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Cefiderocol and Moxifloxacin Have Additive and Synergistic Activity Against Pseudomonas aeruginosa Including an

Eric G Romanowski1, Brennan M Schilling2, Emily K Young1

  • 1Charles T. Campbell Laboratory, Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.

Investigative Ophthalmology & Visual Science
|November 12, 2025
PubMed
Abstract

Insights

Cefiderocol and moxifloxacin show synergy against drug-resistant Pseudomonas aeruginosa keratitis. This combination offers a promising new treatment for challenging ocular infections caused by resistant bacteria.

Area of Science:

  • Ophthalmology
  • Infectious Diseases
  • Microbiology

Background:

  • The 2023 Pseudomonas aeruginosa keratitis outbreak highlighted the urgent need for novel treatments against multi-drug-resistant (MDR) and extensively drug-resistant (XDR) bacteria.
  • Increased prevalence of lasR mutant keratitis isolates necessitates understanding quorum-sensing defects' impact on antibiotic efficacy.

Purpose of the Study:

  • To evaluate the in vitro efficacy and synergistic potential of cefiderocol and moxifloxacin against P. aeruginosa keratitis isolates.
  • To assess the influence of quorum-sensing defects on the efficacy of this antibiotic combination.
  • To compare cefiderocol-moxifloxacin synergy with ceftazidime-moxifloxacin, using ceftazidime as a comparator lacking cefiderocol's iron-binding entry mechanism.

Main Methods:

  • Time-kill assays and epsilometer (E-test) were employed to determine minimum inhibitory concentrations (MICs) and drug interactions.
  • Fractional inhibitory concentration indices (FICI) were calculated to classify interactions as antagonistic, indifferent, additive, or synergistic.
  • Quorum-sensing defective strains were identified via a characteristic colony sheen phenotype linked to LasR system defects.

Main Results:

  • Consistent synergistic interactions between cefiderocol and moxifloxacin were observed in time-kill studies against all seven tested P. aeruginosa keratitis isolates, including one from the 2023 outbreak.
  • E-test assays revealed additive or synergistic activity in 79% of isolates, decreasing to 60% in suspected quorum-sensing defective strains.
  • The ceftazidime-moxifloxacin combination demonstrated reduced efficacy, especially against sheen-positive strains. Cefiderocol-moxifloxacin showed indifferent effects against Serratia marcescens and Staphylococcus aureus.

Conclusions:

  • Cefiderocol and moxifloxacin exhibit significant in vitro synergy against the majority of tested P. aeruginosa keratitis isolates, even those with quorum-sensing defects.
  • This combination warrants further investigation as a potential therapeutic strategy for managing highly drug-resistant ocular infections.

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