Is fosfomycin (antibiotic) effective against Proteus mirabilis in urinary tract infections (UTIs)?

Fosfomycin for Proteus mirabilis UTI

Yes, fosfomycin is effective against Proteus mirabilis in urinary tract infections. According to the FDA drug label, fosfomycin demonstrates in vitro activity against Proteus mirabilis with MICs of 64 mcg/mL or less against most (≥90%) strains 1.

Evidence Supporting Fosfomycin's Effectiveness Against P. mirabilis

FDA Approval and Drug Information

• The FDA drug label specifically lists Proteus mirabilis among the organisms against which fosfomycin demonstrates in vitro activity 1
• Fosfomycin works by inactivating the enzyme enolpyruvyl transferase, blocking bacterial cell wall synthesis 1
• It also reduces bacterial adherence to uroepithelial cells, providing an additional mechanism of action 1

Clinical Guidelines

• The European Association of Urology (2024) mentions that fosfomycin trometamol is recommended as a treatment option for asymptomatic bacteriuria in pregnant women 2
• Fosfomycin is listed as a first-line treatment option for uncomplicated UTIs according to the Praxis Medical Insights summary of clinical guidelines (2025) 3
• The recommended dosage for uncomplicated UTIs is a single 3g dose 3

Research Evidence on Susceptibility

• Research studies have demonstrated good in vitro activity of fosfomycin against Proteus mirabilis:
  • A 2015 study found that most urinary isolates were susceptible to fosfomycin, though it identified one resistant P. mirabilis isolate 4
  • A 2017 study reported high susceptibility rates among UTI isolates, including Proteus species 5
  • Another study from 2010 found that all tested Proteus mirabilis isolates were susceptible to fosfomycin 6

Clinical Considerations

Advantages of Fosfomycin

• Single-dose treatment improves compliance
• Achieves high urinary concentrations (706 ± 466 mcg/mL within 2-4 hours after administration) 1
• Maintains urinary concentrations ≥100 mcg/mL for approximately 26 hours 1
• Can be taken without regard to food 1

Important Caveats

1. Resistance Monitoring: While generally effective, isolated cases of fosfomycin-resistant P. mirabilis have been reported 4
2. Special Populations:
   • No dosage adjustment is necessary for elderly patients 1
   • In patients with renal impairment, fosfomycin half-life increases and urinary excretion decreases 1
3. Persistent Proteus Infections: If persistent growth of urease-producing bacteria like P. mirabilis is detected, stone formation in the urinary tract must be excluded 2

Treatment Algorithm for P. mirabilis UTI

1. For uncomplicated UTI: Single 3g dose of fosfomycin trometamol 3
2. For complicated or MDR UTI: Consider multiple doses of fosfomycin (evidence suggests effectiveness in these scenarios) 7
3. For persistent infection:
   • Evaluate for urinary stones (common with Proteus infections due to urease production) 2
   • Consider alternative antibiotics based on susceptibility testing
4. Follow-up: If symptoms persist after treatment, obtain follow-up urine culture and select an alternative agent rather than repeating fosfomycin 3

Fosfomycin represents an effective oral option for treating P. mirabilis UTIs, particularly valuable in the era of increasing antimicrobial resistance.