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Fosfomycin – Antibiotic for Urinary Tract Infections

Fosfomycin is a broad-spectrum antibiotic primarily used to treat uncomplicated urinary tract infections. It works by inhibiting bacterial cell wall synthesis and is effective against many gram-positive and gram-negative pathogens.

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Things worth knowing about "Fosfomycin"

Fosfomycin is a broad-spectrum antibiotic primarily used to treat uncomplicated urinary tract infections. It works by inhibiting bacterial cell wall synthesis and is effective against many gram-positive and gram-negative pathogens.

What is Fosfomycin?

Fosfomycin is an antibiotic with a unique chemical structure belonging to the phosphonic acid class of antibacterial agents. It was originally isolated from the bacterium Streptomyces fradiae and is now produced synthetically. Fosfomycin is available as an oral granule formulation (fosfomycin trometamol) and as an intravenous solution (fosfomycin sodium). It is considered a well-tolerated reserve antibiotic, particularly valuable in the era of increasing antibiotic resistance.

Indications

Fosfomycin is indicated for:

Uncomplicated urinary tract infections (UTIs) – particularly acute cystitis in women; this is the most common use of the oral formulation
Complicated UTIs and pyelonephritis (kidney infection) using high-dose intravenous regimens
Infections caused by multidrug-resistant organisms, including Extended-Spectrum Beta-Lactamase (ESBL)-producing bacteria and vancomycin-resistant enterococci (VRE)
Combination therapy for serious infections caused by Pseudomonas aeruginosa or Staphylococcus aureus

Mechanism of Action

Fosfomycin inhibits the enzyme MurA (UDP-N-acetylglucosamine enolpyruvyl transferase), which catalyzes an early and essential step in bacterial cell wall biosynthesis. By blocking this enzyme, bacteria are unable to construct a stable cell wall, ultimately leading to cell death. This mechanism of action is entirely distinct from those of other antibiotic classes such as beta-lactams or fluoroquinolones, which is why fosfomycin can remain active against bacteria resistant to these agents.

Spectrum of Activity

Fosfomycin has broad-spectrum activity against:

Gram-positive organisms: Staphylococcus aureus (including MRSA in combination therapy), Enterococcus faecalis
Gram-negative organisms: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa (in combination)

Activity against Enterococcus faecium and some other pathogens is more limited.

Dosage and Administration

Oral Administration (Fosfomycin Trometamol)

For uncomplicated UTIs, a single oral dose of 3 g fosfomycin trometamol (equivalent to 2 g fosfomycin) is recommended. This single-dose regimen offers excellent patient compliance and has been shown to be as effective as longer antibiotic courses for this indication.

Intravenous Administration (Fosfomycin Sodium)

For severe or complicated infections, high doses of 12 to 24 g per day are administered intravenously, divided into multiple doses. The exact dosage depends on the severity of infection, renal function, and body weight of the patient.

Side Effects

Fosfomycin is generally well tolerated. Possible side effects include:

Gastrointestinal complaints such as nausea, diarrhea, and abdominal discomfort (especially with oral use)
Headache and dizziness
Increased sodium load with intravenous use (fosfomycin sodium contains significant amounts of sodium – caution in patients with heart failure or kidney disease)
Elevated liver enzyme levels (rare)
Allergic reactions (rare)

Resistance Development

Resistance to fosfomycin can develop relatively quickly during monotherapy due to the selection of spontaneous bacterial mutants. To prevent this, fosfomycin is almost always used in combination with other antibiotics for serious infections. Combination therapy also reduces the risk of treatment failure in multidrug-resistant pathogens.

Special Patient Groups

Pregnancy: Oral fosfomycin trometamol is considered relatively safe during pregnancy and is included in clinical guidelines as an option for uncomplicated UTIs. Use should always be discussed with a treating physician.
Renal impairment: Dose adjustment is necessary in patients with reduced kidney function, as fosfomycin is predominantly eliminated via the kidneys.
Children: Fosfomycin may be used in children under medical supervision, with dosing based on body weight.

References

European Medicines Agency (EMA): Assessment report on fosfomycin-containing medicinal products. EMA/CHMP/742927/2017.
Ribera A, Benavent E, Tubau F, et al. - Fosfomycin for the treatment of multidrug-resistant bacterial infections. Clin Microbiol Infect. 2015.
Gupta K, Hooton TM, Naber KG, et al. - International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women. Clin Infect Dis. 2011;52(5):e103-e120.

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