What is the treatment for urinary tract infections caused by Extended-Spectrum Beta-Lactamase (ESBL)-producing bacteria using Fosfomycin?

Fosfomycin for Treatment of ESBL-Producing Bacterial UTIs

Fosfomycin is highly effective for treating urinary tract infections caused by ESBL-producing bacteria, with high-certainty evidence supporting intravenous fosfomycin for complicated UTIs and oral fosfomycin as an effective single-dose treatment for uncomplicated UTIs. 1

Efficacy Against ESBL-Producing Organisms

• Fosfomycin demonstrates excellent in vitro activity against ESBL-producing Enterobacteriaceae:

  • 96.8% of ESBL-producing E. coli isolates are susceptible 2
  • 81.3% of ESBL-producing K. pneumoniae isolates are susceptible 2
  • 92% overall susceptibility in ESBL-producing Enterobacteriaceae 3

• Clinical success rates for ESBL-producing E. coli UTIs treated with oral fosfomycin:

  • 94.3% clinical success (symptom resolution) 4
  • 78.5% microbiological success (sterile urine culture) 4

Treatment Recommendations by UTI Type

Uncomplicated UTIs (Acute Cystitis)

• First-line therapy: Single 3g dose of oral fosfomycin trometamol 5
• Particularly effective for uncomplicated UTIs in women due to susceptible strains of E. coli and Enterococcus faecalis 6
• Administration: Single-dose sachet mixed with water, taken on an empty stomach

Complicated UTIs (With or Without Bacteremia)

• Intravenous fosfomycin: High-certainty evidence supports its use for complicated UTIs caused by ESBL-producing Enterobacteriaceae 1
• Comparable efficacy to carbapenems (meropenem) and piperacillin-tazobactam in clinical trials 1
• Caution: Monitor patients with heart failure risk (8.6% developed heart failure in the FOREST trial) 1

Dosing Considerations

• Uncomplicated UTIs: Single 3g oral dose 6
• Complicated UTIs: Extended regimen may be necessary (3g every other night for three doses has shown 94.3% clinical success) 4
• Renal Impairment: No dosage adjustment necessary for oral fosfomycin in patients with varying degrees of renal impairment 6
• Hemodialysis Patients: Administer after hemodialysis sessions to avoid premature removal of the drug 5

Advantages of Fosfomycin for ESBL Infections

1. Unique mechanism of action (inhibits enolpyruvyl transferase) with no cross-resistance to other antibiotic classes 6
2. Excellent urinary concentrations (mean 706 μg/mL within 2-4 hours after dosing) 6
3. Maintains urinary concentrations >100 μg/mL for 26 hours 6
4. Can be taken without regard to food (though peak concentrations are higher when fasting) 6
5. Cost-effective alternative to parenteral therapies for outpatient management 7

Important Caveats and Limitations

• Not indicated for pyelonephritis or perinephric abscess 6
• If bacteriuria persists or recurs after treatment, select alternative agents 6
• Resistance can develop during treatment in some cases, particularly with carbapenem-resistant Enterobacteriaceae 3
• Limited data on optimal dosing duration for complicated infections 7

Monitoring and Follow-up

• Assess clinical response within 48-72 hours
• Consider follow-up urine culture in complicated cases or treatment failures
• No routine post-treatment urinalysis or urine cultures needed for asymptomatic patients with resolved symptoms 5

Fosfomycin represents a valuable carbapenem-sparing option for treating UTIs caused by ESBL-producing bacteria, with strong evidence supporting its efficacy and safety profile, particularly for uncomplicated infections.