Enhanced Efficacy of Cefiderocol With PolyTrim Combination Therapy in a Rabbit Model of Extensively Drug-Resistant

Eric G Romanowski1, Emily K Young1, Jonathan B Mandell1

  • 1The Charles T. Campbell Ophthalmic Microbiology Laboratory, UPMC Vision Institute, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States.

Abstract

Insights

The combination of cefiderocol (FDC) with PolyTrim (PT) effectively treated Pseudomonas aeruginosa keratitis in rabbits, sterilizing corneas and preventing spread. This FDC + PT therapy shows promise for extensively drug-resistant bacterial eye infections.

Area of Science:

  • Ophthalmology
  • Microbiology
  • Pharmacology

Background:

  • The 2023 Pseudomonas aeruginosa keratitis outbreak highlighted the urgent need for novel therapies against drug-resistant ocular pathogens.
  • In vitro studies suggested cefiderocol (FDC) combined with moxifloxacin (MOX) or polymyxin B sulfate (PB) may be effective.

Purpose of the Study:

  • To evaluate the in vivo efficacy of combining cefiderocol (FDC) with commercial formulations of moxifloxacin (MOX) or PolyTrim (PT) for treating Pseudomonas aeruginosa keratitis.

Main Methods:

  • New Zealand White rabbits with intrastromal Pseudomonas aeruginosa infections were treated with FDC combined with MOX or PT.
  • Treatments were administered every 30 minutes for 8 hours, followed by bacterial burden assessment (CFU/cornea) and anterior chamber cultures.

Main Results:

  • The FDC + PT combination achieved a 6.9 log10 reduction in bacterial burden and sterilized 10 of 12 corneas, significantly outperforming monotherapies and FDC + MOX.
  • FDC-containing treatments prevented anterior chamber invasion, and FDC or PT treatments prevented corneal perforations.

Conclusions:

  • The combination of cefiderocol and PolyTrim (FDC + PT) demonstrated superior efficacy in treating Pseudomonas aeruginosa keratitis.
  • FDC + PT is a promising therapeutic strategy for extensively drug-resistant Pseudomonas aeruginosa keratitis, offering sterilization and protection against intraocular spread and perforation.

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