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

Official title

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

Overview

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.

Detailed description

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.

Interventions

• Diagnostic test Detection of integrons
  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.
• Other Gold standard
  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 outcome measures

• Number of days with large broad-spectrum antibiotic therapy [Time frame: Day 7]

Secondary outcome measures (4)

• Proportion of patients with clinical resolution of UTI [Time frame: Day 7]
• Proportion of patients for whom the empirical antibiotic therapy [Time frame: Day 7]
• Proportion of patients, for whom the integron detection result was consistent with the AST [Time frame: Day 7]
• Proportion of resistant bacteria for the clinically-relevant antibiotics [Time frame: Day 7]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

France · 7 centers

• CHRU Tours, Hôpital Trousseau — Chambray-lès-Tours
• Grenoble university hospital — La Tronche
• Limoges university hospital — Limoges
• Hopital lariboisière — Paris
• Hôpital Saint Louis - APHP — Paris
• Groupe Hospitalier Universitaire Bichat-Claude Bernard - APHP — Paris
• CHU de Reims — Reims

Identifiers

NCT: NCT07675018 · 87RI19_0037 (INVICTUS) · ReCH-MIE-24-003 · 2026-A00508-43

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