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2023 OMIG Abstract

Cefiderocol Solution Is Stable at Refrigeration Temperature and Produces High Concentrations in Rabbit Corneas After Topical Therapy

Kathleen A. Yates¹, Jonathan B. Mandell¹, Michael E. Zegans², Robert M. Q. Shanks¹,
and Eric G. Romanowski<sup>1

1</sup>The Charles T. Campbell Ophthalmic Microbiology Laboratory, Department of Ophthalmology,
University of Pittsburgh School of Medicine, Pittsburgh, PA; ²Geisel School of Medicine at Dartmouth, Hanover, NH

Purpose: To determine the stability of 50 mg/ml solutions of Cefiderocol (CEF), a new potential antibiotic for the topical treatment of extensively drug resistant (XDR) Pseudomonas aeruginosa (PA) keratitis. In addition, we wished to determine the approximate corneal CEF concentrations from rabbit corneas treated with CEF 50 mg/ml and infected with a typical antibiotic-susceptible PA and the XDR PA.

Methods: CEF Stability Study - The stability of the topical 50 mg/ml concentrations of CEF was determined using a bioassay comparing the sizes of zones of inhibition produced from dilutions of previously prepared and refrigerated 50 mg/ml CEF solutions (33, 27, 21, and 7 days earlier) and kept out of light to those from a freshly prepared solution. Approximate Corneal Concentrations - To determine approximate CEF corneal concentrations, corneas (with the corneal epithelium removed) from the PA rabbit keratitis studies were used. Following homogenizing and processing of the corneal buttons for colony counts, the supernatants of the homogenates were centrifuged and filtered to remove the live bacteria. The corneal samples and freshly prepared CEF standard concentrations were used in the bioassay. The zone sizes of the corneal homogenates were inserted into a concentration equation produced using a Linear Fitted Line Plot Regression Analysis of CEF concentration vs. zone size for the CEF standards to determine the corneal concentrations.

Results: CEF Stability Study - The antibacterial zone sizes for all CEF concentrations and refrigeration times were indistinguishable over 33 days. Approximate Corneal Concentrations - The mean and standard deviation CEF concentration obtained from the corneal homogenates from eyes infected with PA was 23.88 ± 8.69 µg/ml. The concentrations ranged from 12.53 µg/ml to 38.58 µg/ml per cornea.

Conclusions: CEF 50 mg/ml solutions do not appear to lose bioactivity for up to 33 days when refrigerated and kept out of light. Corneas infected with a typical antibiotic-susceptible PA and the XDR PA following topical CEF 50 mg/ml treatment had a mean CEF corneal concentration that was 191x greater than the MIC₉₀ (0.125 µg/ml) of the PA keratitis isolates tested, including the XDR PA isolate (0.125 µg/ml). These results indicate that a CEF 50 mg/ml solution could be used for several days when properly stored and can achieve high corneal concentrations when being used as a potential fortified antibiotic to topically treat XDR PA keratitis.

Disclosure: N, S (The Campbell Lab)

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