The standard urine culture and sensitivity test is currently the gold standard for UTI diagnosis and antimicrobial susceptibility testing. Unfortunately, Standard Urine Culture (SUC) has significant limitations that negatively impact the clinical management of patients suffering from recurrent, persistent, or other complicated UTIs.
The limitations of urine culture and sensitivity testing include the inability to detect slow-growing, fastidious, or non-aerobic microorganisms as SUC has a profound detection bias for fast-growing Gram-negative aerobic organisms.
SUC, due to its selective media, fails to identify the underlying Gram-positive microorganisms along with all microorganisms that make up a polymicrobial infection (1-3).
Antibiotic sensitivity testing based on SUC, therefore, fails to take into account the presence of multiple organisms and their potential to share antibiotic resistance characteristics.
Four studies prospectively or retrospectively validated Guidance® as a more useful diagnostic tool for UTI than the current gold standard of urine culture and sensitivity testing (4-7).
Safety Study: Urine Culture And Sensitivity vs Guidance UTI
Wojno K. et al. (2019) reported the results of a retrospective study consisting of 582 consecutive elderly patients with an average age of 77 years presenting with symptoms of lower UTI. They compared the Guidance® and SUC, which were run in parallel.
How Guidance® Compared With Standard Urine Culture
Guidance® detected uropathogens in 326 patients (56%, 326/582), while SUC detected uropathogens in 217 patients (37%, 217/582).
Guidance® and SUC agreed in 74% of cases (431/582), and disagreed in 26% of cases (151/582): Guidance® was positive while SUC was negative in 22% of cases (130/582), and SUC was positive while PCR was negative in 4% of cases (21/582).
Polymicrobial infections were reported in 175 patients (30%, 175/582), with Guidance® reporting 166 and standard urine culture reporting only 39. Polymicrobial infections were identified by Guidance® in 67 patients (12%, 67/582), in which SUC results were negative (4).
Guidance® UTI Improved Clinical Information
Vollstedt A et al. (2020) conducted a prospective study to further compare Guidance® with SUC to detect and identify bacteria in UTI-symptomatic patients.
A total of 2,511 patients with UTI symptoms and an average age of 73 years were enrolled.
Guidance® and SUC identified bacteria in 62.7% (1,575/2,511) and 43.7% (1,098/2,511) of cases, respectively. SUC detected 21 bacteria, 18 of which were also detected by Guidance® with higher detection rates, especially for the Gram-positive species.
Guidance® detected 24 bacteria, among which SUC failed to detect 6, including five Gram-positive bacteria and one Gram-negative bacterium.
A total of 590 patients (23.5%) were detected by Guidance® to have at least 1 of the six bacteria.
Polymicrobial Urinary Tract Infection
A total of 861 polymicrobial infections were reported, with Guidance® reporting 834 (96.9%) and SUC reporting only 168 (19.5%). Polymicrobial detections constituted 34.3% (861/2,511) of the total patients, 53.0% of Guidance® positives (834/1575), but only 15.3% of SUC positives (167/1,098).
A. schaalii, not detected by SUC, was the most common bacterium [53.0% (442/834)] detected in polymicrobial infections by Guidance®. The three bacterial species detected by SUC but not detected by Guidance®, including Enterobacter species, the Enterococcus species, and several other rarely detected species, detected in 0.9%, 0.2%, and 0.9%, of all patients, respectively, were not included in the Guidance® assay at the time of the study (5).
Pathnostics plans to cover Enterococcus and Enterobacter species onto the Guidance® panel.
Guidance® Provides Faster Results Than Urine Culture And Sensitivity Testing
The Vollstedt A. et al. (2020) study also showed that Guidance® takes an average of 29.7 hours (9 hours less than standard urine culture and sensitivity testing) to provide physicians with urine pathogen and drug susceptibility results.
This difference increased to a median of 19 hours (34.5 hours and 53.7 hours, for Guidance® and SUC, respectively) for patients with both positive pathogen identification and susceptibility results. The faster turnaround time also means physicians have more information to treat patients faster when compared to standard urine culture and sensitivity (5).
The above two studies have demonstrated the superior ability of Guidance® to quickly detect overall more bacteria, especially Gram-positive bacteria, along with more polymicrobial infections in patients with UTI symptoms (4,5).
Improved Susceptibility Test Results When Compared To Urine Culture And Sensitivity
Vollstedt A et al. (2020) studied the interactions of bacteria in polymicrobial UTIs. A total of 758 UTI-symptomatic patients with polymicrobial bacterial samples and antibiotic susceptibility results from the Guidance® assay were analyzed.
