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

Mohammad H Alshaer; Roy Williams; Mays J Mousa; Kaitlin M Alexander; Kelly L Maguigan; Kayihura Manigaba; Nicole Maranchick; Bethany R Shoulders; Timothy W Felton; Sumith K Mathew; Charles A Peloquin

doi:10.1097/CCE.0000000000000993

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

Crit Care Explor. 2023 Oct 27;5(11):e0993. doi: 10.1097/CCE.0000000000000993. eCollection 2023 Nov.

Authors

Mohammad H Alshaer^{1

2}, Roy Williams², Mays J Mousa¹, Kaitlin M Alexander^{2

3}, Kelly L Maguigan³, Kayihura Manigaba², Nicole Maranchick^{1

2}, Bethany R Shoulders^{2

3}, Timothy W Felton^{4

5}, Sumith K Mathew⁶, Charles A Peloquin^{1

2}

Affiliations

¹ Infectious Disease Pharmacokinetics Laboratory, Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL.
² Emerging Pathogens Institute, University of Florida, Gainesville, FL.
³ Department of Pharmacy, UF Health Shands Hospital, Gainesville, FL.
⁴ North West Ventilation Unit, Manchester University NHS Foundation Trust, Manchester, United Kingdom.
⁵ Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom.
⁶ Department of Pharmacology and Clinical Pharmacology, Christian Medical College, Vellore, India.

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.

Keywords: cefepime; critical care; organ dysfunction scores; pharmacokinetics; vasoconstrictor agents.

Abstract

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