Description

Fosfomycin is a broad-spectrum antibiotic that belongs to a unique class of antibiotics, the phosphonic acid derivatives. Fosfomycin calcium is a specific salt form of the drug, often formulated for oral administration. It is a bactericidal agent, meaning it kills bacteria, and is effective against a wide range of both Gram-positive and Gram-negative bacteria.

Indications

The primary indication for Fosfomycin Calcium is the treatment of uncomplicated urinary tract infections (UTIs), specifically acute cystitis in adult women, caused by susceptible strains of Escherichia coli and Enterococcus faecalis. Due to its high concentration in the urinary tract, it is particularly well-suited for this purpose.

While fosfomycin has a broad spectrum of activity, its use in many regions is limited to uncomplicated UTIs. This is because other forms of fosfomycin (such as the tromethamine or disodium salts) are also available, and the different salts have varying pharmacokinetic properties, including bioavailability. Fosfomycin calcium is less bioavailable than the tromethamine salt, which may influence its use and dosing recommendations. It is not indicated for more complex infections like pyelonephritis or perinephric abscesses.

Mechanism of Action

Fosfomycin’s mechanism of action is unique and different from other common antibiotic classes, which contributes to its low rate of cross-resistance. It works by inhibiting a crucial early step in the synthesis of the bacterial cell wall.

1. Targeting MurA Enzyme: Fosfomycin is a structural analog of phosphoenolpyruvate (PEP). It works by irreversibly inhibiting the enzyme UDP-N-acetylglucosamine enolpyruvyl transferase, commonly known as MurA.

2. Irreversible Inhibition: The drug forms a covalent bond with a cysteine residue in the active site of the MurA enzyme, which permanently inactivates it.

3. Disruption of Cell Wall Synthesis: The MurA enzyme is responsible for catalyzing the first committed step in the synthesis of peptidoglycan, the primary structural component of the bacterial cell wall. By inhibiting MurA, fosfomycin prevents the formation of N-acetylmuramic acid, a vital precursor.

4. Cell Lysis: Without a properly formed peptidoglycan layer, the bacterial cell wall becomes weak and unstable. This makes the bacterium highly susceptible to osmotic pressure, leading to cell swelling and eventual rupture (lysis).

Fosfomycin enters bacterial cells through specific transport systems, primarily the L-alpha-glycerophosphate and hexose-6-phosphate transporter systems. This unique uptake mechanism and its early-stage inhibition of cell wall synthesis make it an effective agent against a wide variety of bacteria, including some that are multi-drug resistant.