Fosfomycin for E. coli Treatment
Fosfomycin is highly effective for uncomplicated urinary tract infections caused by E. coli, particularly as a single 3g oral dose, but is FDA-approved only for uncomplicated UTIs in women and should not be used for pyelonephritis or systemic infections. 1, 2
Indications and Efficacy
Urinary Tract Infections
- Fosfomycin is a first-line treatment for uncomplicated UTIs caused by susceptible strains of E. coli and Enterococcus faecalis 1, 2
- The American Urological Association and Infectious Diseases Society of America recommend fosfomycin as a preferred agent for uncomplicated UTIs 2
- Particularly valuable for ESBL-producing E. coli UTIs with clinical success rates >78% in multiple studies 3, 4
- Standard dosing: 3g single dose oral powder formulation 2, 1
Limitations
- Not indicated for pyelonephritis, perinephric abscess, or systemic infections 1
- Should not be used for persistent or recurrent UTIs without selecting alternative agents 1
- Not FDA-approved for male UTIs or complicated UTI scenarios 1
Resistance Considerations
Resistance Mechanisms
- Resistance rates remain relatively low but are increasing (6.7-10.9% in recent studies) 5, 6
- Primary mechanism of resistance is plasmid-mediated fosA genes (fosA3 most common) 5, 7, 6
- Secondary mechanisms include mutations in MurA and GlpT transport proteins 5
- Concerning trend of co-localization of fosA and ESBL genes (blaCTX-M) on the same transferable plasmids 5, 7, 6
Clinical Implications
- Resistance should be monitored as fosfomycin use increases globally 7
- Local resistance patterns should guide empiric therapy choices 2
- Consider susceptibility testing before use in areas with known high resistance rates 2
Treatment Recommendations
First-line Use
- For uncomplicated UTIs in women: Single 3g oral dose 2, 1
- For ESBL-producing E. coli UTIs: Consider extended regimen of 3g every other night for three doses (total 9g) 4
- Particularly valuable for outpatient management of community-acquired ESBL-producing E. coli UTIs 3
Combination Therapy
- For carbapenem-resistant Enterobacteriaceae (CRE) infections, fosfomycin may be used in combination with other agents 8
- Fosfomycin-containing combination therapy showed reduced mortality in CRE infections compared to other combinations (RR=0.55) 8
Contraindications
- Avoid in pyelonephritis or systemic infections 1
- Not recommended for E. coli causing diarrheal disease (STEC) as antibiotics may increase risk of hemolytic uremic syndrome 8
Monitoring and Follow-up
- Perform follow-up urine culture if symptoms persist after treatment 1
- If bacteriuria recurs after treatment, select alternative agents rather than repeating fosfomycin 1
- Monitor for hypokalemia in critically ill patients receiving IV formulations (not available in US) 8
Advantages
- Minimal resistance compared to other oral options
- Single-dose administration improves compliance
- Limited drug interactions and favorable safety profile
- Maintains activity against many multidrug-resistant strains
- Cost-effective alternative to parenteral therapy for resistant organisms 3
Fosfomycin represents an important treatment option for E. coli UTIs, especially in the era of increasing antimicrobial resistance. Its unique mechanism of action, convenient dosing, and efficacy against resistant strains make it particularly valuable, though careful stewardship is needed to preserve its utility.