Background & Objective(s): Antimicrobial resistance due to extended-spectrum β-lactamase (ESBL) production is a major public health issue. Its rapid detection is critical for early appropriate antibiotic use to prevent treatment failure, especially in cases of septicemia requiring appropriate empiric antibiotic therapy within the first few hours, thereby decreasing the mortality rate. Rapid detection is also important to spare the use of carbapenems, which, if used as a first-line drug in antibiotic policies, may lead to the emergence and spread of carbapenemases. We evaluated the Nordmann–Dortet–Poirel (NDP) test as a rapid method to detect ESBL producers directly from urine samples from patients with symptomatic urinary tract infections (SUTIs). Furthermore, we determined the clinical and economic outcomes of using NDP test results to guide antibiotic therapy. Methods: This cross-sectional study and double-blind, randomized control trial was conducted over 10 months. Urine samples were collected randomly from all patients with urinary tract infections admitted to the Internal Medicine Department at Alexandria University Hospital during the study period and assessed for eligibility. We enrolled 152 SUTI patients with gram-negative bacilli (≥105 cfu/ml), and the samples were tested for ESBLs using modified double-disk synergy testing (MDDST) and the NDP test. Patients were randomly divided into groups A or B, where culture-based therapy or NDP test-guided therapy was used first, respectively. All patients were observed for a clinical cure for at least 5 days. Results: The prevalence of ESBLs was 50% using MDDST. The overall sensitivity, specificity, positive predictive value, negative predictive value, and total accuracy for the ESBL NDP test performed directly on urine samples, using interpretable results, were 89.86%, 62.86%, 70.45%, 86.27%, and 76.26%, respectively. There was moderate agreement between the NDP test and MDDST and a statistically significant reduction in the length of antibiotic therapy (LOT) in the group using NDP test-guided therapy (p = 0.0002). Conclusion: The NDP test is a rapid and easy ESBL detection method that could be introduced in clinical practice. It is useful in guiding empiric therapy and reducing the LOT. A combination of ESBL NDP and Carba NP tests could be used in areas with a high prevalence of carbapenemases and ESBLs, but further studies are necessary to confirm efficacy.