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

Urinary Tract Infections in Children Clinical Trial

— INVICTUS PED  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05066854
• Other study ID #: 87RI20_0029 (INVICTUS PED)
• Status: Recruiting
• Phase: N/A
• Start date: October 18, 2022
• Est. completion date: November 18, 2025

Study information

• Verified date: September 2023
• Source: University Hospital, Limoges
• Contact: Christine LAGUILLE, MD
• Phone: 0555058664
• Email: christine.laguille[@]chu-limoges.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 232
• Est. completion date: November 18, 2025
• Est. primary completion date: November 18, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Months to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Communicable Diseases
• Emergencies
• Infections
• Urinary Tract Infections
• Urinary Tract Infections in Children

Intervention

Procedure:
• integron research
Patients with suspected UTI with fever will be screened at their admission to the pediatric ED. Urine samples will be sent to the laboratory for culture and integron PCR according to routine practice. Results of the integron search will be given to the investigator. Patients in the experimental group with a positive or uninterpretable PCR will also receive an empirical antibiotic treatment based on the usual practice of each center according to the GPIP guidelines. Patients in the experimental group with a negative PCR will receive a treatment with SXT at the recommended dose.
• usual practice
Patients with suspected UTI with fever will be screened at their admission to the pediatric ED. Patients in the control group will receive an empirical antibiotic treatment based on the usual practice of each center according to the GPIP guidelines.

Locations

Country	Name	City	State
France	Bordeaux university Hospital	Bordeaux
France	Limoges university Hospital	Limoges
France	Montpellier university Hospital	Montpellier
France	Toulouse university Hospital	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Limoges

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recovery	Recovery defined as, apyrexia obtained within less than 72h and no persistence or repetition of UTI with fever and no change of empirical antibiotic therapy required because of resistance and no treatment interruption for adverse effects	Day 30
Secondary	patients treated	Number of patients treated with 3GC in both groups, during the participation of each patient	Day 30
Secondary	Duration treatment	Duration of treatment with 3GC in both groups for patient treated, during the participation of each patient	Day 30
Secondary	Antibiotic treatment changes	In both groups, description of antibiotic treatment changes based on the AST results, according to 4 criteria: Change because of resistance; Narrowing of the antibiotic spectrum; Interruption because the diagnosis of UTI was ruled out; Antibiotics used	Hour 48
Secondary	Adaptation of antibiotherapy with the AST result	Proportion of patients in both groups for whom empirical antibiotic treatment was adapted to the AST results and did not require any change (because of resistance, or to narrow the antibiotic spectrum)	Hour 48
Secondary	Resistance of enterobacteria	In the study population, percentage of resistance of enterobacteria to the different antibiotic classes	Hour 48
Secondary	Predictive values of the integrons	Negative and positive predictive values of the integrons depending on the main antibiotic classes used in the experimental group.	Hour 48
Secondary	Apyrexia	Time to apyrexia from the start of the antibiotic therapy compared between both groups.	Hour 48
Secondary	Early repetition of urinary tract infection	Proportion of early repetition of urinary tract infection with fever in both groups.	Day 30
Secondary	Treatment interruption for adverse effects	Proportion of treatment interruption for adverse effects in both groups.	Day 30
Secondary	Time spent in the pediatric emergency department	Time spent in the pediatric emergency department in both groups	Day 30