Background: The aims of this study were to describe pharmacokinetic/pharmacodynamic target attainment in intensive care unit (ICU) patients treated with continuously infused -lactam antibiotics, their associated covariates, and the impact of dosage adjustment.

Methods: This prospective, observational, cohort study was performed in three ICUs. Four -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 -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 -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; = 0.014) or overdose if decreased (adjusted odds ratio per unit, 0.95; 95% CI, 0.94 to 0.97; < 0.001). Pharmacokinetic/pharmacodynamic target attainment was significantly increased after -lactam dosage adjustment between day 1 and day 4 vs. no adjustment (53.1% vs. 26.2%; = 0.018).

Conclusions: This study increases our knowledge on the optimization of -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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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10451857PMC
http://dx.doi.org/10.3390/antibiotics12081289DOI Listing

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