Feasibility of Continuous Infusion of Cefiderocol in Conjunction with the Establishment of Therapeutic Drug Monitoring in Patients with Extensively Drug-Resistant Gram-Negative Bacteria

Clin Drug Investig. 2023 Apr;43(4):307-314. doi: 10.1007/s40261-023-01257-8. Epub 2023 Apr 5.

Abstract

Background and objective: Resistance to antibacterial substances is a huge and still emerging issue, especially with regard to Gram-negative bacteria and in critically ill patients. We report a study in six patients infected with extensively drug-resistant Gram-negative bacteria in a limited outbreak who were successfully managed with a quasi-continuous infusion of cefiderocol.

Methods: Patients were initially treated with prolonged infusions of cefiderocol over 3 h every 8 h, and the application mode was then switched to a quasi-continuous infusion of 2 g over 8 h, i.e. 6 g in 24 h. Therapeutic drug monitoring (TDM) was established using an in-house liquid chromatography-tandem mass spectrometry (LC-MS/MS) method.

Results: Determined trough plasma concentrations were a median of 50.00 mg/L [95% confidence interval (CI) 27.20, 74.60] and steady-state plasma concentrations were a median of 90.96 mg/L [95% CI 37.80, 124]. No significant differences were detected with respect to acute kidney injury/continuous renal replacement therapy. Plasma concentrations determined from different modes of storage were almost equal when frozen or cooled, but markedly reduced when stored at room temperature.

Conclusions: (Quasi) continuous application of cefiderocol 6 g/24 h in conjunction with TDM is a feasible mode of application; the sample for TDM should either be immediately analyzed, cooled, or frozen prior to analysis.

MeSH terms

  • Anti-Bacterial Agents / therapeutic use
  • Cefiderocol
  • Chromatography, Liquid
  • Drug Monitoring*
  • Feasibility Studies
  • Gram-Negative Bacteria
  • Humans
  • Tandem Mass Spectrometry*

Substances

  • Anti-Bacterial Agents