Dose individualization of Beta-lactam and fluoroquinolone antibiotics in ICU patients: to TDM or not to TDM and the effects on Outcome

Traditional antibiotic dosing is not designed for ICU patients. An 'one-dose-fits-all' approach is therefore likely to be inadequate, because the extreme pharmacokinetic behaviour of drugs in critically ill threatens the achievement of optimal antibiotic treatment. Moreover, ICU patients are at risk of developing infections with resistant micro-organisms, due to density of vulnerable patients and complexity of care. The aim of this trial is to evaluate a new early dosage adjustment strategy (TDM) of beta-lactam and fluoroquinolones in adult ICU patients to achieve the adequate pharmacodynamic targets (PDT), compared to the usual treatment strategy. Secondary aims are clinical outcome, the impact on antimicrobial resistance, and cost-effectiveness analyses between the TDM and non-TDM group.

- For each patient 2 separate blood samples are collected within 12-24 hours after first dose, to evaluate this new early dosage adjustment strategy. The first sample is taken at 50% of the dosing interval and the second (trough) 5-10 min prior to the next dose. Follow-up levels will be collected on day 2 (T=36-48h) after the initial first dose (after at least 2-4 subsequent doses of the newly adapted dosing regimen in the intervention group), and thereafter on day 5.

- Time Frame clinical data collection: 30d after inclusion

Assigned interventions in the active TDM group: dosage of beta-lactam and fluoroquinolone antibiotics will be adjusted according to serum concentrations. In the non-TDM (control) group samples of serum concentrations of beta-lactam and fluoroquinolone will be collected for comparison.