AimIn severe urinary tract infection (UTI), susceptible antibiotics should be given. With the recent increase of multidrug‐resistant bacteria, especially extended spectrum beta‐lactamase producing Enterobacteriaceae (ESBL‐E), broad‐spectrum antibiotics, such as carbapenems, are used more frequently, which could lead to a further increase of multidrug‐resistant bacteria. We aimed to analyze the relationship between initial empirical antibiotic appropriateness and clinical outcomes in UTI, especially in patients with systemic inflammatory response syndrome (SIRS) and ESBL‐E.MethodsA retrospective observational study from 2012 to 2017.ResultsAmong urine culture‐positive cases with ≥105 colony‐forming units/mL (n = 1,880), true UTI cases were extracted (n = 844) and divided into the SIRS group (n = 336 [ESBL‐E12.8% (43/336)]) and non‐SIRS group (n = 508 [ESBL‐E12.6% (64/508)]). In the SIRS ESBL‐E group, the initial antibiotics were susceptible in 55.8% (24/43), among which 91.7% (22/24) improved and 8.3% (2/24) deteriorated or died. The initial antibiotics were resistant in 44.2% (19/43), among which 47.4% (9/19) improved with the initial antibiotics, 47.4% (9/19) improved after escalating antibiotics, and 5.3% (1/19) deteriorated or died. In the SIRS group, 14 cases had true bacteremia with ESBL‐E. Seven cases were initiated with inappropriate antibiotics; four cases showed improvement before or without antibiotic change and three cases improved after antibiotic escalation.ConclusionInitiation of narrow‐spectrum antibiotics in septic UTI with ESBL‐E might not deteriorate the clinical outcome if promptly escalated on clinical deterioration or with ESBL‐E culture results. Further investigation is warranted to guide judicious use of initial antibiotics.