What is the best treatment for a urinary tract infection (UTI) that is not resolving with fosfomycin?

Treatment Options for UTIs Not Responding to Fosfomycin

For urinary tract infections that do not respond to fosfomycin treatment, nitrofurantoin (100mg twice daily for 5 days) is the recommended alternative first-line therapy due to its high efficacy and low resistance rates. 1, 2

First-Line Alternatives After Fosfomycin Failure

• Nitrofurantoin 100mg twice daily for 5 days is the most appropriate next option, with clinical efficacy rates of approximately 90% and microbiological efficacy of 93% 1, 2
• Trimethoprim-sulfamethoxazole 160/800mg twice daily for 3 days can be considered if local resistance rates are below 20% 1, 2
• Amoxicillin-clavulanate is recommended by the WHO Expert Committee as another first-choice option for lower UTIs 1

Treatment Algorithm Based on Patient Factors

For Uncomplicated UTIs in Women:

1. First option: Nitrofurantoin 100mg twice daily for 5 days 1, 2
2. Second option: Trimethoprim-sulfamethoxazole 160/800mg twice daily for 3 days (if local resistance <20%) 1, 2
3. Third option: Amoxicillin-clavulanate (dose varies by formulation) 1
4. Fourth option: Cephalosporins such as cefadroxilo 500mg twice daily for 3 days (if local E. coli resistance <20%) 3

For Complicated or Resistant Infections:

• Consider urine culture and susceptibility testing to guide therapy 2, 4
• For suspected multidrug-resistant pathogens, parenteral options may include:
  • Ceftriaxone or ciprofloxacin for acute pyelonephritis 1
  • Aminoglycosides for carbapenem-resistant Enterobacteriaceae 3, 4

Rationale for Treatment Selection

Nitrofurantoin is preferred as the next option after fosfomycin failure for several reasons:

• High microbiological efficacy (93%) compared to fosfomycin (80%) 1
• Maintains high activity against most uropathogens, including E. coli (85.5% susceptibility) 5
• Lower resistance rates compared to fluoroquinolones and trimethoprim-sulfamethoxazole 5
• Recommended by both IDSA and European guidelines as a first-line agent 2

Important Considerations

• The FDA label for fosfomycin explicitly states: "If persistence or reappearance of bacteriuria occurs after treatment with fosfomycin tromethamine granules for oral solution, other therapeutic agents should be selected" 6
• Fluoroquinolones should be avoided as routine treatment due to increasing resistance rates and potential for collateral damage 1, 3
• Beta-lactams (except pivmecillinam) generally have lower efficacy for UTIs compared to other antimicrobials 3
• Obtain urine culture before starting alternative therapy if the patient has:
  • Symptoms that persist or recur within 2-4 weeks after treatment 2
  • Risk factors for resistant organisms 4
  • Failed multiple antibiotic courses 2

Special Populations

• For men with UTIs, longer treatment durations are typically needed (7 days) with trimethoprim-sulfamethoxazole or fluoroquinolones based on susceptibility 3, 2
• For pregnant women, avoid trimethoprim-sulfamethoxazole in the first and last trimesters 3
• For patients with recurrent UTIs, consider prophylactic regimens after addressing the acute infection 3, 2

Emerging Evidence on Resistant Pathogens

• For multidrug-resistant UTIs, fosfomycin may still be effective against ESBL-producing organisms and VRE, but clinical data are limited 4, 7
• E. coli isolates show high susceptibility to fosfomycin (95.5%), nitrofurantoin (85.5%), and cefuroxime (82.3%) even in recurrent UTI settings 5
• Fosfomycin should not be used for asymptomatic bacteriuria except in specific circumstances 2, 8