Therapeutic drug monitoring of carbapenem antibiotics in critically ill patients: an overview of principles, recommended dosing regimens, and clinical outcomes

The importance of antibiotic treatment for sepsis in critically ill septic patients is well established. Consistently achieving the dose of antibiotics required to optimally kill bacteria, minimize the development of resistance, and avoid toxicity is challenging. The increasing understanding of the pharmacokinetic and pharmacodynamic (PK/PD) characteristics of antibiotics, and the effects of critical illness on key PK/PD parameters, is gradually re-shaping how antibiotics are dosed in critically ill patients.The PK/PD characteristics of commonly used carbapenem antibiotics, the principles of the application of therapeutic drug monitoring (TDM), and current as well as future methods of utilizing TDM to optimally devise dosing regimens will be reviewed. The limitations and evidence-base supporting the use of carbapenem TDM to improve outcomes in critically ill patients will be examined.It is important to understand the principles of TDM in order to correctly inform dosing regimens. Although the concept of TDM is attractive, and the ability to utilize PK software to optimize dosing in the near future is expected to rapidly increase clinicians' ability to meet pre-defined PK/PD targets more accurately, current evidence provides only limited support for the use of TDM to guide carbapenem dosing in critically ill patients.