One dose of intravenous antibiotics for complicated urinary tract infections in children

CHOICE UTI - Clinical Efficacy of Single Dose (Daily) IV Antibiotics Followed by 2 Days Oral Antibiotics Compared to 3 Doses (Daily) IV Antibiotics for Children With Complicated Urinary Tract Infections: a Multicentre Randomised Trial

This study is testing if giving children with complicated urinary tract infections one dose of intravenous antibiotics followed by two days of oral antibiotics works just as well as the usual three doses of intravenous antibiotics.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 452 (estimated)
• Ages: 3 Months to 18 Years
• Sex: All
• Sponsor: Murdoch Childrens Research Institute (Academic / other)
• Locations: 6 sites (Adelaide, South Australia and 5 other locations)
• Trial ID: NCT04876131 on ClinicalTrials.gov

What this trial studies

This multicentre, open-label, non-inferiority randomized controlled trial aims to compare the effectiveness of a single dose of intravenous antibiotics followed by two days of oral antibiotics against the standard three doses of intravenous antibiotics for treating complicated urinary tract infections (cUTIs) in children. The study will enroll children aged 3 months to 18 years presenting to the emergency department with specific complicated features of UTI. The primary outcome will assess symptom resolution at 72 hours post-treatment, while secondary outcomes will evaluate readmission rates due to persistent symptoms. This approach seeks to reduce unnecessary hospital stays and antibiotic exposure.

Who should consider this trial

Good fit: Ideal candidates are children aged 3 months to 18 years with complicated urinary tract infections presenting with specific symptoms such as fever, vomiting, or urological abnormalities.

Not a fit: Patients with uncomplicated urinary tract infections or those who do not meet the inclusion criteria will not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to a more efficient treatment protocol for children with complicated urinary tract infections, reducing hospital stays and antibiotic use.

How similar studies have performed: Other studies have shown success with similar approaches in treating infections, but this specific protocol is novel in its application to complicated urinary tract infections in children.

Eligibility criteria

Inclusion Criteria:

* 3 months (corrected age) to 18 years
* Fever (reported fever at home or measured fever of ≥38 degrees Celsius associated with the illness that triggered current ED presentation (eg fever may have been 18 hours prior to presentation but none since then because patient has been on maximal antipyretics - paracetamol or ibuprofen)
* Any of the following complicating features: Vomiting, Rigors, History of recurrent UTI, Urological abnormalities, Tachycardia
* Urine sample available (Urine culture must have been collected prior to or within an hour of antibiotic treatment, either at the GP or ED - in order to assess urine culture as per below).
* Abnormal urinary dipstick leucocyte esterase \>1+ or nitrite positive OR ≥5 White Blood Cells (WBCs) per high-power field in centrifuged urine OR≥ 10 White Blood Cells (WBCs) per mm3 in uncentrifuged urine and bacteriuria with any bacteria per high-power field
* ED clinician determines the child requires treatment with IV antibiotics \* In ED, only urine dipstick or urinalysis will be available. Once urine culture is available, to be included in the efficacy analysis, culture results must meet the following criteria: Positive urine culture result with no more than 2 species of microorganisms AND Spontaneously voided urine with ≥105 microorganisms per mL of urine or Suprapubic aspirate or urinary catheter with ≥104 microorganisms per mL of urine. In the absence of a positive urine culture, ultrasonographic findings supporting pyelonephritis (per reporting radiologist) will be accepted as evidence of a urinary tract infection.

Exclusion Criteria:

* Sepsis (requiring inotropic support or more than 20ml/kg of fluid bolus in Emergency Department)
* Known allergy to all once daily study drug options (gentamicin or ceftriaxone or amikacin)
* If the patient has another co-existing condition which requires (based on established evidence-based guidelines) more than 1 dose of IV antibiotics eg meningitis
* Known chronic renal failure or renal transplant patients
* Unrepaired posterior urethral valves
* Indwelling stent and fever
* Previously enrolled participants in the CHOICE UTI trial.
* No available oral antibiotic option for this UTI: urine culture result already available and multi-resistant organism with susceptibility only to IV antibiotics or known intolerance to oral antibiotics (previous UTI with multi-resistant organism not an exclusion)
* Previous IV antibiotics for same UTI episode eg interhospital transfer whereby significant time has passed since first dose IV
* Patients with clinically suspected renal abscess e.g., extreme renal tenderness, out of keeping with pyelonephritis (clinically determined).
* Clinician does not intend on prescribing a course of IV antibiotics but plans on only giving a single dose from the outset
* Recurrence of urinary tract infection within 2 weeks
* Unable to obtain consent
* Patient is pregnant

Where this trial is running

Adelaide, South Australia and 5 other locations

• Women and Children's Hospital — Adelaide, South Australia, Australia (Recruiting)
• University Hospital Geelong — Geelong, Victoria, Australia (Recruiting)
• Monash Health — Melbourne, Victoria, Australia (Recruiting)
• Royal Children's Hospital — Parkville, Victoria, Australia (Recruiting)
• Perth Children's Hospital — Perth, Washington, Australia (Recruiting)
• Starship Children's Hospital — Auckland, Auckland Province, New Zealand (Recruiting)

Study contacts

• Principal investigator: Laila Ibrahim — Murdoch Childrens Research Institute
• Study coordinator: Laila Ibrahim

Conditions Complicated Urinary Tract Infection; Infection; Pediatric Infectious Disease