Antibacterial Agents, Biomarkers, Drug Resistance, Microbial, Urinary Tract Infections (UTI's)
Conditions
Keywords
Integron, Antimicrobial Stewardship, Antimicrobial Resistance, Urinary Tract Infections
Brief summary
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_TESTDetection 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.
OTHERGold 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
Sponsors
University Hospital, Limoges
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Multicenter, randomized, controlled, open, trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
Countries
France
Contacts
CONTACTOlivier BARRAUD, MD
Outcome results
None listed