Fosfomycin is a broad-spectrum bactericidal antibiotic with a unique chemical structure and mechanism of action, classified as an epoxide antibiotic. It is primarily indicated for the treatment of uncomplicated urinary tract infections (UTIs) caused by susceptible strains of designated microorganisms. Unlike many other antibiotics, fosfomycin demonstrates activity against a wide range of Gram-positive and Gram-negative uropathogens, including some multidrug-resistant strains. Its distinctive properties make it a valuable therapeutic option in specific clinical scenarios, particularly for acute cystitis in non-pregnant women.

Features

• Chemically known as (1R,2S)-1,2-epoxypropylphosphonic acid.
• Available in oral formulation as fosfomycin tromethamine (monohydrate salt).
• Possesses a unique mechanism of action, irreversibly inhibiting the bacterial enzyme MurA (UDP-N-acetylglucosamine enolpyruvyl transferase), a critical early step in cell wall synthesis.
• Exhibits a broad spectrum of in vitro activity against common uropathogens like Escherichia coli, Enterococcus faecalis, and Citrobacter species.
• Characterized by a low molecular weight, facilitating high urinary concentration and excretion in active form.
• Demonstrates a low potential for cross-resistance with other antibiotic classes.

Benefits

• Single-Dose Efficacy: The primary regimen for uncomplicated UTIs is often a single, oral dose, promoting exceptional patient adherence and completion rates.
• Rapid Bactericidal Action: Its unique mechanism leads to swift bacterial killing at the site of infection, providing prompt symptomatic relief.
• Favorable Resistance Profile: Maintains activity against many uropathogens that have developed resistance to more commonly used antibiotics like fluoroquinolones and trimethoprim-sulfamethoxazole.
• Minimal Impact on Gut Flora: The single-dose regimen and poor oral bioavailability help minimize disruption to the natural intestinal microbiota, reducing the risk of secondary infections like Clostridioides difficile.
• High Urinary Concentration: Achieves concentrations in the urine far exceeding the minimum inhibitory concentration (MIC) for most susceptible pathogens for 2-4 days post-administration, ensuring prolonged antimicrobial effect.
• Established Safety Profile: Has been used clinically for decades with a well-documented and generally favorable safety and tolerability spectrum.

Common use

Fosfomycin tromethamine is officially indicated for the treatment of uncomplicated urinary tract infections (acute cystitis) in women due to susceptible strains of Escherichia coli and Enterococcus faecalis. It is not indicated for the treatment of pyelonephritis or perinephric abscess. Its use may be considered in cases where first-line agents are contraindicated or not tolerated, or for infections caused by organisms with known resistance to other antimicrobials. Off-label uses, based on in vitro susceptibility and clinical experience, can include treatment or prophylaxis for other UTIs and, in its intravenous form (not discussed in detail here), for more serious systemic infections.

Dosage and direction

For uncomplicated UTIs in adult women, the typical dose is a single 3-gram sachet of fosfomycin tromethamine oral powder.

• Administration: The contents of one sachet should be dissolved in ½ glass (3-4 ounces / 90-120 mL) of cold water. It should not be dissolved with hot water. Stir to dissolve and drink the entire solution immediately.
• Timing: To ensure optimal absorption and high urinary concentration, it is recommended to take the dose immediately after mixing, preferably on an empty stomach (at least 2 hours before or 2 hours after a meal).
• Re-administration: A second 3-gram dose may be considered for patients who do not show a clinical response within 2-3 days, though this is not the standard protocol for uncomplicated cases. Dosing for other indications or patient populations (e.g., men, children) is not well-established for the oral formulation and requires careful medical supervision.

Precautions

• Diarrhea: As with nearly all antibacterial agents, fosfomycin may cause diarrhea. Patients should be advised that it could be a sign of a secondary infection, including C. difficile-associated diarrhea (CDAD), which can range in severity.
• Preexisting Conditions: Use with caution in patients with severe renal impairment (creatinine clearance <10 mL/min), as the primary excretion route is renal. Dose adjustment may be necessary, though data is limited.
• Pregnancy and Lactation: Fosfomycin crosses the placental barrier and is excreted in breast milk. It should be used during pregnancy and lactation only if clearly needed and after a careful risk/benefit assessment by a physician, though some studies support its use.
• Asthma: The tromethamine salt component may be of concern in patients with a history of significant asthma, though this is rare.
• Drug Resistance: As with any antibiotic, unnecessary use or misuse can lead to the development of drug-resistant bacteria. Fosfomycin should be used only to treat infections proven or strongly suspected to be caused by susceptible bacteria.

Contraindications

Fosfomycin tromethamine is contraindicated in patients with a known history of hypersensitivity to fosfomycin or any of the excipients in the formulation.

Possible side effect

Most side effects are generally mild to moderate and transient. Common adverse reactions (>1%) may include:

• Diarrhea
• Nausea
• Headache
• Dizziness
• Vaginitis Less common side effects can include:
• Dyspepsia (indigestion)
• Abdominal pain
• Rash
• Rhinitis
• Back pain
• Asthenia (weakness) Serious side effects are rare but require immediate medical attention. These include severe diarrhea (potentially indicating pseudomembranous colitis), severe allergic reactions (e.g., anaphylaxis, angioedema), and exacerbation of asthma.

Drug interaction

Formal drug interaction studies are limited. However, theoretical and potential interactions include:

• Metoclopramide: Coadministration may lower serum and urinary concentrations of fosfomycin by accelerating gastric transit and reducing absorption. Concurrent use is not recommended.
• Other Oral Medications: Due to the cation content (tromethamine) and its effect on gastric pH and motility, fosfomycin may affect the absorption of other drugs taken orally. It is advisable to administer other oral medications at least 2 hours before or after fosfomycin.
• No significant interactions with cytochrome P450 enzymes are known.

Missed dose

Given that the standard regimen is a single dose, the concept of a “missed dose” primarily applies if a second dose has been prescribed. If a subsequent dose is missed, it should be taken as soon as it is remembered. However, if it is almost time for the next scheduled dose, the missed dose should be skipped, and the regular dosing schedule resumed. Patients should not double the dose to make up for a missed one.

Overdose

Experience with fosfomycin tromethamine overdose is limited. Given its safety profile, significant toxicity is not expected. High doses may lead to an increase in the frequency or severity of the reported adverse effects, particularly gastrointestinal events like diarrhea. Treatment of overdose should consist of general supportive measures, including maintaining hydration and electrolyte balance. Fosfomycin is removed by hemodialysis.

Storage

• Store the powder sachets at room temperature, between 20°C to 25°C (68°F to 77°F).
• Protect from excessive moisture.
• Keep the medication in its original packaging until ready to use.
• Keep all medicines out of the reach of children and pets.

Disclaimer

This information is for educational and informational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or before starting any new treatment. Never disregard professional medical advice or delay in seeking it because of something you have read here. The content provided reflects information available at the time of writing and may not encompass the most recent research, approvals, or guidelines.

Reviews

“Fosfomycin remains a crucial tool in our arsenal against uropathogens, especially in the era of rising antimicrobial resistance. Its single-dose convenience is unmatched for compliant outpatient management of acute cystitis.” – Infectious Disease Specialist “As a primary care physician, I value fosfomycin for patients who present with a UTI and have contraindications to first-line agents like sulfa drugs or nitrofurantoin. Its efficacy and safety profile are well-established.” – General Practitioner “From a microbiological perspective, fosfomycin’s unique mechanism means we see less cross-resistance. It’s an important antibiotic to preserve, so its use should be guided by susceptibility testing when possible.” – Clinical Microbiologist