Clinical trial NCT05066854: INterest of the Negative Predictive Value of Integrons in Choosing a Narrow-spectrum Empirical anTibiotic Treatment vs Usual Empirical Antibiotic Treatment for Urinary Tract infectionS in the PEDiatric Emergency Department
Official title: INterest of the Negative Predictive Value of Integrons in Choosing a Narrow-spectrum Empirical anTibiotic Treatment vs Usual Empirical Antibiotic Treatment for Urinary Tract infectionS in the PEDiatric Emergency Department
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Urinary Tract Infections in Children
Keywords: empirical antibiotic treatment
biomarker
urinary tract infection
antibiotic resistance
pediatric emergency department
Lead sponsor: University Hospital, Limoges
Sponsor class: OTHER
First posted: 2021-10-04
Enrollment: 232
Sex: ALL
Minimum age (years): 3
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: INVICTUS PED primary objective is to show the non-inferiority of an empirical antibiotic therapeutic management guided by the early detection of integrons in the urine, compared to a usual empirical antibiotic treatment, for the recovery of children admitted to the pediatric emergency department (ED) with a non-severe urinary tract infection (UTI) with fever

Detailed description: Urinary tract infections with fever are common in children and require primary health care management. Because of the risk of immediate evolution to a systemic infection with long-term renal scars, empirical antibiotic treatment is recommended. The French Group for Pediatric Infectious Diseases (GPIP) recommends the use of third-generation cephalosporins (3GC) targeting enterobacteria, which are mainly involved in UTI and increasingly resistant to antibiotics through the production of extended-spectrum β-lactamases. However, use of 3GC is a well-known risk factor for resistant germs selection and one of the main guideline to fight antibiotic resistance, which is an important public health issue, is to reduce their use. Integrons are genetic elements involved in the spread of antibiotic resistance in enterobacteria. Preliminary studies showed that integron search using polymerase chain reaction (PCR) directly on urine samples had a great NPV (\>98%) for trimethoprim-sulfamethoxazole (SXT). The hypothesis is that, in children presenting to the pediatric ED with non-severe UTI with fever, absence of integron in their urine could allow prescribing an empirical antibiotic treatment with SXT without decreasing the chance of recovery, thus decreasing the use of 3GC.

Two strategies is compare: i) In the control group: empirical antibiotic treatment according to the usual practice of each center, in line with the GPIP guidelines, ii) in the experimental group: empirical antibiotic treatment chosen depending on the results of the integron search with PCR. When PCR is positive, treatment according to usual practice; when PCR is negative, treatment with SXT.

Two follow-up visits, by phone, will be planned: at H48 (+ 24h), when the empirical antibiotic treatment is assessed based on the urine culture and antimicrobial susceptibility test (AST) results, and on D30 (+/- 2 days) at the end of the follow-up.

Eligibility criteria: Inclusion Criteria:

* Children above 3 months old and under 18 years old
* Consultation in a participating pediatric emergency department
* Suspicion of UTI with fever (Fever ≥ 38°C and urine dipstick test positive for leukocytes and/or nitrites)
* First episode of UTI with fever
* Written informed consent of the holders of parental authority
* Affiliated to Social Security

Exclusion Criteria:

* Criteria of severity:

  * Severe infection with severe sepsis or septic shock
  * Dehydration ≥ 10%
  * Fever ≥ 38°C \> 4 days (96h)
  * Indication of surgical or interventional drainage
* Complication risk factors:

  * Any anatomic or functional defect of the urinary tract (other than low-grade VUR and calyceal dilation \< 10 mm)
  * Repetition of UTI with fever ≤ than 6 months since the previous episode
  * Repetition of UTI with fever and anatomic or functional defect of the urinary tract
  * Pregnancy
  * Severely immunocompromised patient
  * Severe chronic renal failure defined as a clearance \< 30 mL/min/1.73 m2
  * Severe liver failure
* 3GC allergy
* Contra-indication to SXT:

  * G6PD deficiency
  * Treatment with methotrexate
  * Allergy to sulfonamide
* Antibiotic treatment within 48h before admission
* Empirical antibiotic treatment not recommended

Primary outcomes:
measure: Recovery
timeFrame: Day 30
Secondary outcomes:
measure: patients treated
timeFrame: Day 30
measure: Duration treatment
timeFrame: Day 30
measure: Antibiotic treatment changes
timeFrame: Hour 48
measure: Adaptation of antibiotherapy with the AST result
timeFrame: Hour 48
measure: Resistance of enterobacteria
timeFrame: Hour 48
measure: Predictive values of the integrons
timeFrame: Hour 48
measure: Apyrexia
timeFrame: Hour 48
measure: Early repetition of urinary tract infection
timeFrame: Day 30
measure: Treatment interruption for adverse effects
timeFrame: Day 30
measure: Time spent in the pediatric emergency department
timeFrame: Day 30
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Bordeaux university Hospital
city: Limoges
country: France
facility: Limoges university Hospital
city: Montpellier
country: France
facility: Montpellier university Hospital
city: Toulouse
country: France
facility: Toulouse university Hospital
Study officials:
References: