Fosfomycin as Oral Transition Therapy Versus Continued Intravenous β-Lactams for Complicated Urinary Tract Infections...

Area of Science:

• Infectious Diseases
• Pharmacology
• Clinical Trials

Background:

• Rising rates of complicated urinary tract infections (UTIs) caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacterales necessitate novel treatment strategies.
• Over-reliance on carbapenems for ESBL-producing Enterobacterales UTIs accelerates antimicrobial resistance, highlighting the need for effective oral transition therapies.
• Developing carbapenem-sparing options is crucial for preserving last-line agents and reducing healthcare burdens.

Purpose of the Study:

• To evaluate the noninferiority of oral fosfomycin trometamol compared to continued intravenous therapy for complicated UTIs caused by ESBL-producing Enterobacterales.
• To assess oral fosfomycin as a viable transition option for patients with complicated UTIs after initial intravenous treatment.
• To provide evidence supporting oral fosfomycin as an antibiotic stewardship strategy.

Main Methods:

• A multicenter, open-label, randomized, noninferiority trial conducted in South Korea involving adults with complicated UTIs due to ESBL-producing Enterobacterales.
• Patients received 3-7 days of intravenous antibiotics before randomization to either continued intravenous carbapenem or β-lactam/β-lactamase inhibitor therapy or oral fosfomycin trometamol (3g once daily).
• The primary outcome was clinical cure, defined by symptom resolution within 4 days post-treatment, with secondary outcomes including microbiological cure and 30-day recurrence.

Main Results:

• Noninferiority was demonstrated, with clinical cure rates of 92.8% for oral fosfomycin and 95.2% for intravenous therapy (risk difference: -2.47%; 95% CI -7.84 to 2.89).
• Microbiological cure rates were high and comparable in both groups for both urine (98.0% vs 96.6%) and blood (97.3% vs 97.5%) isolates.
• Safety profiles and 30-day outcomes, including readmission and recurrence, were similar between the oral fosfomycin and intravenous therapy groups.

Conclusions:

• Oral fosfomycin trometamol is noninferior to continued intravenous therapy for complicated UTIs caused by ESBL-producing Enterobacterales.
• Findings support the use of oral fosfomycin as an effective transition therapy, contributing to carbapenem-sparing antibiotic stewardship.
• This strategy helps preserve essential last-line antibiotics for treating challenging infections.