Evidence map›Paper›PMID 41222194›Full record

ArticleTranslational vision science & technology2025

Combination Therapy of Cefiderocol and Polymyxin B Against Pseudomonas aeruginosa Keratitis Isolates In Vitro.

Eric G Romanowski, Emily K Young, Sonya M Mumper, Kathleen A Yates, Rachel A F Wozniak, Michael E Zegans, Robert M Q Shanks

Abstract read
In one paragraph

Article in Translational vision science & technology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Eric G RomanowskiDepartment of Ophthalmology, University of Pittsburgh, Pittsburgh, PA, USA.
Emily K YoungDepartment of Ophthalmology, University of Pittsburgh, Pittsburgh, PA, USA.
Sonya M MumperDepartment of Ophthalmology, University of Pittsburgh, Pittsburgh, PA, USA.
Kathleen A YatesDepartment of Ophthalmology, University of Pittsburgh, Pittsburgh, PA, USA.
Rachel A F WozniakDepartment of Ophthalmology, University of Rochester Medical Center, Rochester, NY, USA.
Michael E ZegansDepartment of Surgery, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
Robert M Q ShanksDepartment of Ophthalmology, University of Pittsburgh, Pittsburgh, PA, USA.

Funding

Virus Production and Manipulation of Protein/Gene Expression ModuleP30EY008098 · NEI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Ethan A Rossi · 1989 to 2026
$17.8M
Rise of lasR mutant Pseudomonas aeruginosa keratitisR01EY032517 · NEI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SHANKS, ROBERT M · 2021 to 2024
$1.6M
Extensively drug resistant Pseudomonas aeruginosa keratitis outbreak strain:  virulence mechanisms and mitigationR01EY036686 · NEI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ROBERT M SHANKS · 2024 to 2026
$1.4M
NEI NIH HHS P30 EY008098NEI NIH HHS R01 EY032517NEI NIH HHS R01 EY036686
6 · The paper itself

Abstract

Purpose: Antibiotic combination therapy is commonly used for empiric treatment of microbial keratitis, a potentially blinding infection of the cornea. Pseudomonas aeruginosa (P. aeruginosa) is a major cause of severe keratitis, and the 2023 outbreak linked to artificial tears involved a strain resistant to aminoglycosides and fluoroquinolones, resulting in widespread vision loss. Despite various proposed treatments, no consensus exists for management of keratitis caused by the outbreak strain. The purpose of this study was to evaluate the efficacy of cefiderocol (FDC) combined with polymyxin B (PB) against ocular P. aeruginosa keratitis isolates, including extensively drug-resistant (XDR) strains from the 2023 artificial tear-associated outbreak. Methods: Time-kill assays and epsilometer (E-test) synergy testing were performed on a panel of keratitis isolates. Genetic analysis was conducted on mutants with reduced FDC susceptibility. Results: Time-kill assays demonstrated synergy for two XDR outbreak isolates (P < 0.05), whereas the E-test used across diverse keratitis isolates showed additive to indifferent interactions. Quorum-sensing-deficient, sheen-positive strains showed reduced responsiveness (P < 0.01). Non-antagonistic interactions were observed for Serratia marcescens (S. marcescens) and Staphylococcus aureus (S. aureus) keratitis isolates, with synergy for some S. marcescens strains. Mutants with reduced FDC susceptibility harbored mutations in baeS and fepA, yet remained responsive to the antibiotic combination. Conclusions: FDC combined with PB demonstrates promising activity against drug-resistant Gram-negative keratitis pathogens, including XDR P. aeruginosa. Translational Relevance: These findings support the further development of FDC with PB as a candidate therapy for drug-resistant ocular infections.

Indexed as

Anti-Bacterial AgentsCephalosporinsEye Infections, BacterialKeratitisPolymyxin BPseudomonas aeruginosaPseudomonas InfectionsCefiderocolDrug SynergismDrug Therapy, CombinationHumansMicrobial Sensitivity TestsAnti-Bacterial AgentsCefiderocolCephalosporinsPolymyxin B

Identifiers

PMID41222194
PMCPMC12614257

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.