Fosfomycin Trometamol in the Management of Urinary Tract Infection: A Focus on Antimicrobial Susceptibility and Resistance

Urinary tract infections (UTIs) are common bacterial infections in women and vulnerable populations, with increasing incidence and prevalence worldwide. Although originally classified as uncomplicated or complicated, UTIs are now classified as localized (ie, cystitis) or systemic based on clinical signs and symptoms. Oral fosfomycin trometamol, a first-line antibiotic for localized UTIs, is active against several Gram-negative and Gram-positive bacteria, including extended-spectrum β-lactamase (ESBL)-producing Enterobacterales; however, susceptibility testing and clinical breakpoints are recommended only for Escherichia coli. Susceptibility testing is also complicated by breakpoint differences of ≤64 mg/L (CLSI) versus <8 mg/L (EUCAST). This narrative review summarizes recent data on trends in fosfomycin susceptibility and resistance across high- and low-resource settings, supporting its role in treating UTIs and informing antibiotic management strategies. Overall, studies show that urinary E. coli isolates, including ESBL-producing isolates, are highly susceptible to fosfomycin, supporting its use in treating localized UTIs. For UTIs caused by E. coli, an overall 96% susceptibility rate was identified across 13 countries, with no significant differences across high-income and lower-middle-income countries (mean fosfomycin susceptibility [min. max.] 96% [95%, 97%] vs 96.75% [85%, 100%], respectively; p=0.432). Similarly, in a European-wide cross-sectional epidemiological study of E. coli urinary isolates, >95% fosfomycin susceptibility was observed in Belgium, Spain, the United Kingdom, and Russia, versus 91.7% in Italy. Fosfomycin also appears to be an appropriate treatment option for localized UTIs in developing countries, with susceptibility rates of 78% to 100% among E. coli isolates and 85.3% to 100% among ESBL-producing E. coli isolates in India. Intracountry variation in fosfomycin susceptibility rates is observed, highlighting the importance of real-world data on local pathogen susceptibility patterns to optimize antibiotic prescribing and reduce antimicrobial resistance. Fosfomycin also shows promise in treating UTIs in vulnerable patient populations, including pediatric patients, pregnant women, men, and patients with catheter-associated UTIs.