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Clinical Pharmacokinetics and Pharmacodynamics of Cefepime

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Abstract

Cefepime is a broad-spectrum fourth-generation cephalosporin with activity against Gram-positive and Gram-negative pathogens. It is generally administered as an infusion over 30–60 min or as a prolonged infusion with infusion times from 3 h to continuous administration. Cefepime is widely distributed in biological fluids and tissues with an average volume of distribution of ~ 0.2 L/kg in healthy adults with normal renal function. Protein binding is relatively low (20%), and elimination is mainly renal. About 85% of the dose is excreted unchanged in the urine, with an elimination half-life of 2–2.3 h. The pharmacokinetics of cefepime is altered under certain pathophysiological conditions, resulting in high inter-individual variability in cefepime volume of distribution and clearance, which poses challenges for population dosing approaches. Consequently, therapeutic drug monitoring of cefepime may be beneficial in certain patients including those who are critically ill, have life-threatening infections, or are infected with more resistant pathogens. Cefepime is generally safe and efficacious, with a goal exposure target of 70% time of the free drug concentration over the minimum inhibitory concentration for clinical efficacy. In recent years, reports of neurotoxicity have increased, specifically in patients with impaired renal function. This review summarizes the pharmacokinetics, pharmacodynamics, and toxicodynamics of cefepime contemporarily in the setting of increasing cefepime exposures. We explore the potential benefits of extended or continuous infusions and therapeutic drug monitoring in special populations.

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Authors and Affiliations

  1. Department of Pharmacy Practice, Chicago College of Pharmacy, Midwestern University, 555 31st St., Downers Grove, IL, 60515, USA

    Gwendolyn M. Pais, Jack Chang & Marc H. Scheetz

  2. Chicago College of Pharmacy Pharmacometrics Center of Excellence, Midwestern University, Downers Grove, IL, USA

    Gwendolyn M. Pais, Jack Chang & Marc H. Scheetz

  3. Department of Pharmacy, Mayo Clinic, Rochester, MN, USA

    Erin F. Barreto

  4. Center for Clinical Pharmacology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Gideon Stitt & Kevin J. Downes

  5. Division of Infectious Diseases, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Kevin J. Downes

  6. Department of Pediatrics, The University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

    Kevin J. Downes

  7. Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, USA

    Mohammad H. Alshaer

  8. Infectious Disease Pharmacokinetics Lab, Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA

    Mohammad H. Alshaer

  9. College of Graduate Studies, Midwestern University, Downers Grove, IL, USA

    Emily Lesnicki

  10. Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL, USA

    Vaidehi Panchal

  11. Division of Neurology, College of Medicine, University of Florida, Gainesville, FL, USA

    Maria Bruzzone

  12. Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL, USA

    Argyle V. Bumanglag & Sara N. Burke

  13. Cognitive Aging and Memory Center, College of Medicine, University of Florida, Gainesville, FL, USA

    Argyle V. Bumanglag & Sara N. Burke

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  1. Gwendolyn M. Pais
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  2. Jack Chang
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Correspondence to Marc H. Scheetz.

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Funding

This review received no specific grant from any funding agency. Erin F. Barreto is supported by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health under Award Number K23AI143882 (PI; EFB). Gideon Stitt is supported by a National Institute of Child Health & Human Development (NICHD)-funded postdoctoral fellowship (T32GM008562). Kevin J. Downes is supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) of the National Institutes of Health under Award Number K23HD091365. Kevin J. Downes has received research support from Merck & Co., Inc. unrelated to the current work. The funding sources had no role in data collection, interpretation; writing the report; or the decision to submit the report for publication. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIAID, NICHD, or NIH.

Conflicts of interest/Competing interests

Marc H. Scheetz reports a research contract with Allecra. Kevin J. Downes receives research support from Merck, Inc., unrelated to the current project. Erin F. Barreto is a consultant for FAST Biomedical and Wolters Kluwer, unrelated to the current project. All other authors have no other related conflicts of interest to declare.

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Pais, G.M., Chang, J., Barreto, E.F. et al. Clinical Pharmacokinetics and Pharmacodynamics of Cefepime. Clin Pharmacokinet 61, 929–953 (2022). https://doi.org/10.1007/s40262-022-01137-y

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