Fosfomycin Versus Standard of Care in Children With Antibiotic-resistant Urinary Tract Infections (FosUTI)
Urinary Tract Infections
About this trial
This is an interventional treatment trial for Urinary Tract Infections
Eligibility Criteria
Inclusion Criteria: Children aged ≥1 to <18 years with: Symptoms suggestive of a clinical diagnosis of a UTI (as per the treating clinician); AND Microbiological confirmation: Defined as a urine culture revealing pure growth of a single bacterial uropathogen [≥106 CFU/L, or ≥103 CFU/mL] together with ≥10 white blood cells [WBCs] per high power field in centrifuged urine on microscopy, or ≥10 WBCs/mm3 in uncentrifuged urine]; AND The bacterial uropathogen is one of: Escherichia coli, Proteus spp., Klebsiella spp., Enterobacter spp., Serratia spp., or Citrobacter spp., AND The uropathogen has evidence of resistance to all oral penicillins and cephalosporins AND The patient has not yet received ≥48 hours of antibiotics effective against the urinary pathogen prior to enrolment. Exclusion Criteria: Evidence of bacteraemia due to the same uropathogen within the same clinical illness; OR Evidence of infection at a secondary site (such as CNS infection or endocarditis); OR Children with features suggestive of sepsis (defined as requiring inotropic support, or >20ml/kg fluid bolus); OR Children who are unable to tolerate or absorb oral antibiotics; OR Creatinine clearance <40ml/minute; OR Known allergy to fosfomycin.
Sites / Locations
- Sydney Childrens Hospital
- Royal Childrens Hospital
- Royal Perth Hospital
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Intervention arm
Standard of Care Arm
A single dose of oral fosfomycin trometamol (Monurol), dosed as: ≥ 1 to <12 years of age: 2 grams (of fosfomycin base) as a single dose Children ≥ 12 years and <18 years of age: 3 grams (of fosfomycin base) as a single dose For children who have persistent fevers at 48 hours, the dose of oral fosfomycin may be repeated every 48 hours, to a maximum of 3 doses. For a subset of 30 children aged 1-12 years (inclusive) at the primary recruitment sites (RCH, SCH and CHW) two blood samples will be taken after the first oral fosfomycin dose to determine plasma fosfomycin concentrations. The timing of these samples after the oral fosfomycin dose are as follows, with participants being randomly allocated to one of the two sampling groups: Sample 1 Sample 2 Group 1 (n=15) 20 minutes to 180 minutes post dose 4-12 hours post dose Group 2 (n=15) 120 to 240 minutes post dose 12 to 18 hours post dose
Management as per physician preference based on institutional prescribing practices and local antibiograms. For participants administered an oral antibiotic in the Standard of Care arm, a tolerability questionnaire will be administered at the time of the first dose.