3-day IV antibiotics versus 3-day IV followed by 7-day oral antibiotics for acute pyelonephritis in young children
3-day Intravenous Antibiotic Treatment Versus 3-day Intravenous Followed by 7-day Oral Antibiotic Treatment for Acute Pyelonephritis in Children 1 Month to 3 Years Old: a Non-inferiority Open Randomized Multicentric Clinical Trial
This project will test whether stopping after 3 days of IV antibiotics works as well as switching to 7 days of oral antibiotics for treating acute pyelonephritis in children under 3 years old with a first urinary infection.
Quick facts
| Phase | Phase 4 |
|---|---|
| Study type | Interventional |
| Enrollment | 480 (estimated) |
| Ages | 1 Month to 3 Years |
| Sex | All |
| Sponsor | Assistance Publique - Hôpitaux de Paris Academic / other |
| Locations | 15 sites (Corbeil-Essonnes, Essonne and 14 other locations) |
| Trial ID | NCT05544565 on ClinicalTrials.gov |
What this trial studies
Children aged 1 month to under 3 years with a first episode of acute pyelonephritis confirmed by fever and a positive urine culture will receive initial IV antibiotics (ceftriaxone and/or amikacin) for three days. After the initial IV period they will either stop antibiotic therapy or continue with a 7-day oral antibiotic course, with follow-up for clinical and microbiological outcomes. Outcomes include cure rates, recurrence within three months, renal scarring at six months, acquisition of resistant Enterobacteriaceae, and gut microbiota diversity. Microbiological samples (urine and fecal/rectal swabs) and PCT assays will be collected per protocol to measure these endpoints.
Who should consider this trial
Good fit: Ideal candidates are children aged 1 month to under 3 years with a first febrile urinary tract infection meeting urine culture criteria (single Gram-negative bacillus ≥ 10^4 CFU/mL) who receive initial IV ceftriaxone and/or amikacin and have no known congenital kidney or urinary tract anomalies.
Not a fit: Children with prior urological malformations, catheter-associated infections, urine samples collected by bag, mixed bacterial cultures, recurrent UTIs, or those outside the specified age/gestational criteria are unlikely to benefit from this protocol.
Why it matters
Potential benefit: If successful, children could achieve the same cure with a shorter antibiotic course, reducing total antibiotic exposure, lowering the risk of resistant bacteria, and limiting disruption of the gut microbiome.
How similar studies have performed: Direct high-quality evidence for this exact short-course strategy in young children is limited, although some adult and outpatient pediatric data support shorter antibiotic regimens for urinary infections, making this comparison relatively novel in this population.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Age ≥ 1 month and \< 3 years * For children younger than 3 months, gestational age \> 34 WA * First episode of urinary tract infection * AP defined by temperature ≥ 38°C on day of diagnosis AND positive urinalysis (white cell counts ≥ 10\^4/mL) with a positive urine culture with one Gram- negative bacillus ≥ 104 UFC/mL. The child temperature will have to be measured with a thermometer according to the French national recommendations \[Health Insurance website (AMELI ;see: - https://www.ameli. fr/assure/sante/bons-gestes/soins/prendre-temperature); HAS (see: https://www.has-sante. fr/jcms/c\_2674284/fr/prise-en-charge-de-la-fievre-chez-l-enfant)\]. * Initial treatment by either ceftriaxone AND/OR amikacin * Outpatient or hospitalised Non-inclusion Criteria: * Urine collected by bag * Urine culture growing more than one dominant bacterium (cf section 6.2 of the protocol) * Catheter-associated acute pyelonephritis * Known congenital anomalies of the kidney and genitourinary tract (other than vesicoureteral reflux and pyelocaliceal dilatation \< 10 mm) * Previous surgery of the genitourinary tract (except circumcision in male children) * Abnormal renal function for age and weight (defined by a serum creatinine \>40µmol/L before 1 year and \>75µmol between 1 year et 3 years) * Known immunocompromising condition (e.g., HIV, primary immunodeficiency, sickle cell disease, use of chronic corticosteroids or other immunosuppressive agents) * Antibiotic prophylaxis for any reason OR antibiotic treatment in the last 7 days (except treatment administered for the AP) * Known hypersensitivity to at least one of the active substances /excipients: ceftriaxone (including other cephalosporins and other beta-lactams) and amikacin (including other aminoglycosids). * Known hypersensitivity to at least one of the active substances /excipients: cotrimoxazole (=sulfamethoxazole/trimethoprim) (including other drugs containing sulfonamides) and cefixime (including other cephalosporins) * Known blood dyscrasias (megaloblastic haematopoiesis) * Known severe hepatic insufficiency * Known G6PD deficiency * No written consent from holders of parental authority * Non-affiliation to a social security system (as beneficiary or entitled person) * Children whose follow-up is not carried out in the centre * Participation in another interventional or minimal risk trial Randomization criteria : * Three days of taking antibiotics (IV or IM) (no interruption or discontinuation) * Positive urine culture with Gram negative bacillus ≥ 10\^4 UFC/mL * Favorable clinical outcome at day of randomization (D2 or D3) defined by temperature \< 38°C at day of randomization and absence of fever measured \> 38°C for at least 12 hours AND no abdominal pain AND no feeding problem AND investigator agreement * No renal abscess AND congenital anomalies of the kidney and genitourinary tract (other than vesicoureteral reflux and pyelocaliceal dilatation \< 10 mm) on the renal ultrasound performed between D0 and day of randomization * No more than 1 type of dominant bacteria on the urine culture * Sensitivity to the initial antibiotic treatment * Sensitivity to cefixime OR cotrimoxazole
Where this trial is running
Corbeil-Essonnes, Essonne and 14 other locations
- CH Sud Francilien — Corbeil-Essonnes, Essonne, France (Not_yet_recruiting)
- Paris-Saclay hospital — Orsay, Essonne, France (Recruiting)
- Antoine Beclère Hospital — Clamart, Haut de Seine, France (Not_yet_recruiting)
- Ambroise Paré hospital — Boulogne, Hauts de Seine, France (Recruiting)
- Children-Teenager hospital — Nantes, Loire Atlantique, France (Not_yet_recruiting)
- Jeanne Flandre Hospital — Lille, Nord, France (Not_yet_recruiting)
- Robert Debré Hospital — Paris, Paris, France (Not_yet_recruiting)
- Robert Debré Hospital — Paris, Paris, France (Not_yet_recruiting)
- Meaux Hospital — Meaux, Seine et Marne, France (Not_yet_recruiting)
- Jean Verdier Hospital — Bondy, Seine St Denis, France (Not_yet_recruiting)
- Intercomunal Créteil Hospital — Créteil, Val de Marne, France (Not_yet_recruiting)
- Kremlin Bicêtre Hospital — Le Kremlin-Bicêtre, Val de Marne, France (Not_yet_recruiting)
- Andre mignot hospital — Le Chesnay, Yvelines, France (Recruiting)
- GHEF Site Marne la vallée — Jossigny, France (Not_yet_recruiting)
- CHU Toulouse — Toulouse, France (Not_yet_recruiting)
Study contacts
- Principal investigator: Jean GASCHIGNARD, PhD — Hôpital Paris-Saclay
- Study coordinator: Jean GASCHIGNARD, PhD
- Email: j.gaschignard@ghne.fr
- Phone: +33 1 69 15 96 00
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.