Fosfomycin Versus Standard of Care in Children With Antibiotic-resistant Urinary Tract Infections

Condition(s) studied

Investigational drug(s) / intervention(s)

Fosfomycin: Fosfomycin trometamol is a white crystalline powder which is very soluble in water. The granules are mixed with 90ml of cool water for the constitution to dissolve and will be administered soon after reconstitution. Each 30ml will contain 1g fosfomycin base. * Children ≥ 6 months to \<1 year old will be administered 30ml (=1g fosfomycin base) of dissolved solution and the remainder discarded for each dose. * Children ≥ 1 to 11 years will be administered 60ml (=2g fosfomycin base) of dissolved solution and the remainder discarded for each dose. * Children ≥12 and \<18 years will be administered the entire 90ml solution (= 3g fosfomycin base) for each dose.

Standard of care antibiotics: Standard of care antibiotics will be chosen by the treating clinician according to institutional prescribing practices, local antibiograms and medication availability.

Study summary

Urinary tract infections (UTIs) are among the most common bacterial infections in children. Up to 50% of UTI's are caused by multi-drug resistant ESBL-producing gram negative bacteria that do not respond to treatment with oral penicillin's or cephalosporins. Instead, children often require hospital admission to receive broad-spectrum intravenous antibiotics when they may otherwise be safely managed at home; resulting in prolonged hospital stays and an increased use of health resources. Fosfomycin is a broad-spectrum antibiotic discovered in 1969 that remains susceptible to a large number of organisms due to its low international use. Fosfomycin can be prepared as an oral solution with an orange/tangerine flavour and is currently approved for use in females \>12 years old. Despite extensive evidence of its efficacy in adults and safety in neonates, the use of fosfomycin in children remains limited and fosfomycin is not currently licensed for use in children \<12 years old in Australia.

The aim of this clinical trial is to compare the use of oral fosfomycin against standard of care antibiotics for the treatment of antibiotic resistant urinary tract infections in children. The main questions the trial aims to answer are:

1. Is oral fosfomycin non-inferior in efficacy to the current standard of care for the treatment of antibiotic-resistant urinary tract infections in children?
2. Is oral fosfomycin a safe and well-tolerated antibiotic in children?
3. What is the best dosing regimen of oral fosfomycin for the treatment of antibiotic-resistant UTIs in children?

Eligibility

Primary outcome measure(s)

• Treatment failure within 28 days after enrolment between patients treated with standard of care versus oral fosfomycin. — 28 days
  Treatment failure is defined as: 1. Persistent or recurrent (clinical and microbiologically-confirmed) diagnosis of a UTI between 7 and 28 days after enrolment, with the same uropathogen; or 2. Decision to switch to an alternative antibiotic due to perceived treatment failure; or 3. Isolation of the same pathogenic organism from a new sterile site between 7 and 28 days after enrolment;

Trial sites (5)

More University of Sydney trials in Australia