Rapid UTI Diagnostics in Lower Urinary Tract Dysfunction Among Catheter Users

Overview

Patients who seek care through MedStar National Rehab Hospital's clinic believing they have a UTI will be enrolled in this trial. They will be pre-screened after consent according to a standard-of-care clinical symptom measure called the USQNB. If determined by this measure to be at high or moderate likelihood of having a UTI, they will be assigned to the presumed UTI arm and instructed to come to the clinic to provide a urine sample and undergo standard diagnostic testing to determine if a UTI is present. Those not assigned to the presumed UTI arm at this phase are assigned to the presumed no UTI arm and do not present to the clinic. These tests include a repeated questionnaire about the UTI symptoms they are experiencing and collection of a urine sample from a freshly changed indwelling catheter for standard clinical urinalysis testing and culture. Based upon the clinical guideline-informed results of these standard clinical tests, patients will be assigned into one of two potential arms (suspected UTI or suspected non-UTI) based on whether or not they are diagnosed with UTI at that visit. Arm 1 (presumed UTI) participants will have a second urine sample collected at the time of the visit from the used indwelling catheter bag in addition to the freshly changed catheter sample, and both will be divided into three portions: one for repeat clinical tests and culture, one for assessment using the experimental Jiddu device, and one to be stored for potential future studies. The study doctor will then determine antibiotic choice according to standard clinical decision making and record, but not prescribe, that choice. Once results are obtained from the samples sent for experimental analysis, the study doctor will use those results in addition to their best clinical judgement and all standard available clinical evidence to choose the antibiotic treatment. Arm 1 participants will then complete urine symptom surveys at day 3 and 7 during antibiotic use to determine effectiveness of antibiotics prescribed. In the event of standard urine culture results differing from the Jiddu-produced pooled AST values rescue antibiotic consisting of the antibiotic choice based on best clinical judgement using this newly available evidence will be used to ensure safety and this survey clock will restart and include a USQNB on day 10. Arm 2 participants will repeat the urinary symptoms questionnaire 3 and 7 days after their initial completion to see if their symptoms have changed and would allow them to qualify. If they remain unqualified at 7 days, they will be instructed to fill out another survey the next time they think they have a UTI. This process will repeat until they either qualify to become an Arm 1 participant or 6 months have passed since they first consented.

