Ocular Microbiology and Immunology Group
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2023 OMIG Abstract

Cefiderocol Is a Safe and Effective Topical Monotherapy for Experimental Extensively-Drug Resistant Pseudomonas Aeruginosa Keratitis

Eric G. Romanowski¹, Kathleen A. Yates¹, Jonathan B. Mandell¹, Michael E. Zegans²,
and Robert M. Q. Shanks<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: The CDC recently reported a dangerous outbreak of eye infections linked to the use of artificial tears purchased online. Outbreak patients had serious corneal infections which led to blindness, loss of eyes, and even death. The infections were caused by an extensively drug resistant (XDR) Pseudomonas aeruginosa (PA) strain. This XDR PA strain (CDC1270) was resistant to all antibiotics except cefiderocol (CEF). This led us to the current study for which the goals were to determine the ocular toxicity/tolerability of topical CEF and its antibacterial efficacy against the XDR PA outbreak strain in NZW rabbit models.

Methods: Ocular Toxicity/Tolerability Study - Rabbits each were topically treated in both eyes with CEF 50, 25, 10, and 5 mg/ml solutions and Saline every 30 min for 6 h (13 total doses). Following treatment the eyes were examined and graded. Antibacterial Keratitis Model - Rabbits were inoculated with ~2300 CFU of CDC1270 intrastromally after the corneal epithelium was removed using an Amoils Epithelial Scrubber. 16 h post-inoculation the rabbits were divided into 5 groups (n=6): 1) CEF 50 mg/ml; 2) Ciprofloxacin 0.3% (CIP); 3) Tobramycin 14 mg/ml (TOB); 4) Saline (CON); and 5) No Treatment (Onset of Therapy CFU Control [ONSET]). Topical therapy for all groups was initiated at this time. The treatment regimen consisted of 1 drop every 15 min for 1 h, then every 30 min for 7 h (19 total doses over 8 h). Following treatment, the corneas were examined and harvested for CFU determinations.

Results: Ocular Toxicity/Tolerability - Topical CEF was non-toxic and well tolerated for all concentrations tested. Antibacterial Keratitis Model - Both CEF and TOB significantly reduced CDC1270 CFU compared to CON whereas CIP did not. CEF was also significantly more effective than both CIP and TOB in reducing CDC1270 corneal colony counts. CEF achieved a bactericidal (>99.9%) reduction compared to CON but not the ONSET group (>99%). TOB did not achieve a 99% decrease in CFU compared to the saline control group. Moreover, CEF sterilized 33% of the corneas compared to 0% for TOB and CIP.

Conclusions: Topical CEF 50 mg/ml was non-toxic and well tolerated in rabbit eyes and demonstrated antibacterial efficacy against an XDR PA strain in a NZW rabbit antibacterial keratitis model. Our results suggest that further development of CEF for use as a topical ophthalmic drop for treatment of XDR PA keratitis is warranted.

Disclosure: N, S (The Campbell Lab)

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