MicroUDxTM: a Rapid Diagnostic Tool That Will Prevent Death and Disability From Common Infections
MicroUDxTM: a Rapid Diagnostic Tool That Will Prevent Death and Disability From Common Infections
Background & Rational:

 Antibiotics are a major underpinning of modern medicine. The global rise of antimicrobial
 resistant (AMR) organisms is a serious world health problem. With few new antimicrobial drugs
 on the horizon, it is imperative that we develop novel approaches to extend the service life
 of our existing drugs. AMR is a complex problem that is being driven by a wide range of
 factors. More than half of the antibiotics prescribed have no medical benefit, and outpatient
 visits for uncomplicated urinary tract infections (UTIs) are a major contributor to this
 problem. Recent studies have shown that nearly half of people treated for UTIs receive the
 wrong frontline drug and in 75% of patients, the duration of therapy is inappropriate.
 Limitations in the current diagnostic technology make it impossible to identify UTI pathogens
 and measure their antibiotic sensitivities during the short out-patient clinical visits that
 are typical for most UTI patients. These circumstances result in the inappropriate use of
 stronger than necessary or inappropriate antimicrobials. The aim of this study is to develop
 and evaluate a system that can detect bacteria in urine and find the best antibiotic in under
 4 hours, thus enabling a rapid diagnosis and use of the most appropriate and cost-effective
 antimicrobial agent for the agent detected.
Testing done in this study will be performed either on bacterial isolates stored in the
 microbiology laboratory at the Diagnostic and Scientific Center in Calgary, or on up to one
 milliliter of residual urine sample submitted to the diagnostic laboratory with a request for
 urine culture and sensitivity. All urine cultures will be performed and reported in
 accordance with standards laboratory protocols. Research testing will only be done on
 residual sample once patient samples are processed or reported on for clinical purposes.

 During the first phase of the study, metabolic biomarkers for uropathogens will be identified
 using mass spectrometry on sub-cultures of frozen isolates from the diagnostic microbiology
 laboratory. This will include at least 50 isolates each of uropathogens consisting of but not
 limited to Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Enterobacter species,
 Proteus mirabilis, Citrobacter species, Staphylococcus aureus, Staphylococcus saprophyticus,
 Pseudomonas aeruginosa, Enterococcus species, and Candida species. Biomarkers that are
 present in greater than 95% of the isolates will subsequently be using the analysis of 2000
 negative, and 2000 positive urine cultures. Compounds that are subsequently identified as
 high yield will be selected for carbon 13 labeling to service standards.

 In phase II of the study, following the development of a biomarker enrichment device at the
 CMRF, a performance urinalysis of the device will be conducted using residual urine sample
 from 1000 negative and 2000 positive urine specimens as outlined above. The performance of
 the new device will be evaluated relative to standard cultures and urine liquid
 chromatography-mass spectrometry.

 Following the creation of a sensitive and specific assay, a prospective study will be carried
 out at the diagnostic microbiology laboratory. 3000 sample submitted for urine culture will
 be process in parallel with the new device and standard microbiology procedures. Sensitivity,
 specificity and predictive value for each analyte compared to standard culture will be
 determined in this portion of the study. Cost calculations and performance characteristics
 including turnaround time of the new assay will be compared to that in the standard
 laboratory procedure.
Inclusion Criteria:

 -  Patients who have not submitted urine samples will not be included as the samples are
 required for both standard testing and research. This would include patients who are
 being treated empirically by physicians.

 Exclusion Criteria:

 -  Patient's who have not submitted urine samples for culture will not be included in
 study.