Cefiderocol Is an Effective Topical Monotherapy for Experimental Extensively Drug-Resistant Pseudomonas aeruginosa Keratitis

Romanowski, Eric G.; Mumper, Sonya M.; Shanks, Hazel Q.; Yates, Kathleen A.; Mandell, Jonathan B.; Zegans, Michael E.; Shanks, Robert M.Q.

doi:10.1016/j.xops.2023.100452

Cited by 3 publications

(2 citation statements)

References 44 publications

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“…It carries genes for Verona integron-mediated metallo-β-lactamase and the Guiana extended-spectrum β-lactamase which has not been formerly seen in the United States. This bacterium is highly resistant to standard of care antibiotics for P. aeruginosa keratitis (ciprofloxacin and tobramycin) with minimum inhibitory concentrations above 32 µg/mL ( 1 , 3 ). Here, we report the genome of an isolate from this outbreak using whole genome sequencing (WGS) made using Illumina and Nanopore and assembled with Unicycler software.…”

Section: Announcementmentioning

confidence: 99%

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Genome sequence generated by hybrid Nanopore-Illumina assembly of an extensively drug-resistant Pseudomonas aeruginosa strain from a keratitis outbreak

Calvario,

Shanks

2024

Microbiol Resour Announc

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Section: Announcementmentioning

confidence: 99%

“…MIC data are reported on the CDC’s website that describes antibiotic susceptibility for this isolate. Here, we investigate isolate “AR-1270,” [also noted as CDC1270 ( 1 , 3 )]. The CDC assigned BioSample ID SAMN33435243 to this isolate.…”

Section: Announcementmentioning

confidence: 99%

Genome sequence generated by hybrid Nanopore-Illumina assembly of an extensively drug-resistant Pseudomonas aeruginosa strain from a keratitis outbreak

Calvario,

Shanks

2024

Microbiol Resour Announc

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The Efficacy of Topical Cefiderocol Treatment of Experimental Extensively Drug-Resistant Pseudomonas aeruginosa Keratitis Is Dependent upon the State of the Corneal Epithelium

Romanowski,

Mandell,

Jhanji

et al. 2024

Antibiotics

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Background: An overlooked factor in the efficacy of topical antibiotics to treat bacterial keratitis is the state of the corneal epithelium. Recently, we evaluated topical cefiderocol for the treatment of extensively drug-resistant (XDR) Pseudomonas aeruginosa (PA) keratitis in eyes with the corneal epithelium abraded. The goal of this study was to use the same model with the corneal epithelium left intact to evaluate the efficacy of cefiderocol and other antibiotics and compare the results to those of the previous study. Methods: NZW rabbit corneas with intact epithelium were inoculated with XDRPA. After 16 h, the rabbits were topically treated with cefiderocol 50 mg/mL, ciprofloxacin 0.3%, tobramycin 14 mg/mL, or saline. Following 8 h of treatment, the corneas were harvested for CFU determinations and cefiderocol concentrations. Results: Only cefiderocol significantly decreased CFU of the XDRPA strain compared with saline. The CFU in the cefiderocol and tobramycin-treated corneas for the XDRPA strain with initially intact epithelium were 1.83–1.4 Log10 greater than those produced in corneas with the abraded epithelium (p < 0.05). Cefiderocol concentrations were 5.02× less in corneas with initially intact epithelium. Conclusions: The efficacy of cefiderocol and tobramycin to treat experimental XDRPA keratitis is dependent on the state of the corneal epithelium.

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Efficacy of Cefiderocol Against Endophthalmitis Isolates

Schilling,

Hii,

Shanks

et al. 2024

Antibiotics

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Background/Objectives: Endophthalmitis is an intraocular microbial infection that can lead to permanent blindness, even with prompt anti-microbial therapy. Multi-drug-resistant organisms are on the rise, potentially limiting the efficacy of current empiric antibiotic therapies of intravitreal ceftazidime and vancomycin. Cefiderocol is a recent FDA- and EMA-approved antibiotic for multi-drug-resistant Gram-negative bacteria. Methods: To better understand its potential utility in the treatment of ocular infections, the MIC of cefiderocol was compared to ceftazidime and amikacin in endophthalmitis bacterial isolates using Epsilometer testing. Because vancomycin is commonly given concomitantly as part of empiric endophthalmitis treatment, possible synergistic and antagonistic effects of concomitant vancomycin and cefiderocol were also evaluated. Results: Cefiderocol was found to have lower MIC values compared to ceftazidime for Pseudomonadales or Enterobacterales species. When comparing the MICs of cefiderocol and vancomycin, there appeared to be no antagonism between the two antibiotics. Conclusions: This is the first report exploring the use of cefiderocol in endophthalmitis strains. The results of this study show this is a promising antibiotic for multi-drug-resistant Gram-negative organisms but further research is needed to investigate its intraocular safety profile.

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Cefiderocol Is an Effective Topical Monotherapy for Experimental Extensively Drug-Resistant Pseudomonas aeruginosa Keratitis

Cited by 3 publications

References 44 publications

Genome sequence generated by hybrid Nanopore-Illumina assembly of an extensively drug-resistant Pseudomonas aeruginosa strain from a keratitis outbreak

Genome sequence generated by hybrid Nanopore-Illumina assembly of an extensively drug-resistant Pseudomonas aeruginosa strain from a keratitis outbreak

The Efficacy of Topical Cefiderocol Treatment of Experimental Extensively Drug-Resistant Pseudomonas aeruginosa Keratitis Is Dependent upon the State of the Corneal Epithelium

Efficacy of Cefiderocol Against Endophthalmitis Isolates

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