Ensuring target concentrations of antibiotics in critically ill patients through dose adjustment

Antibiotics are commonly prescribed in critical care, and given the large variability of pharmacokinetic (PK) parameters in these patients, drug PK frequently varies during therapy with the risk of either treatment failure or toxicity. Therefore, adequate antibiotic dosing in critically ill patients is very important.

This review provides an overview of the basic principles of PK and pharmacodynamics of antibiotics and the main patient and pathogen characteristics that may affect the dosage of antibiotics and different approaches to adjust doses.

Dose adjustment should be done for aminoglycosides and glycopeptides based on daily drug concentration monitoring. For glycopeptides, in particular vancomycin, the residual concentration (Cres) should be assessed daily. For beta-lactam antibiotics, a loading dose should be administered, followed by three different possible approaches, as TDM is rarely available in most centers: 1) antibiotic regimens should be adapted according to renal function and other risk factors; 2) nomograms or software can be used to calculate daily dosing; 3) TDM should be performed 24-48 h after the initiation of treatment; however, the results are required within 24 hours to appropriately adjust dosage regimens. Drug dosing should be reduced or increased according to the TDM results.