3-day IV Antibiotic Treatment Versus 3-day IV Followed by 7-day Oral Antibiotic Treatment for AP in Children

• Status: Not yet recruiting
• Trial end date: 2025-06-01
• Target enrollment: 0
• Participant gender: All

Summary

Antibiotic therapies currently recommended for the treatment of acute pyelonephritis (AP) in children, whether fully by the oral route or initially intravenous (IV, 3 days) followed by the oral route, have a duration of 7 to 14 days (10 days in France).

In children with no prior urological malformation, the global clinical and microbiological cure rate after antibiotic treatment completion is around 95%. Recurrence occurs in less than 5% of cases in the 3 months following AP. Renal scarring, when documented, concerns 15% of children 6 months after treatment. Renal scarring can be associated with chronic renal disease.

We hypothesize that 3 days of IV treatment is equivalent to extending to 10 days with an oral therapy to prevent long-term renal scarring.

We also hypothesize that while achieving equivalent clinical and microbiological success, and prevention of re-infections in the following 3 months, 3 days of IV treatment reduces the risk of acquisition of resistant strains of Enterobacteriaceae and increases the gut microbotia diversity compared to extending to 10 days with an oral therapy.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Treatments: Anti-Bacterial Agents

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) AND Gram-negative rods in Gram-stained urine

• Initial treatment by either ceftriaxone AND/OR amikacin

• Outpatient or hospitalised

Non-inclusion Criteria:

• Urine collected by bag

• Urine culture growing more than one bacteria

• Catheter-associated AP

• 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 (<40µmol/L before 1 year, <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 (include cephalosporin et beta-lactams) and amikacin (include aminoside)

• Known hypersensitivity to at least one of the active substances /excipients:

cotrimoxazole (=sulfamethoxazole/trimethoprim) (include sulfonamide) and cefixime (include cephalosporin)

• Known hypersensitivity to 99mTc-DMSA (medicinal product used for renal scintigraphy)

• 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 bacteria ≥ 10^4 UFC/mL

• Favorable clinical outcome at day 3 defined by temperature < 38°C at day 3 and absence of fever measured > 38°C for at least 12 hours AND no abdominal pain AND no feeding problem

• 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 D3

• No more than 1 type of bacteria

• No bacteria resistant to the initial antibiotic treatment AND cefixime OR cotrimoxazole