Clinical trial NCT05819229: Oral Antibiotics Alone in Children Aged 4 Weeks to 2 Months With a Urinary Tract Infection
Official title: Oral Antibiotics Alone in Children Aged 4 Weeks to 2 Months With a Suspected or Confirmed Uncomplicated Urinary Tract Infection. A Single-arm Multicenter Prospective Observational Study.
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Urinary Tract Infections in Children
Keywords: Antibiotic therapy
Urinary tract infection
Children
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Hvidovre University Hospital
First posted: 2023-04-19
Enrollment: 125
Sex: ALL
Minimum age (years): 4
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All children aged 4 weeks to 2 months who are referred by their primary physician or the medical helpline 1813 (outside the work hours of their primary physician) to one of four pediatric emergency departments in the Capital Region of Denmark with suspected urinary tract infection.

Brief summary: The goal of this prospective study is to investigate whether oral antibiotic therapy alone is feasible and safe in clinically stable children aged 4 weeks to 2 months without any past high-risk medical history with a suspected or confirmed urinary tract infection.

Detailed description: All children aged 4 weeks to 2 months with a suspected urinary tract infection will be observed and examined by physicians and nurses as recommended by current guidelines. Children needing empirical antibiotic therapy will be admitted. The remaining will be contacted by phone if the urine culture is positive, and antibiotic therapy will be initiated if a urinary tract infection is still suspected due to persistent symptoms.

Clinically stable (see eligibility criteria) children without any past high-risk medical history (see eligibility criteria) will initiate oral antibiotic therapy. As empirical oral therapy, amoxicillin-clavulanic acid 50 mg/kg/day divided into 3 doses will be used. If the sensitivity pattern is available, a smaller-spectrum antibiotic can be used instead. If these children at any time point become clinically unstable or have a positive blood culture without suspected contamination, parenteral antibiotic therapy will be initiated. As empirical parenteral therapy, gentamicin 5 mg/kg once daily and ampicillin 100 mg/kg/day divided into 3 doses will be used. If the sensitivity pattern is available, another parenteral antibiotic regime can be used instead.

Admitted children can be sent home when they have clinically improved (judged by the physician) and have been hospitalized at least until the ward round the following day. Parents will be informed to contact the pediatric emergency department immediately if the child worsens or does not tolerate the antibiotics.

A physical or virtual follow-up will be conducted on day 3 (approximately 72 hours after treatment initiation) to ensure clinical improvement and treatment adherence. If needed, antibiotic therapy will be changed according to the sensitivity pattern. Children with a negative urine culture will be informed to stop antibiotic therapy.

The duration of antibiotic therapy will be 10 days. All children will undergo a renal ultrasound within the treatment period.

The above recommendations has been implemented as routine care. Hence, no parental consent is needed.

Eligibility criteria: INCLUSION CRITERIA:

1. Clinical suspicion of urinary tract infection irrespective of the presence of fever.
2. Clinically stable (i.e., not respiratory or circulatory affected, septic, or meningeal).
3. 4 weeks to 2 months of age (corrected age, if premature).

All children who do not receive any empirical antibiotic therapy but have a positive urine culture can be included if the clinical suspicion of urinary tract infection persists.

A positive urine culture is defined as:

* Suprapubic bladder aspiration: any growth of bacteria.
* Sterile intermittent catheterization: monoculture with ≥10\^3 colony forming units per milliliter (cfu/ml).
* Midstream urine x 2: monoculture with the same bacteria in both tests with ≥10\^4 cfu/ml.
* Midstream urine x 2: monoculture with the same bacteria in both tests with ≥10\^5 cfu/ml in one test and 10\^3 cfu/ml in another test.

EXCLUSION CRITERIA:

1. Non-Danish civil registration number.
2. High-risk medical history.

   1. Previous urinary tract infection.
   2. Prophylactic antibiotic treatment.
   3. Known urogenital abnormality (i.e., hydronephrosis (pyelectasis ≥10 mm or/and caliectasis ≥5 mm); hydroureter; vesicoureteral reflux; multicystic dysplasia; renal dysplasia; renal hypoplasia; renal agenesis; duplex kidney; ectopic placed kidneys; polycystic kidney disease; neurogenic bladder dysfunction; and hypospadias).
   4. Previous hospitalization needing antibiotic therapy.
3. Markedly elevated c-reactive protein indicating bacteremia.
4. Elevated creatinine.
5. Oral therapy is not possible (e.g., frequent vomiting or excessive regurgitation).

Primary outcomes:
measure: Proportion of participants with recurrent urinary tract infection regardless of the pathogen or death of any cause
timeFrame: Within 28 days after end of treatment
measure: Number of days admitted related to urinary tract symptoms
timeFrame: Within 28 days after treatment initiation
Secondary outcomes:
measure: Number of days with antibiotic-related non-serious adverse events.
timeFrame: From date of treatment initiation until the date of treatment stop for the baseline infection, assessed up to 14 days
measure: Proportion of participants with a recurrent urinary tract infection regardless of the pathogen or death of any cause.
timeFrame: Within 100 days after end of treatment
measure: Proportion of participants with a recurrent infection with a bacterium resistant to the antibiotic given for the baseline infection or an opportunistic infection
timeFrame: Within 100 days after end of treatment
Other outcomes:
measure: Proportion of participants with a serious adverse event.
timeFrame: Within 100 days after treatment initiation
Locations:
city: Copenhagen
country: Denmark
facility: Copenhagen University Hospital Rigshospitalet
city: Herlev
country: Denmark
facility: Copenhagen University Hospital Herlev
city: Hillerød
country: Denmark
facility: Copenhagen University Hospital Hillerød
city: Hvidovre
country: Denmark
facility: Copenhagen University Hospital Hvidovre
Study officials:
affiliation: Department of Pediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark
name: Naqash Sethi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Pediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark
name: Ulrikka Nygaard, Ass. prof, Ph.D.
role: STUDY_CHAIR
References: