Ocular Microbiology and Immunology Group
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2025 OMIG Abstract

Combating Multidrug-Resistant Pseudomonas Aeruginosa Keratitis: In vitro Synergy Between Cefiderocol and Moxifloxacin

Eric G. Romanowski¹, Brennan M. Schilling², Emily K. Young¹, Sonya M. Mumper¹, 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, Pennsylvania; ²Geisel School of Medicine at Dartmouth, Hanover, New Hampshire

Purpose: In 2023 an outbreak of extensively drug resistant Pseudomonas aeruginosa keratitis was linked to contaminated artificial tears which led to wide-spread loss of vision without an adequate therapy. This highlighted the need for new treatments targeting ocular infections caused by multi-drug and extensively drug-resistant bacteria. We previously demonstrated that antibiotic cefiderocol may be an effective therapy for keratitis caused by extensively drug-resistant P. aeruginosa. The current study took this premise further by evaluating the in vitro efficacy and potential synergy of a combination of cefiderocol and moxifloxacin against P. aeruginosa keratitis isolates.

Methods: Time-kill and epsilometer (E-test) assays were used to determine minimum inhibitory concentrations (MIC) and drug interactions between cefiderocol and moxifloxacin for P. aeruginosa keratitis isolates. A >2-Log₁₀ decrease in colony counts compared to the inoculum and lowest count out of either drug alone at 24 hours was considered a synergistic effect in time-kill assays. Similarly, a >1 but <2 Log₁₀ decrease in colony counts was considered an additive effect. Fractional inhibitory concentration indices were calculated to characterize drug interactions as antagonistic, indifferent, additive, or synergistic for E-Test studies.

Results: Time-kill studies demonstrated consistent synergistic interactions between cefiderocol and moxifloxacin against 7/7 (100%) of tested P. aeruginosa keratitis isolates, including the extensively drug-resistant isolate from the 2023 outbreak. E-test based assays showed additive or synergistic activity against 79% of P. aeruginosa isolates (n=39).

Conclusions: These findings demonstrate in vitro synergy between cefiderocol and moxifloxacin against most tested P. aeruginosa keratitis isolates. This combination therapy could potentially be developed for management of highly antibiotic-resistant P. aeruginosa ocular infections.