In this episode, I’ll discuss an article about the pharmacokinetic and pharmacodynamic properties of IV push cefepime in critically ill patients with sepsis.
IV push cefepime has become a desirable method of administration, but data on the pharmacokinetic and pharmacodynamic properties of this administration technique in critically ill patients has been up until this point, limited. However a group of authors published in Pharmacotherapy a prospective observational study to characterize the PK profile and PD target attainment of IVP cefepime in critically ill patients with sepsis.
17 hospitalized adult patients receiving IVP cefepime were included, all of whom had a central or midline catheter, an intensive care unit (ICU) length of stay of at least 48 hours, creatinine clearance above 30 mL/min without renal replacement therapy, and a diagnosis of sepsis. In all patients the authors measured serum concentrations at cefepime steady state immediately before and at 5, 15, 30, 60, 120, and 240 min after a dose.
Pharmacokinetic analysis of the results showed area under the curve similar to what is achieved in patients who receive cefepime by intermittent infusion. The volume of distrubution and half-life were consistent with what is expected in patients who are critically ill.
There was considerable interpatient variability noted in the cefepime trough concentrations. The median trough value was higher than historical intermittent infusion data, but there was a wide range that included some trough concentrations that fell below what is considered optimal.
Treatment failure was defined as a composite of escalation of antibiotics or in-hospital mortality, and this occurred in 6 of the 17 patients for a rate of 35%. This is higher than previous rates in retrospective studies performed at the same institution with intermittent infusions.
The authors concluded:
Intravenous push cefepime in critically ill patients achieved systemic exposure comparable to traditional intermittent infusion but demonstrated substantial interpatient PK variability. These findings highlight the impact of critical illness on cefepime disposition and support further evaluation of personalized cefepime dosing for the ICU population.
This is a relatively small study but the high interpatient variability is concerning and the switch to IVP cefepime that occurred in many institutions due to shortages of small volume solutions or desired for more rapid administration may require further study before it is considered acceptable as routine practice.
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