Cefepime Daily Exposure and the Associated Impact on the Change in Sequential Organ Failure Assessment Scores and Vasopressors Requirement in Critically Ill Patients Using Repeated-Measures Mixed-Effect Modeling

Abstract

IMPORTANCE: Sepsis and septic shock are major healthcare problems that need early and appropriate management. OBJECTIVES: To evaluate the association of daily cefepime pharmacokinetic/pharmacodynamic (PK/PD) parameters with change in Sequential Organ Failure Assessment (SOFA) score and vasopressors requirement. DESIGN, SETTING, AND PARTICIPANTS: This is a retrospective study. Adult ICU patients who received cefepime for Gram-negative pneumonia or bloodstream infection (BSI) and had cefepime concentrations measured were included. Daily cefepime exposure was generated and PK/PD parameters calculated for patients. Repeated-measures mixed-effect modeling was used to evaluate the impact of PK/PD on the outcomes. MAIN OUTCOMES AND MEASURES: Change in daily SOFA score and vasopressors requirement. RESULTS: A total of 394 and 207 patients were included in the SOFA and vasopressors analyses, respectively. The mean (±sd) age was 55 years (19) and weight 81 kg (29). For the change in SOFA score, daily SOFA score, mechanical ventilation, renal replacement therapy, and number of vasopressors were included. In the vasopressors analysis, daily SOFA score, day of therapy, and hydrocortisone dose were significant covariates in the final model. Achieving cefepime concentrations above the minimum inhibitory concentration (MIC) (T>MIC) for 100% of the dosing interval was associated with 0.006 µg/kg/min decrease in norepinephrine-equivalent dose. Cefepime PK/PD did not have an impact on the daily change in SOFA score. CONCLUSIONS AND RELEVANCE: Achieving 100% T>MIC was associated with negligible decrease in vasopressors requirement in ICU patients with Gram-negative pneumonia and BSI. There was no impact on the change in SOFA score.