Scanning electron photomicrograph of dual species biofilm with C. auris and PA01 on uncoated endotracheal tube (C) and CeraShield Coated Endotracheal Tube (D) after 48 hours. Image courtesy of N8 Medical
The Centers for Disease Control and Prevention (CDC) has recently identified medical devices used in the ICU as a major source of antibiotic-resistant infections. N8 Medical’s CeraShield technology may help reduce such infections by preventing fouling and formation of bacterial and fungal biofilms on device surfaces. FDA has designated the company’s CeraShield Endotracheal Tube (ETT) as a “breakthrough” device, pursuant to the 21st Century Cures Act based on its potential life-saving properties. And N8 reported that Frost & Sullivan had selected it as the winner of a North American New Product Innovation Award.
The first in-human studies in mechanically ventilated ICU patients show that the device is able to prevent ESKAPE pathogens in endotracheal tube aspirates and on the device itself. In vitro data show that the device is also able to prevent colonization by Candida auris, which CDC has recently elevated to “urgent” concern. The technology is broadly applicable to any indwelling medical device across multiple medical specialties.
Indwelling medical devices, such as the endotracheal tubes used in mechanical ventilators, are abiotic, meaning that they are very good breeding grounds for bacteria and fungi, said Carl Genberg, N8 Medical's Chief Scientific Officer. “If you have an abiotic surface, bacteria will rapidly grow,” he continued. “If you take an endotracheal tube out of its sterile packaging and intubate a patient, within minutes you will start to have bacteria growing on it, and within hours you probably will have formed biofilm.”
He said that biofilms secrete exopolysaccharide, which is very difficult for conventional antibiotics to eradicate. “Conventional antibiotics need a target, such as rapidly dividing cells, which is a characteristic of DNA synthesis,” Genberg said. “But when you have a biofilm, most of the biofilm is asleep. Only the outer ring of the biofilm has any degree of DNA activity,” he noted.
Genberg explained that, even worse, a third of the cases of colonization on endotracheal tubes are polymicrobial. “You have staph and candida, [for example], and they are living in the same apartment on the endotracheal tube and they are able to exchange resistant genes, so that a strain that was previously not resistant to an antibiotic can get the benefit of a resistant strain from another bacterium that is,” he said. “And that's why polymicrobial biofilms pose such a threat.”
But ceragenins (CSAs) could help to prevent pathogens from colonizing in the first place. CSAs are synthetic, nonpeptide, small-molecule mimetics of endogenous host defense or antimicrobial peptides. They have broad-spectrum activity that mimics these peptides, including antimicrobial, anti-inflammatory, and anti-adhesive properties.
N8’s CSA formulation, CSA 131, licensed from Dr. Paul B. Savage, a professor of chemistry and biochemistry at Brigham Young University, initially prevents biofilm from adhering to a device. Then, once the antiadhesion effect breaks down, the last line of defense is the activity of the compound on the surface of the device, which would pierce the membrane of bacteria, leading to rapid ion efflux.
“CSAs are broad-spectrum compounds, typically cationic, and nature has so divided the world that bacterial membranes are typically anionic,” said Genberg. “So this is an electrostatic attraction between a positively charged compound and a negatively charged compound, and this rips apart the bacterial membrane, so that you have rapid ion efflux.” There are now more than 90 peer-reviewed journal articles on the ceragenin technology.
N8 works with its partner, Hydromer, who produces lubricious coatings that are widely used in urinary catheters, in developing a material that can be dip coated on a variety of medical devices. “We’re using one of those [coatings] and we are mixing in our compound CSA 131,” said Genberg.
Genberg said that he expects that the endotracheal tube will be approved for use in Canada in 2020, and the company is currently working with FDA for approval in the United States. Genberg added that N8 Medical is currently seeking strategic partnerships in various fields of use.