New and developing diagnostic technologies for urinary tract infections

Abstract

Timely and accurate identification and determination of the antimicrobial susceptibility of uropathogens is central to the management of UTIs. Urine dipsticks are fast and amenable to point-of-care testing, but do not have adequate diagnostic accuracy or provide microbiological diagnosis. Urine culture with antimicrobial susceptibility testing takes 2 3 days and requires a clinical laboratory. The common use of empirical antibiotics has contributed to the rise of multidrug-resistant organisms, reducing treatment options and increasing costs. In addition to improved antimicrobial stewardship and the development of new antimicrobials, novel diagnostics are needed for timely microbial identification and determination of antimicrobial susceptibilities. New diagnostic platforms, including nucleic acid tests and mass spectrometry, have been approved for clinical use and have improved the speed and accuracy of pathogen identification from primary cultures. Optimization for direct urine testing would reduce the time to diagnosis, yet these technologies do not provide comprehensive information on antimicrobial susceptibility. Emerging technologies including biosensors, microfluidics, and other integrated platforms could improve UTI diagnosis via direct pathogen detection from urine samples, rapid antimicrobial susceptibility testing, and point-of-care testing. Successful development and implementation of these technologies has the potential to usher in an era of precision medicine to improve patient care and public health.

Emerging Microtechnologies and Automated Systems for Rapid Bacterial Identification and Antibiotic Susceptibility Testing

“…For instance, Liao et al demonstrated a rapid (approximately 3.5 h) AST assay from clinical urine samples by direct culture of urine samples in the presence of antibiotics, followed by analyzing 16S rRNA levels using an electrochemical sensor. 116–118 Clinical validation using patient urine samples demonstrated that this test was 94% accurate in 368 pathogen-antibiotic tests compared with standard microbiological methods. Together with GeneFluidics, Inc., the same team has been developing a multiplex electrochemical biosensor system for rapid pathogen ID in blood samples (Fig.…”

“…The hybridization of probes and targets can be facilitated by electrokinetic heating and mixing. 116,119 (This figure is modified from reference 116 with permission. )…”

Molecular and Imaging Diagnostic Techniques for Urinary Tract Infections: Modern Approaches

“…Performing the biosensor assay using specific probes for specific pathogen identification. Pathogens identification takes 1 hour and can be performed from urine without target purification or amplification and if pathogens are identified, level of 16s rRNA from sample incubated is quantified on biosensor providing susceptibility data within 3½ hours of urine sample collection [5].…”

“…In culture, appropriate number of bacteria in urine sample is estimated and urine from a person with untreated acute urinary tract infection usually contains 10 5 cfu/ml or more bacteria. Biochemical examination techniques are also available, and these include protein reagent strip test, leucocyte esterase strip test and nitrite reagent test to determine proteinuria, specific polymorphonuclear neutrophils [pus cell] and nitrate-reducing pathogens respectively [4,5].…”

Accelerating bacterial growth detection and antimicrobial susceptibility assessment in integrated picoliter droplet platform

“…Phenotypic methods for evaluating antibiotic resistance, in which bacteria are directly grown in the presence of various antibiotics to determine their sensitivity or resistance, are limited by a lengthy assay procedure. Indeed, current standard phenotypic antimicrobial susceptibility tests (AST) in clinical laboratories (e.g., broth dilution and disk diffusion) require a 16 to 20 h incubation period (Davenport et al, 2017; Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Fourth Informational Supplement , 2014). Although many strains of bacteria grow rapidly and some (e.g., E. coli ) can even replicate in as little as every 20 minutes (Fossum et al, 2007; Parija, 2016; Powell, 1956), conventional AST still requires a lengthy incubation period.…”