Near patient molecular diagnostics test for infections

ABSTRACT Currently there are no FDA cleared molecular based tests for urinary tract infection UTI pathogen identification and antimicrobial susceptibility testing to replace the andapos gold standardandapos of dipstick urinalysis and urine culturing All pathogen identification tests still rely on clinical isolates from urine cultures largely unchanged from Kochandapos s postulates developed in the th century as general guidelines to identify pathogens What has changed over time however is the dramatic and progressive emergence of antibiotic resistance among these pathogens Data from the Centers for Disease Control and Prevention CDC National Healthcare Safety Network NHSN indicate that of the pathogens isolated from hospital acquired infections HAIs now are resistant to at least major classes of antibiotics Recent developments in molecular diagnostic testing for multidrug resistant MDR pathogens can provide a sensitive specific and real time solution to support active surveillance driven infection control interventions but these PCR based tests can only be performed on simple specimen matrices such as swabs or positive blood culture media blood to broth ratio No molecular based method is cleared by the FDA to test directly on urine or whole blood samples The goal of this Commercialization Readiness Pilot CRP Grant is to accelerate the commercialization effort of the program outcome from our NIAID SBIR R AI project titled An Integrated Diagnostic System for Rapid Antimicrobial Susceptibility Testing AST We propose technical assistance on regulatory strategy development and cost effective manufacturing as well as later stage research and development activities on independent replication of key studies in compliance with FDA requirements and ISO standards The goal of our NIAID Advanced Technology SBIR project is to develop and validate RAST rapid antimicrobial susceptibility testing an integrated and compact diagnostic system that enables clinicians direct point of care POC with an evidence based selection of antibiotics for treatment of acute bacterial infections Our first compact automated system is capable of rapid pathogen identification ID and AST directly from patientandapos s samples with evidenced based information to start patient specific antimicrobial treatment It is expected to obtain a CE Mark after the coming ISO surveillance certification audit in February However the FDA clearance is hindered by no molecular based predicate test cleared by the FDA for urinary tract infections UTI the low cost of conventional dipstick urinalysis tests and the lack of fresh urine specimens through a multi site clinical feasibility study We will overcome these hurdles through the following aims TECHNICAL ASSISTANCE Aim Obtain a risk based classification of the Class II device through a de novo request with external regulatory assistance from NSF International an international certification organization in months Aim Reduce the cost of goods sold of andlt $ for cartridge and andlt $ k for system with external manufacturing development assistance LATE STAGE RESEARCH AND DEVELOPMENT ACTIVITIES Aim Conduct a multi center clinical performance study and demonstrate andgt clinical sensitivity specificity and andgt susceptibility categorical agreement In this study we focus on validating the rapid UTI diagnostic device according to federal regulations CFR microorganism differentiation and identification device CFR antimicrobial susceptibility test powder and CFR fully automated short term incubation cycle antimicrobial susceptibility testing system The FDA product codes for such systems are JSS and LON The regulatory strategy will be finalized in Aim Regulatory for preparation of the clinical protocol and multicenter clinical performance study in Aim Clinical study that will utilize the cost effective system and consumables optimized in Aim Manufacturing Narrative The main goal of this CRP research project is to accelerate the commercialize of the SBIR program outcome that integrates lab automation rapid molecular analysis genotypic pathogen quantification and phenotypic antibiotic conditions to dramatically improve the sensitivity and specificity of rapid evidence based pathogen identification ID and antimicrobial susceptibility testing AST directly from patient fresh urine samples