Fosfomycin's Effectiveness Against E. coli and Proteus UTIs
Fosfomycin is highly effective against Escherichia coli and Proteus mirabilis in urinary tract infections, with excellent in vitro activity demonstrated against these common uropathogens. 1, 2
Antimicrobial Coverage
E. coli Coverage
- Fosfomycin demonstrates excellent activity against E. coli, with susceptibility rates of 99.6% in recent US studies 2
- FDA-approved specifically for uncomplicated UTIs due to susceptible strains of E. coli 1
- Maintains effectiveness against multidrug-resistant E. coli strains, including ESBL-producing isolates 3, 4
- Achieves high urinary concentrations (up to 706 μg/mL within 2-4 hours after a single dose) that far exceed the MICs for most E. coli strains 1
Proteus Coverage
- Shows good in vitro activity against Proteus mirabilis with MIC90 values indicating susceptibility 2, 5
- While not specifically FDA-approved for Proteus infections, clinical evidence supports its effectiveness 5
- The Infectious Diseases Society of America (IDSA) guidelines acknowledge fosfomycin's activity against resistant gram-negative rods, including Proteus species 6
Clinical Application
Dosing and Administration
- Standard dosing is a single 3g oral sachet for uncomplicated UTIs 7, 1
- Food may delay but does not reduce the total amount of drug excreted in urine 1
- Maintains urinary concentrations above 100 μg/mL for approximately 26 hours 1
Advantages
- Single-dose regimen improves patient compliance 6, 7
- Minimal impact on intestinal flora compared to other antibiotics 6
- Low resistance rates globally despite decades of use 6, 8
- Effective option for multidrug-resistant pathogens 3, 4
Limitations
- Lower bacterial eradication rates (80%) compared to some other first-line agents (>90%) 6
- Not indicated for pyelonephritis or perinephric abscess 1
- If bacteriuria persists or recurs after treatment, alternative agents should be selected 1
Resistance Considerations
- Primary mechanism of resistance is the fosA3 gene, but resistance remains relatively uncommon 4
- Resistance rates have remained stable over time in most regions 5
- In areas with high resistance to trimethoprim-sulfamethoxazole and fluoroquinolones, fosfomycin remains a valuable option 8
Practical Recommendations
- Consider fosfomycin as a first-line option for uncomplicated lower UTIs caused by E. coli 7
- For Proteus UTIs, fosfomycin is an effective option when susceptibility is confirmed 2, 5
- For pregnant patients with asymptomatic bacteriuria or lower UTIs, fosfomycin is a safe and effective single-dose option 5
- In cases of treatment failure, switch to an alternative agent based on susceptibility testing 1
Fosfomycin's unique mechanism of action, low resistance rates, and convenient single-dose administration make it a valuable option for treating uncomplicated UTIs caused by E. coli and Proteus species, particularly in an era of increasing antimicrobial resistance.