INterest of the Negative Predictive Value of Integrons in the reduCtion of Large Broad-spectrum anTibiotics Consumption for Urinary Tract infectionS

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.

• Detection of integrons (Diagnostic test): 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). The treatment will be started after the integron detection.
• Gold standard (Other): 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. The treatment will be started after the randomization

Primary outcomes

• Number of days with large broad-spectrum antibiotic therapy [Day 7]: Number of days with large broad-spectrum antibiotic therapy (ureidopenicillin and β-lactamases inhibitor combinations or carbapenems) during the first week of treatment (i.e., until Day 7 after admission) in the experimental arm compared to the number of days with large broad-spectrum antibiotic therapy in the control arm

Secondary outcomes

• Proportion of patients with clinical resolution of UTI [Day 7]: Proportion of patients with clinical resolution of UTI, i.e. 2 consecutive temperature assessment < 38°C and ≥ 36°C (with a minimum interval of 3 hours) within the first 48 hours after the first parenteral antibiotic administration
• Proportion of patients for whom the empirical antibiotic therapy [Day 7]: Proportion of patients for whom the empirical antibiotic therapy was adapted to the AST
• Proportion of patients, for whom the integron detection result was consistent with the AST [Day 7]: Proportion of patients, in the experimental arm, for whom the integron detection result was consistent with the AST (i.e., true positives + true negatives, AST being the gold standard)
• Proportion of resistant bacteria for the clinically-relevant antibiotics [Day 7]: Proportion of resistant bacteria for the clinically-relevant antibiotics (AST data)

Sex: All, ages: 18 Years to any

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