Urinary tract infections (UTIs) are among the most prevalent community- and hospital-acquired infections(~10M annual medical visits), accounting for considerable morbidity and annual US healthcare spend ofgreater than $6B. While UTI pathogens are well understood, patients are frequently treated empirically.The lack of rapid, point of care molecular diagnostics that can identify UTI pathogens results in poorantimicrobial stewardship and high rates of UTI drug resistance.We propose to begin development of a rapid diagnostic assay and workflow that will concurrently detectall UTI pathogens and their associated resistance genes, suitable for point of care clinical applications.This assay is anticipated to allow for more effective personalized treatment of UTIs, reducing rates ofantimicrobial resistance, and improving patient outcomes.As described in an upcoming Nature Biomedical Engineering paper, the Torus Biosystems's qPCR system,Synestiaâ¢, has demonstrated reproducible 30-plex capability, accurate quantitation and SNP detection,sensitivity down to 10 genomic copies, and turnaround times of less than 30 minutes. The consumable isequipped with an embedded pre-quenched microarray that allows for real-time detection of amplificationproducts without opening the reaction chamber. The sensitivity and dynamic range of the Synestia systemhas been evaluated across a range of input concentrations of DNA (101 to 105 copies) and the thresholdvalue was found to be dependent on the log of the input DNA concentration. The platform has alsosuccessfully demonstrated rapid bacteria identification using a multiplex panel specific for 15 bacteriaspecies.This Phase 1 application proposes to develop a 60-plex UTI panel for comprehensive assessment ofuropathogen DNA within 30 minutes on the Synestia platform. In the subsequent Phase 2, we will develop,optimize, and validate a fully integrated consumable including urine sample prep (lysis and extraction) onthe Synestia platform and validate clinical performance in collaboration with select clinical sites. The teamanticipates that the demonstrated assay will constitute a solid basis for further development of acommercial point of care diagnostic test for urinary tract infections. Project Narrative
Rapid and definitive detection of uropathogens is critical for effective, personalized treatment of urinary
tract infections (UTIs) and the control of infection-associated antimicrobial resistance. We have
developed a rapid molecular diagnostic system suitable for near patient, point-of-care use to diagnose
infections and provide therapeutic selection decision support insights. This Phase I SBIR application
outlines the design, optimization and validation of a rapid multiplex qPCR assay for the concurrent
detection of 32 uropathogens and 18 drug resistance genes associated with UTIs. Accounting ; Affect ; Antibiotics ; Antibiotic Agents ; Antibiotic Drugs ; Miscellaneous Antibiotic ; Bacteria ; Biological Assay ; Assay ; Bioassay ; Biologic Assays ; Biomedical Engineering ; bio-engineered ; bio-engineers ; bioengineering ; Cells ; Cell Body ; Chemistry ; Diagnosis ; DNA ; Deoxyribonucleic Acid ; Drug resistance ; drug resistant ; resistance to Drug ; resistant to Drug ; Fractionation ; Chemical Fractionation ; FRACN ; Fractionation Radiotherapy ; Future ; Genes ; Gold ; Community Hospitals ; Infection ; Laboratories ; Morbidity - disease rate ; Morbidity ; Mutation ; Genetic Alteration ; Genetic Change ; Genetic defect ; genome mutation ; Nucleic Acids ; Nucleotides ; Paper ; Patients ; Recurrence ; Recurrent ; Sensitivity and Specificity ; Technology ; Testing ; Time ; Urinary tract infection ; Urinary tract infectious disease ; urinary infection ; Urine ; Urine Urinary System ; Work ; Health Care Costs ; Health Costs ; Healthcare Costs ; Infection Control ; Antibiotic Resistance ; Resistance to antibiotics ; Resistant to antibiotics ; antibiotic drug resistance ; antibiotic resistant ; Diagnostic tests ; Healthcare ; health care ; TimeLine ; base ; improved ; Nucleic Acid Amplification Tests ; Nucleic Acid Testing ; Solid ; Clinical ; Phase ; Medical ; Nosocomial Infections ; Hospital Infections ; Hospital acquired infection ; institutional infection ; insight ; Recovery ; Convection ; Collaborations ; Therapeutic ; Antibiotic Treatment ; bacterial disease treatment ; bacterial infectious disease treatment ; Antibiotic Therapy ; Diagnostic ; Nature ; Research Specimen ; Specimen ; Complex ; Reaction ; System ; Visit ; infectious disease diagnosis ; communicable disease diagnosis ; Performance ; synthetic DNA ; synthetic construct ; Sampling ; Genomics ; Molecular Diagnostic Methods ; Molecular Diagnostic Technics ; Molecular Diagnostic Techniques ; Lysis ; Cytolysis ; Antimicrobial resistant ; Resistance to antimicrobial ; anti-microbial resistance ; anti-microbial resistant ; resistance to anti-microbial ; resistant to anti-microbial ; resistant to antimicrobial ; Antimicrobial Resistance ; Detection ; Reproducibility ; Clinical Sensitivity ; Patient-Focused Outcomes ; Patient outcome ; Patient-Centered Outcomes ; Small Business Innovation Research Grant ; SBIR ; Small Business Innovation Research ; Validation ; Preparation ; Development ; developmental ; point of care ; design ; designing ; Uropathogen ; clinical research site ; clinical site ; pathogen ; pathogenic bacteria ; bacteria pathogen ; bacterial pathogen ; Population ; Prevalence ; antimicrobial ; anti-microbial ; Pathogen detection ; clinical application ; clinical applicability ; prototype ; point-of-care diagnostics ; multi-drug resistant pathogen ; MDR organism ; MDR pathogen ; multi-drug resistant organism ; multidrug resistant organism ; multidrug resistant pathogen ; multiple drug resistant organism ; multiple drug resistant pathogen ; resistance gene ; resistance locus ; resistant gene ; personalized medicine ; personalization of treatment ; personalized therapy ; personalized treatment ; amplification detection ; diagnostic panel ; diagnostic assay ; molecular diagnostics ; pathogenic fungus ; fungal pathogen ; fungi pathogen ; Rapid diagnostics ; rapid test ; rapid assay ; rapid tests ; diagnostic platform ; diagnostic system ; detection sensitivity ;
