Antimicrobial Intravascular Catheter Lock Solutions Based on Endogenous Nitric Oxide Release Agent

! AbstractIntravascularIVcatheters in the hospital setting are associated with a high rate of bacterial colonizationresulting in andgtdeaths annually in the U Sfrom catheter related blood stream infectionsCR BSIsNewer commercial catheters pre loaded with silver or antibiotics within their walls have failed to dramatically reduce this very significant problemA variety of catheter lock solutionscatheters that are filled with these solutions when not in usecontaining antibioticsethanol and other antimicrobials are currently employed in hospitals around the worldHowever none of the antimicrobial agents used in existing lock solutions are able to diffuse through the walls of the catheters and prevent infection and biofilm formation on the outer surfaces of the cathetersFurthermicrobial biofilm commonly formed on catheter surfaces is particularly resistant to antibiotic treatment owing to the inability of the antibiotics to penetrate the protective polysaccharide matrix associated with biofilmNitric oxideNOis an endogenous antimicrobial agent that kills planktonic bacteria as well as those microbes within a biofilmRecent research has demonstrated that NO release from catheters surfaces using NO donors incorporated into the walls of the catheters is quite effective in preventing bacterial colonizationHoweverthe use of exogenous NO donors within the walls of catheters will likely face significant FDA hurdles associated with ensuring the safety of the specific NO donors utilizedTo move NO release catheters more quickly into clinical useNOTA plans to create a simple NO release IV catheter lock solution that will be reconstituted from a dry powder statein vialby hospital personnel immediately before useand then loaded into the IV catheter using a syringeThe solution will contain a proprietary mixture of S nitrosogutathioneGSNOa known carrier of NO within the human bodyalong with S glutathione and or ascorbatevitamin Cas accelerants to control the rate of NO release from GSNO over many hoursin physiological saline solutionPhase I will focus onoptimizing the GSNO additive formulation s NO release kinetics and examining dry state storage stability overmonths of different recipesdetermining the duration and magnitude of NO release for different concentrations of lock solution reagents when loaded within the lumen of catheters made of different polymeric materialsandassess the antimicrobial activity of different catheter tubing loaded with fresh GSNO additive lock solutionsreplaced dailyoverd periods against Saureus and Paeruginosa using a CDC bioreactor modelGiven the known presence of GSNO in bloodthe proposed use of antimicrobial GSNO based catheter lock solutions should be a very safeeffectiveand inexpensive new approach to greatly reduce the rates of CR BSIs NARRATIVE IntravascularIVcatheter associated bloodstream infections are a very major problem in the hospital settingcausing andgtdeaths annually in the U Saloneand also significantly increasing healthcare costsEfforts to develop silver and antibiotic impregnated catheters haveto datenot resolved the high infection rates associated with IV cathetersNOTA Laboratories now plans to develop a new product line of various dry reagent formulations containing S nitrosoglutathioneGSNOalong with appropriate additives in a saline backgroundthat can be reconstituted with pure water at the patient s bedside for use as completely new and much more effective antimicrobial lock solutions in the hospital settingThe NO gas generated within the lock solution from the GSNO confined within the lumen sof catheters will be capable of preventing bacterial colonization on both the inner and outer surfaces of the catheter owing to NO s ability to readily permeate the walls of the catheternot possible with antibioticsand serve as localized bactericidal agent and also prevent disperse microbial biofilm