Study Overview:
Complicated urinary tract infections (cUTIs) remain a significant clinical challenge, often prompting empiric antibiotic use that may result in inappropriate therapy, antimicrobial overuse, and treatment failure. This study aimed to evaluate the clinical utility of molecular diagnostics (PCR) versus Conventional culture and sensitivity (C\&S) methods in managing cUTIs, with the goal of identifying more effective patient management strategies.
This was a randomized, parallel-group, investigator-blinded, multi-center clinical trial conducted across six sites in the United States. Adults meeting all inclusion and no exclusion criteria who provided informed consent were randomized 1:1 into two arms: PCR-guided therapy and C\&S-guided therapy. Each participant provided a urine sample before randomization, which was tested using both PCR and C\&S. However, treating investigators remained blinded to the comparator test results throughout the study to ensure unbiased clinical decision-making.
Study Protocol:
Urine specimens were collected using a clean-catch midstream method at two time points: Day 1 (baseline) and Day 28 (end of study, EOS). Samples were refrigerated at 2-8°C and processed at a central lab. All specimens were split for parallel testing using:
* PCR (DocLab UTM 2.0): A qualitative panel targeting 28 uropathogen species and 16 antimicrobial resistance gene classes via QuantStudio 7/12 and KingFisher platforms.
* Conventional C\&S: Quantitative bacterial culture and sensitivity testing to identify uropathogens and assess resistance profiles, with a detection threshold of ≥10⁵ CFU/mL.
Blinding and Treatment Allocation:
Participants were treated based exclusively on the test result assigned by randomization (PCR or C\&S). Comparator test results were withheld from clinicians until after the study concluded.
The primary endpoint was the number (and percentage) of subjects in each study arm with favorable clinical outcomes (FCl) at the EOS visit. The FCl was defined as a patient's clinical response, assessed by the treating investigator, indicating either clinical improvement or cure. Clinical improvement was defined as the resolution of at least one symptom of cUTI present at baseline, absence of new cUTI symptoms, and/or avoidance of parenteral antibiotic therapy following randomization. Clinical cure was defined as the complete resolution of all acute signs and symptoms of cUTI present at baseline, to the extent that no further antimicrobial therapy (either IV or oral) was required for the treatment of the cUTI.
The secondary endpoint included several assessments:
* Number (and percentage) of subjects with microbiological eradication at the EOS, defined as achieving a quantitative urine culture at the EOS indicating a reduction of all uro-pathogens present at baseline to \<10\^5 colony forming unit per milliliter (CFU/mL) and the absence of baseline pathogens detected by EOS urine PCR (Cq \> 33);
* Subjective measurement of treating investigator satisfaction score through a questionnaire (5 questions) at EOS, evaluated factors such as (1) result availability/timeliness, (2) clarity of result interpretation, (3) clinical decision-making utility, (4) overall test satisfaction, and (5) perceived impact on patient outcomes versus comparator.
* Comparison of turnaround time between molecular diagnostic procedures and conventional diagnostic
* Overall agreeability between the diagnostic results generated by PCR versus C\&S as assessed by discordant analysis
* Assessment of the favorable clinical outcome of patients with discordant results \[PCR(+), CS(-) and PCR(-), CS(+)\]
