Clinical bottom line
Intravenous fosfomycin is emerging as a promising option for early treatment of multidrug-resistant (MDR) urinary tract infections (UTIs) in the emergency department (ED) setting, particularly when caused by resistant Gram-negative pathogens. While oral fosfomycin has established utility for uncomplicated UTIs, intravenous formulations may offer enhanced efficacy for complicated or severe infections presenting acutely. Current evidence suggests intravenous fosfomycin has a favorable safety profile and broad-spectrum activity, including against extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. However, clinical data remain limited, and its role as first-line therapy in the ED requires further validation through prospective studies.
What the evidence shows
Multidrug-resistant UTIs are an increasing challenge in emergency care, with prevalence rising globally and associated with worse outcomes (Khawcharoenporn et al., 2013; Bhatia et al., 2018). Traditional empiric antibiotics often fail against resistant pathogens, necessitating alternative agents.
Fosfomycin, a phosphonic acid derivative antibiotic, inhibits bacterial cell wall synthesis and retains activity against many MDR Gram-negative bacteria, including ESBL producers (Harris et al., 2019). Oral fosfomycin trometamol is widely used for uncomplicated cystitis, but intravenous fosfomycin formulations have been developed for systemic infections and complicated UTIs.
Harris et al. (2019) reviewed intravenous fosfomycin’s potential in complicated UTIs, highlighting its broad spectrum, low toxicity, and synergy with other antibiotics. Clinical experience, primarily from Europe and Asia, supports its use in severe infections caused by MDR pathogens, often as part of combination therapy. Bouiller et al. (2022) demonstrated oral fosfomycin’s efficacy in male patients with MDR Enterobacterales UTIs, suggesting systemic fosfomycin could be effective in more severe cases.
Moore et al. (2015) reported successful use of oral fosfomycin in veterans with MDR Gram-negative UTIs, indicating its utility in resistant infections. However, intravenous fosfomycin’s pharmacokinetics allow higher serum and urinary concentrations, potentially improving outcomes in complicated infections presenting to the ED.
Safety data are reassuring, with low rates of adverse events reported (Harris et al., 2019). The 2026 Reactions Weekly report noted fosfomycin’s combination with meropenem as well tolerated, supporting its use in severe infections requiring broad coverage.
Caveats and uncertainty
Despite promising data, robust randomized controlled trials (RCTs) specifically evaluating intravenous fosfomycin in the ED for MDR UTIs are lacking. Most evidence derives from retrospective cohorts, case series, or extrapolation from oral fosfomycin studies and complicated infection management outside the ED.
Resistance to fosfomycin can develop, especially with monotherapy, underscoring the need for susceptibility testing and often combination regimens (Harris et al., 2019). Optimal dosing, duration, and patient selection criteria remain to be standardized.
Pediatric data are limited, though Roberts et al. (2018) highlight the burden of MDR UTIs in children presenting emergently, suggesting a potential role for fosfomycin pending further study.
Finally, intravenous fosfomycin availability varies geographically, and cost considerations may limit widespread adoption in some ED settings.
How this may change practice
For emergency clinicians facing MDR UTI cases, especially complicated presentations or those failing standard empiric therapy, intravenous fosfomycin represents a putative therapeutic option warranting consideration. Early initiation in the ED could improve pathogen clearance and reduce progression to severe sepsis or hospitalization.
Incorporating fosfomycin into local antibiograms and stewardship protocols may optimize empiric choices for suspected MDR infections. Emergency departments should collaborate with infectious disease specialists and microbiology to guide fosfomycin use based on local resistance patterns and susceptibility results.
Prospective studies and clinical trials are needed to define intravenous fosfomycin’s precise role, dosing strategies, and comparative effectiveness versus other agents in the ED context. Until then, its use should be individualized, balancing potential benefits against limited high-quality evidence.