Fosfomycin

Bladder Infections

Fosfomycin is most commonly prescribed to treat acute cystitis, which is a simple bladder infection. It belongs to a class of medications called antibiotics and works by stopping the growth of bacteria in the urinary tract.

This medication is specifically indicated for infections caused by certain susceptible bacteria, including:

• Escherichia coli (E. coli)
• Enterococcus faecalis

Other Applications

While the oral form is typically used for simple bladder infections, healthcare providers may use different formulations for other types of infections in specific clinical settings:

• Oral granules: These are usually taken as a single dose dissolved in water for uncomplicated infections.
• Intravenous (IV) use: In some cases, an injectable form may be used for more complex or serious infections, such as those affecting the bones, lungs, or blood, particularly when the bacteria are resistant to other antibiotics.

Fosfomycin is generally not used to treat more severe kidney infections, such as pyelonephritis or perinephric abscesses.

Mechanism of Action

Fosfomycin is a bactericidal antibiotic, which means it works by directly killing bacteria. It achieves this by disrupting the production of the bacterial cell wall, a structure that bacteria need to maintain their shape and survive.

The process involves several key steps:

• Enzyme Inhibition: Fosfomycin blocks a specific enzyme called MurA. This enzyme is responsible for the very first step in the synthesis of peptidoglycan, a vital component of the bacterial cell wall.
• Cell Wall Failure: By stopping this initial building block from being formed, the drug prevents the bacteria from completing their cell wall. Without a functional wall, the bacteria eventually burst and die.
• Cell Entry: To work, the drug must get inside the bacterial cell. It does this by using the bacteria's own transport systems, essentially tricking the cell into absorbing the medication.

Unique Chemical Structure

Fosfomycin is chemically unrelated to other common classes of antibiotics, such as penicillins, cephalosporins, or tetracyclines. Because it works at a different stage of cell wall production than most other drugs, it may remain effective against certain types of bacteria that have developed resistance to other antibiotic treatments.

Common Side Effects

The most frequently reported side effects of fosfomycin include:

• Diarrhea
• Nausea
• Headache
• Dizziness
• Stomach pain or indigestion
• Vaginal itching or discharge
• Back pain
• Weakness

Serious Side Effects

While less common, some side effects can be serious. Contact a healthcare provider immediately if you experience:

• Severe diarrhea that is watery or bloody, which may occur with or without stomach cramps and fever
• Signs of an allergic reaction, such as a skin rash, hives, or swelling of the face, lips, or tongue
• Difficulty breathing or wheezing
• Changes in vision
• Hearing loss or ringing in the ears

Severe diarrhea caused by a specific bacterial infection (Clostridioides difficile) can occur during treatment or even several months after the last dose. Do not use anti-diarrhea medications without consulting a doctor if you have watery or bloody stools.

Hypersensitivity Reactions

Serious and potentially life-threatening allergic reactions, including anaphylaxis, can occur with fosfomycin use. If signs of a severe allergic reaction appear, the medication should be stopped immediately and medical intervention sought.

Clostridioides difficile-Associated Diarrhea

Treatment with antibacterial agents can change the normal bacteria in the colon, leading to an overgrowth of Clostridioides difficile. This can cause diarrhea ranging from mild to fatal colitis. This condition may occur during treatment or several months after the medication is finished.

Development of Drug-Resistant Bacteria

Prescribing fosfomycin without a confirmed or strongly suspected bacterial infection is unlikely to provide benefit and increases the risk that bacteria will become resistant to the medication.

Sodium Monitoring

The intravenous formulation of this medication contains a high amount of sodium. Caution is necessary for patients with conditions that require sodium restriction, such as heart failure, liver disease, or kidney impairment, as it may lead to fluid overload or electrolyte imbalances.

Contraindications

• Fosfomycin is contraindicated in patients with a known hypersensitivity to the drug or any of its components.

Pregnancy

Animal studies have not demonstrated a risk to the fetus when fosfomycin is administered. However, there is a lack of well-controlled studies in pregnant humans. For this reason, healthcare providers generally only prescribe fosfomycin during pregnancy if the potential benefits justify the potential risks to the fetus.

Breastfeeding

It is currently unknown whether fosfomycin passes into human breast milk. Because many medications can be transferred through milk and may affect a nursing infant, caution is advised. Patients should discuss the risks and benefits of breastfeeding while taking this medication with their healthcare provider. Decisions often involve weighing the importance of the medication for the mother's health against the potential effects on the infant.

Available Forms

Fosfomycin is provided in the following form:

• Oral Granules: This medication comes as granules in a packet. It is designed to be dissolved in water and taken as an oral solution.

The granules must be mixed with cold water before use and should not be swallowed dry. This medication is usually taken as a one-time treatment.

FDA Approval Status

Fosfomycin tromethamine, the oral version of the medication, was first approved by the U.S. Food and Drug Administration (FDA) in 1996. In 2024, the FDA approved an intravenous formulation of fosfomycin for use in adult patients.

Approved Indications

The FDA has approved fosfomycin for the following specific uses:

• Oral granules: Treatment of uncomplicated urinary tract infections (acute cystitis) in women caused by susceptible strains of bacteria.
• Intravenous injection: Treatment of complicated urinary tract infections (cUTI), including pyelonephritis, in adults.

Safety and Regulatory Oversight

There are currently no boxed warnings associated with fosfomycin. A boxed warning is the FDA's most serious safety notification for medications. Additionally, there is no Risk Evaluation and Mitigation Strategy (REMS) required for this drug. Regulatory approval is maintained based on clinical evidence of the drug's safety and effectiveness for its indicated uses.

FDA-Approved Indications

The U.S. Food and Drug Administration (FDA) has approved fosfomycin tromethamine for the treatment of uncomplicated urinary tract infections (acute cystitis) in women. It is specifically indicated for infections caused by susceptible strains of the following bacteria:

• Escherichia coli
• Enterococcus faecalis

Fosfomycin is not indicated for the treatment of kidney infections, such as pyelonephritis or perinephric abscess.

Usage and Administration

The FDA-approved dosage form is oral granules that must be mixed with water before consumption. It is intended as a single-dose treatment. Clinical trials have shown that a single dose is effective for its approved use in women 18 years of age and older.

Safety and Regulatory Information

As with most antibacterial drugs, the FDA requires warnings regarding the risk of Clostridioides difficile-associated diarrhea (CDAD), which can range in severity from mild diarrhea to fatal colitis. The FDA also notes that fosfomycin should only be used to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria to maintain the effectiveness of the drug and reduce the development of drug-resistant bacteria.