Mortality in critically ill patients with infection is a global health problem. Traditional antibiotic dosing is not designed for the complexity of critically ill intensive care unit (ICU) patients. Sub optimal dosing will lead to longer ICU and hospital stay and eventually higher health costs.
,A 'one-dose-fits-all' approach seems inadequate to reach the pharmacodynamic target in ICU patients. Therapeutic drug monitoring(TDM), determination of drug levels with the application of pharmacokinetic and pharmacodynamic principles to optimize dosage regimens, is likely to increase reachment of pharmacodynamic target. Beta-lactam antibiotics are the cornerstones of anti-infective therapy on the ICU. In several international studies it has been shown that beta-lactams are highly underdosed in ICU patients and we have found similar results in our EXPAT study.
Given the problems described above, it is surprising that dose individualization of beta-lactams is hardly practised. However, randomized controlled clinical studies with primary patient outcomes showing the benefit of TDM are lacking so far.
We propose a randomized study comparing active TDM versus standard dosing of beta-lactams. The study is performed in 5 large hospitals, 422 patients will be included receiving antibiotics, according to standard clinical care. Blood levels of antibiotics are determined at defined time points and are combined with microbiology data to set an individualized TDM advise for the individual ICU patient in the active TDM group. In the standard group blood levels will be analyzed in bulk later.
Primary objective: To show that the length of stay at the ICU decreases significantly in the group with active TDM (intervention group) in comparison to the group with no TDM (control group). Length of IC stay is associated with less mortality and less post-IC syndrome.
Secondary objectives; to show that active TDM results in improved clinical outcome, cost-effectiveness and quality of life