Format: Book
• Published: MDPI AG, 2023-08-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Background: The aims of this study were to describe pharmacokinetic/pharmacodynamic target attainment in intensive care unit (ICU) patients treated with continuously infused <i>ß</i>-lactam antibiotics, their associated covariates, and the impact of dosage adjustment. Methods: This prospective, observational, cohort study was performed in three ICUs. Four <i>ß</i>-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 <i>ß</i>-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 <i>ß</i>-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; <i>p</i> = 0.014) or overdose if decreased (adjusted odds ratio per unit, 0.95; 95% CI, 0.94 to 0.97; <i>p</i> < 0.001). Pharmacokinetic/pharmacodynamic target attainment was significantly increased after <i>ß</i>-lactam dosage adjustment between day 1 and day 4 vs. no adjustment (53.1% vs. 26.2%; <i>p</i> = 0.018). Conclusions: This study increases our knowledge on the optimization of <i>ß</i>-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.

Item Description

10.3390/antibiotics12081289
2079-6382