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Cefiderocol is an effective topical monotherapy for experimental extensively-drug resistant Pseudomonas aeruginosa

Eric G Romanowski1, Sonya M Mumper1, Hazel Q Shanks1

  • 1Charles T. Campbell Laboratory of Ophthalmic Microbiology, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

Biorxiv : the Preprint Server for Biology
|September 11, 2023
PubMed
Abstract

Insights

Cefiderocol effectively treated extensively drug-resistant Pseudomonas aeruginosa keratitis in rabbits. This new antibiotic shows promise for topical treatment of resistant bacterial eye infections.

Area of Science:

  • Ophthalmology
  • Infectious Diseases
  • Pharmacology

Background:

  • Antibiotic resistance in Pseudomonas aeruginosa poses a significant threat to ocular health.
  • Extensively drug-resistant (XDR) P. aeruginosa strains are increasingly prevalent, necessitating novel therapeutic agents.
  • Current topical treatments for bacterial keratitis may be limited by resistance patterns.

Approach:

  • Evaluated cefiderocol, a siderophore-cephalosporin, for topical monotherapy in experimental P. aeruginosa keratitis.
  • Assessed in vitro susceptibility using minimum inhibitory concentration (MIC) testing.
  • Determined in vivo efficacy, ocular toxicity, and corneal penetration in a rabbit keratitis model.

Key Points:

  • All P. aeruginosa keratitis isolates (n=135) were susceptible to cefiderocol, with a MIC90 of 0.125 μg/ml.
  • Topical cefiderocol (50 mg/ml) demonstrated minimal ocular toxicity and was well-tolerated in rabbits.
  • Cefiderocol significantly reduced corneal bacterial burden in vivo against an XDR P. aeruginosa isolate compared to ciprofloxacin and tobramycin.

Conclusions:

  • Cefiderocol is a well-tolerated and effective topical antibiotic against P. aeruginosa keratitis isolates in vitro and in vivo.
  • The drug achieved high corneal concentrations, exceeding the MIC90.
  • Cefiderocol represents a promising therapeutic option for managing keratitis caused by antibiotic-resistant P. aeruginosa.
Keywords:
Pseudomonas aeruginosaantibiotic resistancecefiderocolkeratitisocular infection

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