Kathryn Pavia, MD
Cincinnati Childrens Hospital Medical Center
Cincinnati, Ohio
Disclosure information not submitted.
Sonya Tang Girdwood, MD, PhD
Assistant Professor
Cincinnati Children's Hospital Medical Center, United States
Disclosure information not submitted.
Peter Tang, PhD
Associate Professor
Cincinnati Children's Hospital Medical Center, United States
Disclosure information not submitted.
Calise Curry
Clinical Research Coordinator
Cincinnati Children's Hospital Medical Center, United States
Disclosure information not submitted.
Rhonda Jones
Research Nurse
Cincinnati Children's Hospital Medical Center, United States
Disclosure information not submitted.
Erin Stoneman
Clinical Research Coordinator
Cincinnati Children's Hospital Medical Center, Ohio, United States
Disclosure information not submitted.
Toni Yunger
Clinical Research Coordinator
Cincinnati Children's Hospital Medical Center, United States
Disclosure information not submitted.
Min Dong, PhD
Assistant Professor
Cincinnati Children's Hospital Medical Center, United States
Disclosure information not submitted.
Alexander Vinks, PharmD, PhD, FCP
Professor, Division Director
Cincinnati Children's Hospital Medical Center, United States
Disclosure information not submitted.
Jennifer Kaplan, MD, MS, FCCM
Professor, Attending Physician
Cincinnati Children's Hospital Medical Center, United States
Disclosure information not submitted.
Title: Impaired Renal Function is Associated with High Cefepime Concentrations in Critically Ill Children
Introduction: Cefepime (FEP) is one of the most commonly used antibiotics for critically ill children. We sought to characterize critically ill patients with elevated FEP trough concentrations with a focus on the impact of renal function on pharmacokinetics.
Methods: An IRB approved prospective study was conducted at a tertiary care children’s hospital. Patients who had at least 1 FEP dose administered in the PICU and had concentrations measured by opportunistic sampling were enrolled. Total FEP concentrations were measured using a validated high performance liquid chromatography assay. Trough samples were those collected within 1h of the next expected dose, and elevated troughs were defined as ≥30µg/mL based on adult toxicity studies. Demographics and clinical characteristics were compared using Mann-Whitney rank sum tests for continuous and Chi-square analysis for categorical data.
Results: Fifty eight patients (282 samples) were included, of which 34 patients had troughs (67 samples). Six patients had at least one FEP trough ≥30µg/mL (12 samples). Patients with and without elevated troughs were similar in age, weight, sex, hospital LOS, and duration of FEP therapy. Patients with elevated troughs compared to non-elevated troughs had lower baseline creatinine clearance (median 73 mL/min/1.73m2 [IQR 15-135] vs 143 [IQR 100-187], p=0.01) and higher frequency of renal replacement therapy (RRT) during study (50% vs 7%, p< 0.001). There was no difference in mortality between groups. Of the 6 patients with elevated troughs, 3 had undergone solid organ transplants (2 kidney, 1 multivisceral) >6 mos prior, 1 had a kidney transplant 5 days prior to inclusion, 1 had liver failure listed for transplant, and 1 was previously healthy with meningococcemia. Three of the 6 patients were started and maintained on reduced FEP dose or frequency.
Conclusions: Elevated FEP troughs occur in patients with impaired renal function including those receiving RRT and those already getting reduced FEP dosing. Future work will use pharmacokinetic modeling to quantify FEP exposure during the dosing cycle and identify clinical implications of increased drug exposure.