Fosfomycin IV Dosing for Severe UTI
For severe urinary tract infections, intravenous fosfomycin should be dosed at 6 grams every 8 hours for 7 days, or 14 days if concurrent bacteremia is present. 1
Standard IV Dosing Regimen
- 6 grams IV every 8 hours (total daily dose of 18 grams) is the evidence-based regimen for complicated upper urinary tract infections and severe UTIs 1, 2
- Treatment duration is 7 days for complicated UTI without bacteremia 1
- Extend to 14 days if concurrent bacteremia is documented 1
This dosing is derived from the ZEUS Phase 2/3 clinical trial, which demonstrated that IV fosfomycin was noninferior to piperacillin-tazobactam for complicated upper UTIs and actually superior for complicated lower UTIs, with excellent microbiological eradication rates against multidrug-resistant organisms including ESBL-producing E. coli and carbapenem-resistant Enterobacterales 1.
Alternative Dosing for Non-Critically Ill Patients
- 4 grams IV every 6 hours is supported by pharmacokinetic/pharmacodynamic studies in non-critically ill patients with bacteremic UTI caused by multidrug-resistant E. coli 3
- This regimen achieved adequate target attainment for 1-log bacterial burden reduction in 89-96% of patients when using EUCAST breakpoints 3
- Higher doses (8g every 8 hours) showed only mild improvement over 4g every 6 hours but may increase toxicity without significantly improving efficacy 3
Key Clinical Considerations
When to Use IV Fosfomycin:
- Severe complicated UTI or acute pyelonephritis requiring hospitalization 1, 2
- Infections caused by multidrug-resistant Gram-negative organisms (ESBL, CRE, aminoglycoside-resistant) 1, 4
- Patients who have failed first-line therapy 1
- Documented susceptibility to fosfomycin in resistant organisms 4
Important Caveats:
- Fosfomycin concentrations are highly variable between patients, partially explained by renal function 3
- The drug is primarily renally excreted, requiring dose adjustment in renal impairment 4
- Do not use for complicated intra-abdominal infections with septic shock - guidelines specifically exclude this scenario 4
- Susceptibility testing is not routinely performed in many laboratories, so confirm availability of testing before relying on empiric coverage 4
Renal Dose Adjustments
While specific IV fosfomycin renal dosing is not well-established in the evidence provided, the drug requires monitoring in renal impairment given its renal excretion pathway 3. Baseline creatinine clearance determination is recommended 4.
Comparison to Oral Fosfomycin
Oral fosfomycin is NOT appropriate for severe UTI - it is only approved for uncomplicated cystitis 4, 1. The oral formulation (3g single dose) has lower bacterial eradication rates than other first-line agents and should be reserved for uncomplicated lower UTI 4.