A Rapid Antimicrobial Susceptibility Testing based on Brownian Motion for Urinary Tract Infection

Abstract

According to the 2013 survey of top ten leading causes of death reported by the Ministry of Health and Welfare sepsis has become the 10th cause of women’s death in Taiwan In the U S sepsis also ranks in the top ten leading causes of death Except for the identification of pathogen (IP) the key for a successful treatment of sepsis is the antimicrobial susceptibility test (AST) Clinically doctors are used to performing an empirical therapy before the AST comes clear However the blind uses of antibiotics usually enhance the drug resistance and even worse may counteract the effects of future antibiotic therapies Lately automated platforms designed for the AST and IP are commonly used in research hospitals The outcomes are highly comparable to conventional methods However the turnaround times for the AST and IP require 3-4 hours and 8-24 hours respectively which remain insufficient to improve the patient mortality (>50%) The next generation sequence (NGS) technique requires plenty of time (>24 hours) to complete the whole genome sequencing of pathogen and continuously alignment of antibiotic resistance gene sequence The high cost and large time consumption therefore impede the NGS prevalence in clinical uses until now Multiplex PCR although claimed to get outcomes in 2-3 hours without time-consuming culture is intrinsically incapable of dealing with Gram negative bacteria and unknown antibiotic resistance genes (unknown mechanism) To achieve rapid simple and quantitative diagnostics for the AST we develop a unique technique based on Brownian motion of functionalized particles combining with immunoassays As bacteria bind to the particles Brownian motion will decline due to the increase of equivalent particle diameter Herein the assessment of the AST depends on a direct relationship between the concentration of pathogens and drug dosage When pathogens are susceptible to some drugs the growth of bacteria will be halted or reverse resulting in none or increased Brownian motion over time; otherwise the Brownian motion will decrease over time In addition with several types of antibody-conjugated fluorescent particles co-suspended in a medium several bacteria can be monitored simultaneously Upon the success of this method the goals to rapid (

Date of Award	2018 May 21
Original language	English
Supervisor	Tainsong Chen (Supervisor)