Urinary Tract Infections in Children
Conditions
Keywords
empirical antibiotic treatment, biomarker, urinary tract infection, antibiotic resistance, pediatric emergency department
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.
Interventions
PROCEDUREintegron 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.
PROCEDUREusual 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.
Sponsors
University Hospital, Limoges
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Months to 18 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recovery | Day 30 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration treatment | Day 30 | Duration of treatment with 3GC in both groups for patient treated, during the participation of each patient |
| Antibiotic treatment changes | Hour 48 | 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 |
| Adaptation of antibiotherapy with the AST result | Hour 48 | 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) |
| Resistance of enterobacteria | Hour 48 | In the study population, percentage of resistance of enterobacteria to the different antibiotic classes |
| patients treated | Day 30 | Number of patients treated with 3GC in both groups, during the participation of each patient |
| Apyrexia | Hour 48 | Time to apyrexia from the start of the antibiotic therapy compared between both groups. |
| Early repetition of urinary tract infection | Day 30 | Proportion of early repetition of urinary tract infection with fever in both groups. |
| Treatment interruption for adverse effects | Day 30 | Proportion of treatment interruption for adverse effects in both groups. |
| Time spent in the pediatric emergency department | Day 30 | Time spent in the pediatric emergency department in both groups |
| Predictive values of the integrons | Hour 48 | Negative and positive predictive values of the integrons depending on the main antibiotic classes used in the experimental group. |
Countries
France
Outcome results
None listed