Is fosfomycin an appropriate antibiotic for lactose-fermenting gram-negative rods, including E. coli (Escherichia coli)?

Fosfomycin for Lactose-Fermenting Gram-Negative Rods Including E. coli

Yes, fosfomycin is appropriate for uncomplicated urinary tract infections (acute cystitis) caused by E. coli in women, but it is NOT appropriate for complicated UTIs, pyelonephritis, or systemic infections caused by these organisms. 1

FDA-Approved Indication

The FDA explicitly restricts oral fosfomycin to uncomplicated urinary tract infections (acute cystitis) in women caused by susceptible strains of Escherichia coli and Enterococcus faecalis. 1

• Fosfomycin is NOT indicated for pyelonephritis or perinephric abscess 1
• If bacteriuria persists or reappears after fosfomycin treatment, alternative agents must be selected 1

Clinical Efficacy Against E. coli

For Uncomplicated Cystitis

• Fosfomycin demonstrates excellent activity against E. coli with MIC90 ≤16 μg/ml 2
• A single 3-gram oral dose achieves therapeutic urinary concentrations for 24-48 hours 3
• The cumulative fraction of response is 99% against E. coli when urine pH is acidic (6.0) 2
• Fosfomycin remains active against ESBL-producing E. coli causing uncomplicated lower UTI 4, 3

Limitations in Bacterial Efficacy

• The bacterial eradication rate of fosfomycin is lower than other first-line agents for uncomplicated cystitis, though clinical efficacy is comparable 4
• Unpublished data referenced in IDSA guidelines demonstrate lower bacterial eradication rates compared to 10 days of trimethoprim-sulfamethoxazole and 7 days of ciprofloxacin 4

When Fosfomycin Should NOT Be Used

Complicated UTIs and Systemic Infections

• The European Association of Urology restricts fosfomycin to uncomplicated cystitis only, specifically excluding complicated UTIs and pyelonephritis 3
• Do not use oral fosfomycin for any complicated infection—it lacks sufficient data and has poor efficacy 3

Resistance Concerns

• Widespread chromosomal fosA genes are present in many Gram-negative species (Klebsiella, Enterobacter, Serratia, Pseudomonas) and confer intrinsic high-level fosfomycin resistance 5
• Plasmid-mediated fosfomycin resistance (fosA3, fosA4, fosA8) is increasingly common in E. coli, with all tested isolates showing MICs of 64 to >256 mg/L 6
• These resistance plasmids are conjugative and often co-carry ESBL or carbapenemase genes 6

Role in Multidrug-Resistant E. coli

Uncomplicated UTI Only

• Fosfomycin is an excellent choice for uncomplicated cystitis caused by ESBL-producing E. coli 3
• Oral fosfomycin monotherapy may be curative for uncomplicated UTI caused by MDR E. coli 7
• Pharmacokinetic/pharmacodynamic modeling suggests fosfomycin is effective against MDR E. coli in uncomplicated UTIs 8

Intravenous Fosfomycin for Severe Infections

• Intravenous fosfomycin has been used in combination therapy (not monotherapy) for carbapenem-resistant Enterobacteriaceae infections 4
• Fosfomycin-containing combinations may reduce mortality in MDR Gram-negative infections, though evidence quality is very low 4
• Monotherapy should be avoided due to high risk of resistance development 9

Critical Pitfalls to Avoid

• Do not use fosfomycin for pyelonephritis or complicated UTI—this violates FDA labeling and guideline recommendations 1, 3
• Do not use as monotherapy for systemic infections—combination therapy is required for serious infections 9
• Verify susceptibility testing before use—fosfomycin susceptibility is not routinely performed in many laboratories 4
• Avoid in patients with hypernatremia, cardiac, or renal insufficiency due to high sodium content of fosfomycin formulations 4

Advantages for Antibiotic Stewardship

• Single-dose regimen improves compliance 4
• Minimal collateral damage to intestinal flora 4, 9
• High E. coli susceptibility rates persist in regions with frequent fosfomycin use 4
• Carbapenem-sparing option in settings with high ESBL prevalence 4