What is the recommended Fosfomycin dose for a complicated urinary tract infection (UTI) caused by E. coli?

Fosfomycin Dosing for Complicated UTI Caused by E. coli

For complicated urinary tract infections caused by E. coli, intravenous fosfomycin at a dose of 4g every 6 hours is recommended, with the option to step down to oral fosfomycin trometamol 3g every 24-72 hours after clinical improvement. 1, 2

Intravenous Fosfomycin Regimen

• Initial treatment: 4g IV every 6 hours 2
• Duration: 5-14 days total antibiotic therapy depending on clinical response 1
• Safety consideration: Monitor for heart failure, especially in at-risk patients (8.6% risk observed in clinical trials) 1

Oral Step-down Options

• Oral fosfomycin trometamol: 3g every 24 hours 3
  • Alternative dosing: 3g every 72 hours for prophylactic treatment of recurrent UTIs 4
  • Single 3g dose is only appropriate for uncomplicated lower UTIs, not complicated infections 3

Evidence Quality and Recommendations

Intravenous fosfomycin has been evaluated in two high-quality randomized controlled trials (ZEUS and FOREST) for complicated UTIs, including those with bacteremia 1. These trials showed:

• No significant differences in clinical or microbiological cure rates compared to piperacillin-tazobactam or meropenem
• Effective against cephalosporin-resistant or ESBL-producing Enterobacterales
• High-certainty evidence supports its use in complicated UTIs with or without bacteremia

Alternative Options for Complicated UTIs with E. coli

If fosfomycin is not available or contraindicated, consider:

• Ceftazidime/avibactam: 2.5g IV q8h 1
• Meropenem/vaborbactam: 4g IV q8h 1
• Imipenem/cilastatin/relebactam: 1.25g IV q6h 1
• Aminoglycosides (for urinary source infections):
  • Gentamicin: 5-7 mg/kg/day IV once daily 1
  • Amikacin: 15 mg/kg/day IV once daily 1

Important Clinical Considerations

1. Monitoring: Assess clinical response within 48-72 hours of treatment initiation
2. Adverse events: Higher discontinuation rates due to adverse events have been reported with fosfomycin compared to other antibiotics (8.5% vs 0%) 2
3. Resistance prevention: Fosfomycin may be associated with lower rates of acquiring new resistant gram-negative bacteria compared to other antibiotics 2
4. Bioavailability: Oral fosfomycin has approximately 18% bioavailability, but achieves adequate urinary concentrations 4

Treatment Algorithm

1. Confirm diagnosis of complicated UTI with E. coli
2. Verify susceptibility to fosfomycin
3. Initiate IV fosfomycin at 4g every 6 hours
4. Assess after 48-72 hours for clinical improvement
5. If improved and able to take oral medications:
   • Switch to oral fosfomycin 3g daily
6. Complete total course of 5-14 days (depending on severity and clinical response)
7. Monitor for adverse events, particularly heart failure in at-risk patients

This approach provides effective treatment while potentially reducing the risk of selecting for resistant organisms compared to carbapenem therapy.