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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
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Integron research | Experimental | Empirical antibiotic treatment chosen based on the results of the integron search:
|
|
| Usual practice | Other | Empirical antibiotic treatment based on the usual practice of each center according to the GPIG guidelines. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| integron research | Procedure | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| patients treated | Number of patients treated with 3GC in both groups, during the participation of each patient | Day 30 |
| Duration treatment | Duration of treatment with 3GC in both groups for patient treated, during the participation of each patient |
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Inclusion Criteria:
Exclusion Criteria:
Criteria of severity:
Complication risk factors:
3GC allergy
Contra-indication to SXT:
Antibiotic treatment within 48h before admission
Empirical antibiotic treatment not recommended
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Bordeaux university Hospital | Bordeaux | 33000 | France | |||
| Limoges university Hospital |
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| usual practice | Procedure | 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. |
|
| Day 30 |
| Antibiotic treatment changes | In both groups, description of antibiotic treatment changes based on the AST results, according to 4 criteria:
| Hour 48 |
| 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 |
| Resistance of enterobacteria | In the study population, percentage of resistance of enterobacteria to the different antibiotic classes | Hour 48 |
| 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 |
| Apyrexia | Time to apyrexia from the start of the antibiotic therapy compared between both groups. | Hour 48 |
| Early repetition of urinary tract infection | Proportion of early repetition of urinary tract infection with fever in both groups. | Day 30 |
| Treatment interruption for adverse effects | Proportion of treatment interruption for adverse effects in both groups. | Day 30 |
| Time spent in the pediatric emergency department | Time spent in the pediatric emergency department in both groups | Day 30 |
| Limoges |
| 87042 |
| France |
| Montpellier university Hospital | Montpellier | 34000 | France |
| Toulouse university Hospital | Toulouse | 31000 | France |
| ID | Term |
|---|---|
| D014552 | Urinary Tract Infections |
| ID | Term |
|---|---|
| D007239 | Infections |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
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