Abstract

Cefiderocol is a new siderophore-cephalosporin for the treatment of multi-drug resistant Gram-negative pathogens. As a reserve agent, it will and should be used primarily in critically ill patients in the upcoming years. Due to the novelty of the substance little data on the pharmacokinetics in critically ill patients with septic shock and renal failure (including continuous renal replacement therapy and cytokine adsorber therapy) is available. We performed therapeutic drug monitoring in a cohort of five patients treated with cefiderocol, to improve the knowledge on pharmacokinetics in this vulnerable patient population. As expected for a cephalosporin with predominantly renal elimination the maintenance dose could be reduced in patients with renal impairment or on continuous renal replacement therapy. The manufacturer’s dosing instructions were sufficient to achieve a drug level well above the MIC. However, the addition of a cytokine adsorber might reduce serum levels substantially, so that in this context therapeutic drug monitoring and dose adjustment are recommended.

Highlights

  • IntroductionCefiderocol is a novel siderophore-cephalosporin, with broad activity against multidrug resistant (MDR) Enterobacterales and non-fermenting Gram-negative bacteria like

  • Cefiderocol is a novel siderophore-cephalosporin, with broad activity against multidrug resistant (MDR) Enterobacterales and non-fermenting Gram-negative bacteria likePseudomonas aeruginosa, Acinetobacter baumannii or Stenotrophomonas maltophilia

  • The patient was transferred to the intensive care unit (ICU) for non-invasive ventilation and intravenous treprostinil therapy

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Summary

Introduction

Cefiderocol is a novel siderophore-cephalosporin, with broad activity against multidrug resistant (MDR) Enterobacterales and non-fermenting Gram-negative bacteria like. Pseudomonas aeruginosa, Acinetobacter baumannii or Stenotrophomonas maltophilia. This novel antibiotic drug, showed potent in-vitro activity against over 90% of meropenem-resistant. By the addition of a catechol side-chain cefiderocol gains the ability to act as a siderophore [4]. This facilitates the drug’s active transport into the bacterial cell and protects it from efflux mechanisms [5]. There is currently limited data on the clinical use of cefiderocol against MDR Gram-negative bacteria in critically ill patients. Cefiderocol shows linear pharmacokinetics with a half-life (t1/2 ) of 2–2.7 h and a drug clearance (CL)

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