Ceragenins mimic organic antimicrobial agents

Key Points

Singapore-A proprietary class of compounds called ceragenins could be used in contact lens disinfectant solutions to prevent the growth of biofilms in contact lens storage cases and to provide an anti-infective surface on IOLs and disposable contact lenses, said Paul B. Savage, PhD. He presented in vitro data on the use of ceragenins for ophthalmic applications here at the Asia-ARVO meeting.

In preliminary tests at various labs, the compounds have been highly effective against several strains of bacteria and fungi, he said. Ceragenix Pharmaceuticals Inc., headquartered in Denver, is developing and commercializing anti-infective drugs based on this class of compounds.

Powerful agent

The ceragenin compounds that Dr. Savage developed in his lab follow the same approach as evolving antimicrobial peptides: controlling bacterial growth by actively attacking bacterial membranes.

"That means they are broad-spectrum, very fast acting, and unlikely to engender resistance," Dr. Savage said.

In preliminary lab tests, the molecules have shown good activity even against ocular pathogens that are resistant to other antibacterial agents, he said.

During in vitro testing, a developmental ceragenin-based contact lens disinfectant solution was virtually able to eradicate five strains of bacteria and fungi within 1.5 hours. The testing was performed following specifications of the FDA guidance document for approval of contact lens disinfectant solutions.

Tests also have been conducted against the fungal pathogen Fusarium solani, the organism responsible for a 2006 worldwide outbreak of eye infections that resulted in the voluntary recall of a multipurpose contact lens solution (ReNu with MoistureLoc, Bausch & Lomb). In these tests, the ceragenin-based contact lens disinfectant solution was compared with two leading brands on the market in its ability go kill Fusarium solani.

The ceragenin solution showed a 4.19 log reduction at 1.5 hours of soaking versus 0.48 and 0.26 log reductions for the two leading brands. A 4.0 log reduction is equal to a 99.99% kill, and the limit of detection in this test was 4.19 log, which the ceragenin solution achieved. At 6 hours, the two comparators had achieved log reductions of 3.07 and 0.83.

"These [ceragenins] are very active against Fusarium," Dr. Savage said.

In addition to addressing whether the antimicrobials would kill bacteria, the tests also evaluated how fast they would do so, he added.

"They're very rapid, so we're able to remove a fairly large inoculum of bacteria completely within a short time, most of them within an hour and a half," Dr. Savage said. "That's important for sterilizing contact lenses."

Eliminating biofilms

Another potential use of ceragenins is eradication of biofilms, slime-like aggregations of bacteria or fungi that can develop nearly anywhere bacteria grow and are very difficult to eradicate.

Biofilms are not completely static and continually release bacteria into the surrounding field, leading to a weak but persistent bacterial exposure. Because of those characteristics, many antibiotics or antimicrobials lose efficacy against biofilms.

In ophthalmology, biofilms could be a problem if they formed on contact lenses kept in storage cases, Dr. Savage said. It has been shown that biofilms can form in those cases and could end up on the lenses, he added.

The ceragenin solution has been tested against a strain of fungal biofilm (Candida) and was virtually able to eradicate the biofilm within 6 hours (a 6.0 log reduction). Two of the three leading commercial brands evaluated in the same test achieved log reductions of less than 1.0; the third achieved a log reduction of less than 2.0.

In addition to conducting in vitro testing, Dr. Savage has begun to test the compounds in a rabbit model. Other centers are testing non-ophthalmic applications of ceragenins.