Purpose: To test cefiderocol, a siderophore-cephalosporin antibiotic for topical monotherapy treatment of experimental extensively drug resistant (XDR) keratitis.
Design: Preclinical study.
Subjects And Controls: Deidentified keratitis isolates, XDR from eye drop outbreak, rabbits, saline, cefiderocol 50 mg/ml, ciprofloxacin 0.3%, and tobramycin 14 mg/ml.
Methods Intervention Or Testing: Cefiderocol antibacterial activity against keratitis isolates (n=135) was evaluated by minimum inhibitory concentration (MIC) testing. Ocular toxicity/tolerability and antibacterial efficacy were tested with experimental rabbit models. Corneal concentrations and stability were assessed using a bioassay.
Main Outcome Measures: MIC analysis for susceptibility, graded tests for ocular toxicity/tolerability, CFU analysis for bacterial burden, corneal cefiderocol concentrations.
Results: 100% of keratitis isolates were susceptible to cefiderocol (n=135), the MIC was 0.125 μg/ml including the XDR isolate (MIC = 0.125 μg/ml). Topical cefiderocol 50 mg/ml was minimally toxic to the ocular surface and was well tolerated. For the XDR isolate, topical cefiderocol 50 mg/ml, significantly decreased corneal CFU compared to ciprofloxacin 0.3%, tobramycin 14 mg/ml, and saline. In addition, tobramycin 14 mg/ml was more effective than the saline control. Mean cefiderocol corneal concentrations were 191x greater than the MIC of the keratitis isolates. Refrigerated cefiderocol maintained antimicrobial activity over a one-month period.
Conclusions: These results demonstrate that cefiderocol is well tolerated on rabbit corneas and is effective against keratitis isolates and was effective against an XDR isolate in a rabbit keratitis model. Given the recent outbreak of keratitis caused by this XDR , cefiderocol is a promising additional antibiotic that should be further evaluated for topical treatment of keratitis caused by antibiotic resistant .
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10491197 | PMC |
| http://dx.doi.org/10.1101/2023.08.31.555778 | DOI Listing |
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