Fosfomycin Classification
Fosfomycin is a phosphonic acid derivative antibiotic that acts by inhibiting bacterial cell wall synthesis through a unique mechanism of action. 1, 2
Mechanism of Action
Fosfomycin works through a distinctive mechanism:
- Inhibits the enzyme enolpyruvyl transferase (MurA)
- Blocks the initial step in bacterial cell wall synthesis by preventing the condensation of uridine diphosphate-N-acetylglucosamine with p-enolpyruvate 1
- This mechanism differs from other antibiotic classes, which explains its minimal cross-resistance with other antibiotics 2, 3
Antimicrobial Spectrum
Fosfomycin demonstrates broad-spectrum activity against:
- Gram-positive bacteria: Staphylococcus aureus, Enterococcus faecalis
- Gram-negative bacteria: Escherichia coli, Citrobacter, Enterobacter, Klebsiella, Serratia, and some strains of Pseudomonas aeruginosa 1, 2, 4
Clinical Applications
Fosfomycin is primarily used for:
- Uncomplicated urinary tract infections, particularly those caused by E. coli and E. faecalis 1, 5
- Potential use in combination therapy for multidrug-resistant bacterial infections 2, 6
- In Japan, fosfomycin has been studied for treatment of STEC (Shiga toxin-producing E. coli) infections 6
Formulations
Fosfomycin is available in three forms:
- Fosfomycin tromethamine (oral soluble salt)
- Fosfomycin calcium (oral)
- Fosfomycin disodium (intravenous) 2
Pharmacokinetic Properties
- Oral bioavailability: 34-41%
- Mean elimination half-life: 5.7 hours
- Primary excretion: unchanged in urine
- High urinary concentrations (>128 mg/L) maintained for 24-48 hours after a single 3g dose 1, 5
Resistance Mechanisms
Bacteria can develop resistance to fosfomycin through:
- Modification of the target enzyme (MurA)
- Reduced antibiotic uptake
- Enzymatic inactivation of the antibiotic 3
Clinical Considerations
- Fosfomycin has good tissue distribution, reaching clinically relevant concentrations in various tissues including kidneys, bladder wall, prostate, and lungs 2
- Well-tolerated with low incidence of adverse events, primarily mild gastrointestinal symptoms 5
- The unique mechanism of action makes it valuable for treating infections caused by multidrug-resistant pathogens 2, 4
Fosfomycin's distinctive phosphonic acid structure and mechanism of action make it stand apart from other antibiotic classes, providing an important option in the antimicrobial armamentarium, especially as resistance to other antibiotics increases.