Participants will receive USQNB symptom surveys weekly for 6 weeks, and will have the survey made available to them as many times as they develop urinary symptoms over the course of the 6 month study. When a participant develops symptoms suggestive of UTI, they will complete the USQNB provided. If they are considered to have a moderate or high likelihood of UTI, they will be assigned to the presumed UTI arm and present to the MNRH clinic for evaluation and treatment of their presumed UTI. At the clinic, the study physician will assess their symptoms and obtain a urine sample from a fresh catheter for dipstick testing. Based on the symptom assessment and dipstick results (performed when confirmed high or moderate profile per USQNB), participants will be classified as either a screen pass (presumed UTI) or a screen fail (no presumed UTI). Screen pass and screen fail definitions for UTI are based on the following: Screen pass: 1. Confirmed High or moderate profile per USQNB within the past 24 hours; and 2. Dipstick-determined Nitrite (N) \& Leukocyte Esterase (LE) are "strong positive" (both N positive and LE moderate or large), "inflammation positive" (N=negative and LE=moderate or large), or "indeterminate" (either LE=small with N positive or negative; or LE=negative or trace and N positive). Screen fail: 1. Confirmed High or moderate profile per USQNB within the past 24 hours; and 2. Dipstick-determined Nitrite (N) \& Leukocyte Esterase (LE) are "strong positive" (both N positive and LE moderate or large), "inflammation positive" (N=negative and LE=moderate or large), or "indeterminate" (either LE=small with N positive or negative; or LE=negative or trace and N positive). The definition of "screen pass" for presumed UTI diagnosis and screen fail are based in the 2010 IDSA Guidelines, the evidence around dipstick in NLUTD (only negative dipstick results are informative), past work on the SCI International UTI Basic Dataset using the USQNB, and international consensus on cUTI guidelines. Additionally, this team has completed work on dipstick assessment that supports the IDSA Guideline on utility of negative dipstick (i.e., N=negative and LE=zero or trace) only. Individuals who meet the definition of "presumed UTI" will, present to clinic for urine collection, and will be prescribed antibiotics to treat the UTI. After completion of the antibiotics, participants will have completed the study. A total of 100 urine samples will be collected, 50 urine samples from the new catheter (to be used for prescribing) and 50 urine samples from the bag (urine from the same participant) from the IDC population. Each of these urine samples will be divided into three aliquots for analysis as described below. Day 0 Assessment: Immediately after a patient is identified as a Screen Pass (Presumed UTI on USQNB), urine samples will be collected and divided into 3 aliquots for: 1. Dipstick, urinalysis and SUC by the Medstar clinical microbiology lab; 2. Assessment by Jiddu, obtaining uRRR value and pooled phenotypic AST results; and 3. Biobanking at -80°C for current and future analyses related to UTI diagnostics Urine Sample Collection For participants who are considered Screen Pass (Presumed UTI on USQNB), two urine samples will be collected. The first sample will be obtained directly from the bladder immediately after replacing the indwelling catheter (IDC). The second sample will be collected from the original drainage bag attached to the IDC present upon presentation to the clinic. Antibiotic Initiation (Day 0): Standard of Care (SoC) Empiric Antibiotic Determination: Empiric antibiotic choice will be made by the study clinician using patient-specific previous SUC results, if available. Availability of previous SUC results will be recorded and empiric antibiotic choice will be recorded but not prescribed (recorded as SoC-empiric antibiotic choice, and use of prior SUC results for this decision will also be recorded). Jiddu-determined pooled phentotypic AST Antibiotic Determination: Jiddu-determined pooled-AST will be determined from the bladder urine sample for IDC (directly from the bladder for IDC). This result will be used for antibiotic determination; this takes approximately 60 minutes. The results ("resistant" or "non-resistant") of each antibiotic pooled-AST will be recorded. If Jiddu-determined pooled-AST results reveal non-resistance to more than one antibiotic, choice of antibiotic to be prescribed will follow these criteria: 1. If previous SUC and AST results are available, the same or similar class antibiotic will be prescribed (unless it required change to another antibiotic); and 2. Genitourinary-specific spectrum antibiotic will be used. The clinician will use their best judgement and all available evidence, including the Jiddu-determined pooled-AST results, and prescribe 7 days antibiotic treatment (prescription will be recorded). Days 1-7 Monitoring During Antibiotic Treatment Period: Symptoms will be monitored and recorded during the antibiotic treatment period. The USQNB will be readministered on day 3 and 7 during following initiation of treatment through automatic emails from REDCap. SUC results and SUC-based ASTs will be available between 72-96 hours after study initiation. Results will be recorded. A clinical research assistant (not the study clinician) will record cases where the SoC SUC-based AST characterizes the identified pathogen(s) to be resistant to the Jiddu-determined pooled phenotypic AST treatment. Need for rescue antibiotics: Study personnel will contact participants between 72-96 hours after the initiation of antibiotic treatment (CRC symptom check) and after SUC-based AST results are available. In cases where symptoms have increased in number, or if the combination of number and type of symptoms has put the patient's risk of UTI level into a greater likelihood category, then Jiddu-determined antibiotics will be discontinued and rescue antibiotics (determined by SUC-based AST) will be prescribed (for an additional 7 days). If rescue antibiotics are used, the 7-day USQNB follow up period will restart. Day 10 Monitoring During Post-Antibiotic Treatment Period: Symptoms will be monitored and recorded at the completion of antibiotics on day 10 after antibiotic completion, through automatic emails from REDCap. Day 0 assessment if Screen fail If participants fail screening from USQNB questionnaires by not meeting the criteria for UTI per USQNB (high or moderate likelihood UTI profile), he or she will be considered a screen fail. Participants who screen fail will repeat the USQNB on days 3 and 7, or if new symptoms occur at any point during the 7 days following screening (monitoring will be using REDCap). If their symptom profile does not change to meet screen pass criteria during this period, they will continue to be in the study and will continue to be able to complete the USQNB thereafter if they have concerns for a UTI. Individuals who screen fail for UTI can continue to participate in the full 6 month study.