Pharmacokinetic variability of beta-lactams in critically ill patients: A narrative review.

The use of antibacterial drugs is very common in critically ill patients and beta-lactam agents are widely used in this context. Critically ill patients show several characteristics (e.g., sepsis, renal impairment or conversely augmented renal clearance, renal replacement therapy) that may alter beta-lactam pharmacokinetics (PK) in comparison with non-critically ill patients. This narrative literature review aims to identify recent studies quantifying the variability of beta-lactams volume of distribution and clearance and to determine its main determinants. Seventy studies published between 2000 and 2018 were retained. Data on volume of distribution and clearance variability were reported for 5 penicillins, 3 beta-lactamase inhibitors, 6 cephalosporins and 4 carbapenems. Data confirm specific changes in PK parameters and important variability of beta-lactam PK in critically ill patients. Renal function, body weight and use of renal replacement therapy are the principal factors influencing PK parameters described in this population. Few studies have directly compared beta-lactam PK in critically ill versus non-critically ill patients. Conclusions are also limited by small study size and sparse PK data in several studies. These results suggest approaches to assess this PK variability in clinical practice. Beta-lactam therapeutic drug monitoring seems to be the best way to deal with this issue.