Urinary tract infections (UTI), mainly driven by Gram-negative bacteria (GNB) are a frequent cause of hospitalization and the second cause of antibiotic prescription after lower respiratory tract infections. Integrons play a major role in the dissemination of antibiotic resistance among GNB. In the prospective INVICTUS project, whose ultimate objective is to reduce the use of large broad-spectrum antibiotics, our hypothesis is that, in adult patients with a non-severe UTI (qSOFA<2) and a former documentation with a 3GC-resistant GNB in the previous 6 months, integrons search could reduce the empirical use of large broad-spectrum antibiotics.

The promotor conducted a multicenter prospective study, IRIS (Interest of integrons as predictive markers of acquired antibiotic Resistance in patients with urinary or Intra-abdominal Sepsis) which showed that integrons have a high negative predictive value (NPV) for antibiotic resistance. Among the 343 patients admitted in the ED or intensive care units (ICU) with a urinary sepsis, the NPV of integrons, by detecting them directly form urine samples, was 96.6% (CI:94.0-98.6%) for resistance to 3GC. Whether the detection of integrons to predict antibiotic resistance could efficiently guide empirical antibiotic therapy of patients with a UTI remains to determine. INVICTUS aims at providing the front-line ED physician with additional valuable information using molecular detection of integrons, to best guide adequate first-line antibiotic therapy, while sparing large broad-spectrum antimicrobial agents. In the experimental arm, empirical parenteral antibiotic therapy will be guided based on the detection of integrons. If integrons detection is positive, a large broad spectrum therapy with ureidopenicillin and β-lactamase inhibitors combinations (Piperacillin-Tazobactam) or carbapenems (Imipenem, Meropenem) will be prescribed. If integrons detection is negative, patient will receive a parenteral 3GC (Ceftriaxone, Cefotaxime, Ceftazidime or Cefepime). In the control arm, the comparative treatment will be an empirical antibiotic therapy with ureidopenicillin and β-lactamase inhibitors combinations (Piperacillin-Tazobactam) or carbapenems (Imipenem, Meropenem) at clinician's discretion. For the primary analysis, the number of days with large broad-spectrum antibiotic therapy during the first week will be compared between the two groups using a Student t-test.

Inclusion Criteria:

• Age ≥ 18 years old; Hospitalized or admitted to the Emergency department;
• Diagnosis of non-severe (qSOFA < 2) urinary tract infection coupled with fever ≥ 38°C or < 36°C
• Presence of bacteria in the fresh urine sample and/or GNB on the Gram stain
• Empirical parenteral antibiotic therapy required; Hospitalization required;
• Former documentation of a 3GC-resistant GNB on a microbiological sample in the previous six months
• Informed consent of the patient or their representative

Exclusion Criteria:

• Pregnant and/or breastfeeding
• Neutropenia (absolute neutrophil count < 500 / mm3)
• Severe UTI with sepsis (qSOFA ≥ 2) or septic shock
• Urinary derivation required (ureteral catheter/per-cutaneous nephrostomy) except for simple urinary catheterization
• Known allergy to β-lactams
• Patients with a former documentation with carbapenemase-producing Enterobacterales in the last 6 months
• Ongoing antibiotic treatment with 3GC, piperacillin-tazobactam or carbapenem
• Not affiliated to Social Security