Article Text

Download PDFPDF
Physicochemical stability of cefiderocol, a novel siderophore cephalosporin, in syringes at 62.5 mg/mL for continuous administration in intensive care units
  1. Guillaume Loeuille1,
  2. Jean Vigneron1,2,
  3. Elise D'Huart1,2,
  4. Alexandre Charmillon3,
  5. Béatrice Demoré1,4
  1. 1Pharmacy, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-lès-Nancy, France
  2. 2Non-Profit Association, INFOSTAB, Heillecourt, 54180, France
  3. 3Service de Maladies Infectieuses, Centre Hospitalier Régional Universitaire de Nancy, Vandoeuvre-lès-Nancy, 54511, France
  4. 4EA 4360 APEMAC, Université de Lorraine, Nancy, Lorraine, France
  1. Correspondence to Dr Jean Vigneron, Pharmacy Department, Centre Hospitalier Universitaire de Nancy, Vandoeuvre-lès-Nancy, 54511, France; j.vigneron{at}chru-nancy.fr

Abstract

Introduction Cefiderocol is a new siderophore time-dependent antibiotic of last resort. The manufacturer reports a stability of 6 hours for the infusion solution diluted in normal saline (NS) or dextrose 5% in water (D5W) for a concentration between 7.5 and 20 mg/mL. Optimising its effectiveness by continuous infusion is crucial. The aim of this work was to study the physicochemical stability of cefiderocol diluted in NS or D5W in polypropylene syringes for 48 hours at a concentration of 62.5 mg/mL stored at room temperature, protected or not from light.

Materials and methods Three preparations for each condition were performed. At each time of the analysis, one sample for each preparation was analysed in triplicate by a validated high performance liquid chromatography method coupled to a photodiode array detector at 260 nm. Particle contamination, absorbance measurement, visual inspection and pH measurement were assessed. The limit of stability was set at 90% of the initial concentration, without physical modification.

Results The linearity was validated with an R² of 0.9999. The coefficients of variation for repeatability and intermediate precision were less than 2%. In NS and D5W, cefiderocol retained more than 90% of the initial concentration after 12 hours in syringes, exposed or not to light. Two degradation products (nos 2 and 11, observed during forced degradation) were detected during the stability study. The absorbance at 410 nm increased progressively, regardless of the storage conditions. The particulate contamination test met the specifications of the container. pH values were all between 5.22 and 5.32. No visual changes were detected.

Conclusion In polypropylene syringes, cefiderocol 62.5 mg/mL (3 g in 48 mL) diluted in NS or D5W was stable for 12 hours at room temperature. These new data allow the use of cefiderocol in continuous infusion.

  • critical care
  • administration
  • intravenous
  • pharmaceutical preparations
  • microbiology
  • microbiology

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

Statistics from Altmetric.com

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

View Full Text

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.