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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Biomarkers; Urinary Tract Infections (UTI's); Drug Resistance, Microbial; Antibacterial Agents
• Intervention / Treatment: Diagnostic test: Detection of integrons; Other: Gold standard

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.

• Study Type: Interventional
• Enrollment (Estimated): 204
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Olivier BARRAUD, MD; Phone Number: +33 055505665; Email: olivier.barraud@chu-limoges.fr

Study Locations

• France
  • Chambray-lès-Tours, France, 37170
    • CHRU Tours, Hôpital Trousseau
    • Principal Investigator: Geoffroy ROUSSEAU, MD
    • Contact: Geoffroy ROUSSEAU, MD; Phone Number: +33 0247474747; Email: geoffroy.rousseau@chu-tours.fr
  • La Tronche, France, 38700
    • Grenoble university hospital
  • Limoges, France, 87042
    • Limoges university hospital
  • Paris, France, 75010
    • Hôpital Lariboisière
  • Paris, France, 75010
    • Hôpital Saint Louis - APHP
    • Contact: Olivier Peyrony, MD; Phone Number: +33 0667986515; Email: olivier.peyrony@aphp.fr
    • Principal Investigator: Olivier PEYRONY, MD
  • Paris, France, 75018
    • Groupe Hospitalier Universitaire Bichat-Claude Bernard - APHP
    • Contact: Christophe CHOQUET, MD; Phone Number: +33 0140256012; Email: christophe.choquet@aphp.fr
    • Principal Investigator: Christophe CHOQUET, MD
  • Reims, France, 51100
    • CHU de Reims
    • Principal Investigator: Stéphane GENNAI, MD
    • Contact: Stéphane GENNAI, MD; Phone Number: 0326832565; Email: sgennai@chu-reims.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Empirical parenteral antibiotic therapy based on the detection of integrons; 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). The treatment will be started after the integron detection	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.
Active Comparator: Empirical antibiotic therapy with ureidopenicillin and β-lactamase inhibitors combinations; 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. The treatment will be started after the randomization	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of days with large broad-spectrum antibiotic therapy	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	Day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with clinical resolution of UTI	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	Day 7
Proportion of patients for whom the empirical antibiotic therapy	Proportion of patients for whom the empirical antibiotic therapy was adapted to the AST	Day 7
Proportion of patients, for whom the integron detection result was consistent with the AST	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)	Day 7
Proportion of resistant bacteria for the clinically-relevant antibiotics	Proportion of resistant bacteria for the clinically-relevant antibiotics (AST data)	Day 7

Collaborators and Investigators

• Sponsor: University Hospital, Limoges

Study record dates

Study Major Dates

• Study Start (Estimated): September 15, 2026
• Primary Completion (Estimated): September 21, 2028
• Study Completion (Estimated): September 21, 2028

Study Registration Dates

• First Submitted: June 23, 2026
• First Submitted That Met QC Criteria: June 23, 2026
• First Posted (Actual): June 30, 2026

Study Record Updates

• Last Update Posted (Actual): July 1, 2026
• Last Update Submitted That Met QC Criteria: June 29, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Urinary Tract Infections; Antimicrobial Stewardship; Antimicrobial Resistance; Integron
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Infections; Urinary Tract Infections
• Other Study ID Numbers: 87RI19_0037 (INVICTUS); ReCH-MIE-24-003 (Other Grant/Funding Number: DGOS); 2026-A00508-43 (Other Identifier: ID-RCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No