How is fosfomycin used to treat bacterial infections?

Fosfomycin Usage in Bacterial Infections

Fosfomycin should be used primarily for uncomplicated urinary tract infections as a single 3-gram oral dose, while intravenous fosfomycin can be considered as part of combination therapy for multidrug-resistant infections when susceptibility is confirmed. 1, 2

Oral Fosfomycin Administration

Indications

• Primary indication: Uncomplicated urinary tract infections (acute cystitis) in women due to susceptible strains of E. coli and Enterococcus faecalis 2
• Recommended as an excellent alternative for single-dose treatment of uncomplicated UTIs 1
• Particularly valuable for infections caused by multidrug-resistant organisms 1

Dosing

• Standard dose: 3 grams as a single oral dose 2
• Can be taken with or without food (although food may delay peak urinary concentration) 2
• Achieves high urinary concentrations (>100 μg/mL) for approximately 26 hours 2

Limitations

• Not indicated for pyelonephritis or perinephric abscess 2
• Lower clinical success rate (77%) compared to some alternatives (e.g., 98% for ciprofloxacin) 1
• Oral bioavailability is <50%, limiting its use for systemic infections 3

Intravenous Fosfomycin Administration

Indications

• Recommended for: Complicated infections caused by carbapenem-resistant gram-negative bacilli (CRE) when susceptibility is confirmed 4
• Particularly useful as part of combination therapy for multidrug-resistant infections 4, 5
• Potential applications in various infection sites including:
  • Pneumonia (41% of cases in clinical practice) 5
  • Bloodstream infections (19.6%) 5
  • Bone infections (16.1%) 5
  • Surgical site infections (7.1%) 5

Administration

• Always use in combination with other antibiotics (most commonly meropenem or colistin) 5
• Typical duration: Median of 10 days for complicated infections 5
• Requires confirmation of pathogen susceptibility through antimicrobial susceptibility testing before initiation 4

Monitoring Requirements

• Electrolyte monitoring is crucial during IV therapy due to significant imbalances:
  • Decreased serum potassium (average 0.6 mEq/L reduction)
  • Decreased calcium (average 0.7 mEq/L reduction)
  • Decreased magnesium (average 0.3 mg/dL reduction)
  • Increased sodium (average 4 mEq/L increase) 5
• More pronounced electrolyte changes in patients with kidney dysfunction or heart failure 5
• Consider diluting with 5% glucose solution rather than saline to minimize electrolyte imbalances 5

Special Considerations

Contraindications

• Avoid in patients with:
  • Hypernatremia
  • Cardiac insufficiency
  • Renal insufficiency 4

Antimicrobial Resistance

• Fosfomycin has preserved activity against many multidrug-resistant organisms 5
• FosA-like genes may cause fosfomycin resistance in some carbapenem-resistant Klebsiella pneumoniae 4
• Resistance rates vary (39-99% susceptibility in CRKP) 4
• Generally no cross-resistance with other antibiotic classes like beta-lactams and aminoglycosides 2

Mechanism of Action

• Bactericidal through irreversible inhibition of enolpyruvyl transferase, blocking bacterial cell wall synthesis 2
• Reduces bacterial adherence to uroepithelial cells 2
• Novel mechanism makes it valuable against resistant organisms 6

Clinical Efficacy

Urinary Tract Infections

• Complete resolution achieved in 39% of complicated infections when used in combination therapy 5
• For uncomplicated UTIs, recommended as first-line alternative to nitrofurantoin 1

Other Infections

• When used as part of combination therapy for various infections (including respiratory, bone, CNS), cure rates of approximately 81% have been reported 7
• Shows synergistic effects when combined with other antimicrobials acting via different mechanisms 3

Important Caveats

• Avoid monotherapy to prevent resistance development 3
• Do not use for STEC infections (Shiga toxin-producing E. coli) as antibiotics may increase risk of hemolytic uremic syndrome 4
• Always confirm susceptibility before initiating therapy for resistant organisms 4
• Monitor electrolytes closely, especially in patients with renal dysfunction or heart failure 5

Fosfomycin's unique mechanism of action, broad spectrum of activity, and efficacy against multidrug-resistant pathogens make it a valuable option in the antimicrobial armamentarium, particularly in this era of increasing antibiotic resistance.