What is the treatment course for complicated urinary tract infection (UTI) with Fosfomycin?

Fosfomycin for Complicated UTI: Treatment Course

Fosfomycin is NOT recommended as standard therapy for complicated UTIs—it should be reserved for uncomplicated cystitis only, with the exception of specific salvage scenarios using multi-dose oral regimens (3g every 48-72 hours for 3 doses) or intravenous formulations for complicated upper tract infections. 1, 2

Standard Guideline Position

Oral fosfomycin is explicitly NOT recommended for complicated UTIs or pyelonephritis due to insufficient efficacy data. 3, 2 The major clinical guidelines consistently restrict fosfomycin to:

• Uncomplicated cystitis in women: Single 3-gram oral dose 1, 2
• Duration: One dose only for uncomplicated infections 1, 2

Exception: Salvage Therapy for Complicated Lower UTI

When first-line agents have failed, or when dealing with multidrug-resistant organisms in complicated lower urinary tract infections (not pyelonephritis), an off-label multi-dose regimen may be considered:

• Dosing: 3 grams orally every 48-72 hours for a total of 3 doses 4, 5
• Indications for this approach: 4, 5
  • Previous treatment failure with standard agents
  • Multidrug-resistant pathogens (including ESBL-producing organisms)
  • Intolerance to first-line therapies
  • Catheter-associated UTIs in select cases 6

Clinical success rates with this multi-dose regimen range from 75-96% in retrospective studies, though this represents lower-quality evidence. 5, 6

Intravenous Fosfomycin for Complicated Upper UTI

For complicated upper urinary tract infections (pyelonephritis with complications), intravenous fosfomycin represents a viable option based on the ZEUS trial:

• Dosing: 6 grams IV every 8 hours 4
• Duration: 7 days (or 14 days if concurrent bacteremia) 4
• Evidence: IV fosfomycin demonstrated superiority over piperacillin-tazobactam specifically for complicated upper UTIs, with excellent activity against ESBL-producing and carbapenem-resistant organisms 4

However, IV fosfomycin is not widely available in many countries and has not been approved by regulatory agencies including Taiwan's FDA. 1

Guideline-Recommended Alternatives for Complicated UTI

For carbapenem-resistant Enterobacterales causing complicated UTI, guidelines strongly recommend instead: 1

• Ceftazidime-avibactam: 2.5g IV every 8 hours for 5-7 days 1
• Meropenem-vaborbactam: 4g IV every 8 hours for 5-7 days 1
• Aminoglycosides: Gentamicin 5-7 mg/kg/day IV once daily or Amikacin 15 mg/kg/day IV once daily for 5-7 days 1

Critical Pitfalls to Avoid

Do not use single-dose oral fosfomycin for:

• Pyelonephritis (upper tract infection) 3, 2
• Complicated UTIs as first-line therapy 3, 2
• Men with UTIs (limited efficacy data) 2

The single-dose regimen approved for uncomplicated cystitis achieves therapeutic urinary concentrations for only 24-48 hours, which is insufficient for complicated infections requiring longer antimicrobial exposure. 1, 2

When Fosfomycin May Be Considered

For complicated UTI caused by VRE (vancomycin-resistant Enterococcus):

• Uncomplicated UTI component: 3g orally single dose or every other day 1
• Duration: 3-7 days 1
• Note: This represents a weak recommendation with very low-quality evidence 1

For complicated UTI caused by CRE (carbapenem-resistant Enterobacterales):

• Fosfomycin showed good in vitro activity and is mentioned in guidelines, but specific dosing for complicated UTI is not established 1
• The ZEUS trial data supports IV formulation for upper tract infections 1, 4

Monitoring and Follow-Up

• If symptoms persist or recur within 2 weeks: Obtain urine culture and antimicrobial susceptibility testing 3, 2
• Common adverse effects: Diarrhea, nausea, vomiting (generally mild) 3, 2
• Susceptibility testing caveat: Many laboratories do not routinely perform fosfomycin susceptibility testing, which may limit rational use 3