Applying Cefepime Population Pharmacokinetics to Critically Ill Patients Receiving Continuous Renal Replacement...

Patients admitted to the intensive care unit (ICU) may need continuous renal replacement therapy (CRRT) due to acute kidney injury or worsening of underlying chronic kidney disease. This will affect their antimicrobial exposure and may have a significant impact on the treatment. We aim to develop a cefepime pharmacokinetic (PK) model in CRRT ICU patients and generate the posterior predictions for a group and assess their therapy outcomes. Adult patients, who were admitted to the ICU, received cefepime, and had its concentration measured while on CRRT were included from three different data sets. In two data sets, samples were collected from the predialyzer, postdialyzer ports, and effluent fluid at different times within the same dosing interval. The third data set had only cefepime plasma concentration measured as part of clinical service. Patients' demographics, cefepime regimens and concentration, CRRT parameters, and therapy outcomes were recorded. NPAG was used for population PK and posterior predictions. A total of 125 patients were included. Cefepime was described by a five-compartment model, and the CRRT flow rates described the rates of cefepime transfer between compartments. The posterior predictions were generated for the third data set and the median (range) fT_>MIC was 100% (27%-100%) and fT_>4×MIC was 64% (0%-100%). The mortality rate was 53%. There was no difference in target attainment in terms of clinical cure and 30-day mortality. This model can be used as a precision dosing tool in CRRT patients. Future studies may address other PK/PD targets in a larger population.