Potential Solution for Drug Resistant Keratitis

Scientist using a microscope

The Charles T. Campbell Ophthalmic Microbiology Laboratory — in collaboration with Dartmouth-Hitchcock Medical Center – has submitted for publication a highly clinically relevant preclinical study for the recent extensively drug resistant (XDR) Pseudomonas aeruginosa keratitis outbreak. A preprint of the submitted manuscript is available at bioRxiv and is in the process of peer review.

The outbreak of Pseudomonas aeruginosa keratitis linked to EzriCare Artificial Tears eye drops bought on Amazon was all over the news this summer. While this would normally be of concern, what makes matters worse is that the particular strain is extensively drug resistant, explained Robert M. Q. Shanks, PhD, Associate Professor, Department of Ophthalmology, Basic Science Director, Campbell Lab. “Crucially, it is resistant to ALL antibiotics used in ophthalmology for treatment of infections,” he added. This outbreak has led to many patients losing their vision, eyes, and in some cases, their lives.

The Campbell Lab read the Centers for Disease Control and Prevention information on this strain and found it was susceptible to an intelligently designed antibiotic called cefiderocol, which is used for treating urinary tract infections and pneumonia and had never been tested for use in the eye.

The lab found that 100 percent of Pseudomonas aeruginosa keratitis isolates from the University of Pittsburgh Campbell Laboratory strain collection were susceptible to cefiderocol, suggesting that it would work for the eye. “This is a unique source that we have, collected by former director Regis P. Kowalski, that really helps our Department stand out,” Dr. Shanks said.

With that in mind, the lab obtained the outbreak strain from the CDC and used it in its animal keratitis model. “This was the first use of topical cefiderocol in the eye to treat a corneal infection,” said Eric G. Romanowski, MS, Research Instructor of Ophthalmology and Research Director of the Campbell Lab.

Cefiderocol was able to effectively treat the animals, whereas the standard of care antibiotics that ophthalmologists normally use were unable to control the infection. Additionally, cefiderocol was well tolerated by the animals when they were treated with eye drops of the drug. A topical formulation of five percent cefiderocol was used and found to be non-toxic.

“Together, this gives a potential solution for ophthalmologists to treat extensively drug resistant Pseudomonas aeruginosa keratitis and potentially save vision,” Dr. Shanks said. “This has inspired our collaborator Michael Zegans, MD, at Dartmouth to develop a clinical trial with human patients.”