Daptomycin Pharmacokinetics and Pharmacodynamics in Septic and Critically Ill Patients

Infections, including sepsis, are associated with high mortality rates in critically ill patients in the intensive care unit (ICU). Appropriate antibiotic selection and adequate dosing are important for improving patient outcomes. Daptomycin is bactericidal in bloodstream infections caused by Staphylococcus aureus and other Gram-positive pathogens cultured in ICU patients. The drug has concentration-dependent activity, and the area under the curve/minimum inhibitory concentration ratio is the pharmacokinetic/pharmacodynamic (PK/PD) index that best correlates with daptomycin activity, whereas toxicity correlates well with daptomycin plasma trough concentrations (or minimum concentration [C-min]). Adequate daptomycin exposure can be difficult to achieve in ICU patients; multiple PK alterations can result in highly variable plasma concentrations, which are difficult to predict. For this reason, therapeutic drug monitoring could help clinicians optimize daptomycin dosing, thus improving efficacy while decreasing the likelihood of serious adverse events. This paper reviews the literature on daptomycin in ICU patients with sepsis, focusing on dosing and PK and PD parameters.