The analyses revealed that odds of resistance to ampicillin (p = 0.005), amoxicillin/clavulanate (p = 0.008), five different cephalosporins, vancomycin (p = <0.0001), and tetracycline (p = 0.010) increased with each additional bacterial species present in a polymicrobial specimen.
In contrast, the odds of resistance to piperacillin/tazobactam decreased by 75% for each additional species present (95% CI 0.61, 0.94, p = 0.010).
For one or more antibiotics tested, thirteen pairs of bacterial species exhibited statistically significant interactions compared with the expected resistance rate obtained with the Highest Single Agent Principle and Union Principle.
These results have demonstrated that bacterial interactions in polymicrobial specimens can result in antimicrobial susceptibility patterns that are not detected when bacterial isolates are tested by themselves in standard urine culture and sensitivity testing (6).
The antibiotic susceptibility test in the Guidance® assay is a Pooled Antimicrobial Susceptibility Test (P-AST), which involves simultaneously growing all detected bacteria together in the presence of antibiotics and then measuring susceptibility. Therefore, unlike standard urine culture and sensitivity, the Guidance® assay can detect bacterial interactions in polymicrobial specimens (6).
Keeping Patients out of the Hospital
Daly A et al. (2020) clinically validated the Guidance® assay with a retrospective study of existing data from 66,383 patients seen for possible urinary tract infections by house-call primary care providers.
The clinical outcomes measured in the study were numbers of hospital admission and/or emergency department utilization. Patients were divided into two non-overlapping cohorts.
Patients in cohort one (N=34,414) were treated based upon the results from standard urine culture and sensitivity testing. The other cohort (N=31,967) was treated in accordance with results from the Guidance® assay.
The patients in the two cohorts had similar demographics, comorbidity, Charlson/Deyo Index Scores, number of provider visits, and enrollment locations, as the standardized differences were less than 0.20 for all the variables mentioned above.
They found that the use of the Guidance® assay was associated with a 13.7% decrease in hospital admissions and/or emergency department (ED) utilization compared to the use of standard urine culture and sensitivity testing (3.27% vs. 3.79%; p = 0.003).
The 13.7% reduction in hospitalization when normalized to 34,414 patients would result in a 156 patient decrease in ED/hospitalizations and/or ED utilization. These findings have demonstrated that the use of the Guidance® assay in the outpatient management of suspected urinary tract infections may improve patient outcomes and reduce emergency department and hospital utilization (7).
Urine Culture And Sensitivity vs. Guidance®: In Summary
In summary, the Guidance® assay can detect overall more bacteria, especially Gram-positive bacteria, and more polymicrobial infections in patients with UTI symptoms, with shorter turnaround time, and is associated with a decrease in hospital admissions and/or emergency department utilization, when compared to standard urine culture and sensitivity testing, the current gold standard (4-7).
- Price TK, Hilt EE, Dune TJ, Mueller ER, Wolfe AJ, Brubaker L. Urine trouble: should we think differently about UTI?. Int Urogynecol J. 2018;29(2):205-210. doi:10.1007/s00192-017-3528-8.
- Price TK, Dune T, Hilt EE, et al. The Clinical Urine Culture: Enhanced Techniques Improve Detection of Clinically Relevant Microorganisms. J Clin Microbiol. 2016;54(5):1216-1222. doi:10.1128/JCM.00044-16
- Wolfe AJ, Toh E, Shibata N, et al. Evidence of uncultivated bacteria in the adult female bladder. J Clin Microbiol. 2012;50(4):1376-1383.
- Wojno KJ, Baunoch D, Luke N, et al. Multiplex PCR Based Urinary Tract Infection (UTI) Analysis Compared to Traditional Urine Culture in Identifying Significant Pathogens in Symptomatic Patients. Urology. 2020;136:119-126.
- Vollstedt A, Baunoch D, Wojno KJ, et al. Multisite Prospective Comparison of Multiplex Polymerase Chain Reaction Testing with Urine Culture for Diagnosis of Urinary Tract Infections in Symptomatic Patients. J Sur urology. 2020; JSU-102.
- Vollstedt A, Baunoch D, Wolfe A, et al. Bacterial Interactions as Detected by Pooled Antibiotic Susceptibility Testing (P-AST) in Polymicrobial Urine Specimens. J Sur urology. 2020; JSU-101.
- Daly A, Baunoch D, Rehling K, et al. Utilization of M-PCR and P-AST for Diagnosis and Management of Urinary Tract Infections in Home-Based Primary Care. JOJ uro & nephron. 2020; 7(2): JOJUN.MS.ID.555707.