SBIR/STTR Award attributes
PROJECT SUMMARY Infective EndocarditisIEis a life threatening disease that affects roughlyAmericans annuallyIE is characterized by microbial vegetations on the endocardial surface which induce serious heart damage and persistent bloodstream infectionsBSIsleading to sepsisLeft untreated IE is fatalAmong the criteria to establish IE and treat patients most effectivelyblood cultures are indispensable to identify the etiologic agentCultureshoweverdisplay two major weaknesses which delay the administration of the proper antimicrobialsHigh turnaround time of days or even weeks andhigh prevalence of false negative results due to either pre treatment with antibiotics or the presence of difficult to culture pathogensAs time is of essence for optimal outcomes with minimal complicationstreatment is often initiated prior to diagnosis with a cocktail of broad spectrumi enot targetedantimicrobialsleaving the majority of patients treated inappropriately and those without the disease treated unnecessarilyIt is therefore critical to advance innovative diagnostic approacheswhich do not rely on culturingin order to rapidly transition to personalized antimicrobial interventionsTo address this unmet needHelixBind will develop the first culture free diagnostic assay capable of identifying pathogens which induce IE in underhoursHelixBind s approach leverages multiple novel innovations from sample to answerFurtheras detection does not require culturesour approach is particularly suited to the detection of fastidious pathogenswhich today s diagnostic standard frequently fail to detectOur proposed Infective Endocarditis Pathogen Identification assaytermed IE PIDis expected to have a profound clinical impact by enabling the physician to apply a personalized and evidence driven intervention within a few hoursrather than daysultimately improving both outcomes and antimicrobial stewardshipPreviouslyHelixBind demonstrated a Core Pathogen IdentificationC PIDplatformaimed at thegeneralpatient population at risk for sepsis caused by bloodstream infectionsBSIsC PID detectsof the most prevalent BSI causing pathogens in a single test directly from bloodrequires less thanhours from sample to answerand displayed single CFU ml LODs across the entire panelC PID was validated in a blinded pilot study utilizing clinical specimens and demonstrated andgtsensitivity and andgtspecificityIE PID will utilize similar processes as C PID and will detect the most prevalent pathogens associated with IE including fastidious and uncultureable pathogensOur Specific Aims with quantifiable deliverables are designed to demonstrate feasibility within the time and capital constraints of a Phase ITo succeedwe have assembled a team of experts in assay development and artificial nucleic acidssupported by leading clinical microbiologists for guidanceHaving achieved our Specific Aimswe willin Phase IIdevelop deployable instrumentation consumablesexpand the test panel to include pathogens generally deemed asunculturablesuch as Coxiella burnetii and Bartonella sppand verify and validate an automated diagnostic platform with clinical specimens in a blinded study PROJECT NARRATIVE Infective EndocarditisIEis a serious and life threatening disease and a significant economic burden due to prolonged intensive treatmentEarly microbiological diagnosis is crucial to improving outcomesbut current standards employing blood cultures are lethargic and often yield false negative resultsThis delay in crucial information prevents the administration of the evidence based antimicrobial treatment precisely when it is maximally beneficialHelixBind will address this problem and develop a novel turn key approach for early microbiological IE diagnosisIn this Phase I SBIRwe propose to lay the groundwork for the development of the first fully automated diagnostic capable of identifying the most prevalent pathogens causing IEincluding those difficult or impossible to detect by standard methodsdirectly from phlebotomy specimenswithout prior enrichmentreducing the diagnosis time from days or even weeks to just hoursThe information provided would enable the clinician to apply an evidence driven intervention from the onset of disease symptoms
