Fosfomycin tromethamine is a broad-spectrum bactericidal antibiotic indicated for the treatment of uncomplicated urinary tract infections (UTIs) in women. It exerts its effect by irreversibly inhibiting the early stages of bacterial cell wall synthesis, leading to cell death. Its unique pharmacokinetic profile allows for high concentrations in the urine for 24 to 48 hours following a single oral dose, making it a convenient and effective first-line option. This agent demonstrates in vitro activity against a wide range of Gram-positive and Gram-negative uropathogens, including many multidrug-resistant strains.

Features

• Active Ingredient: Fosfomycin tromethamine.
• Pharmacologic Class: Epoxy phosphonic acid antibiotic; synthetic, broad-spectrum bactericidal agent.
• Mechanism of Action: Irreversibly inhibits the enzyme MurA (UDP-N-acetylglucosamine enolpyruvyl transferase), a critical catalyst in the first committed step of bacterial cell wall (peptidoglycan) synthesis.
• Spectrum of Activity: Effective against common uropathogens such as Escherichia coli, Enterococcus faecalis, and Citrobacter species. Also shows activity against some extended-spectrum beta-lactamase (ESBL)-producing and methicillin-resistant Staphylococcus aureus (MRSA) isolates.
• Administration: Oral, single-dose sachet formulation for reconstitution.
• Bioavailability: Approximately 34% to 41% under fasting conditions; significantly enhanced when taken with food.

Benefits

• Single-Dose Convenience: A complete course of therapy is administered in one dose, significantly improving patient adherence and compliance compared to multi-day regimens.
• Rapid Bactericidal Action: Achieves high urinary concentrations quickly, providing effective and prompt eradication of susceptible pathogens at the site of infection.
• Low Resistance Potential: Its unique mechanism of action is distinct from other antibiotic classes, resulting in a low incidence of cross-resistance and making it a valuable option in an era of increasing antimicrobial resistance.
• Favorable Safety Profile: Generally well-tolerated with a low incidence of serious adverse events, making it suitable for a broad patient population.
• Minimal Impact on Gut Microbiome: The single-dose nature and poor systemic absorption limit disruption to the natural intestinal flora, potentially reducing the risk of secondary infections like Clostridioides difficile.

Common use

Fosfomycin tromethamine is primarily indicated for the treatment of uncomplicated urinary tract infections (acute cystitis) in women caused by susceptible strains of Escherichia coli and Enterococcus faecalis. It may also be considered for use in uncomplicated UTIs caused by other identified susceptible organisms based on culture and sensitivity results. Its role is typically as a first-line agent, especially in cases where patient compliance with a multi-day regimen is a concern or for infections with known or suspected resistance to other first-line antibiotics like trimethoprim-sulfamethoxazole.

Dosage and direction

• Standard Adult Dose (Women): A single 3-gram sachet dissolved in ½ glass (approximately 4 ounces) of cold water. Do not use hot water.
• Administration: Stir to dissolve and ingest the entire solution immediately. It is not intended to be stored for later use.
• Timing: To maximize absorption and urinary concentration, it should be taken immediately following a meal, preferably in the evening after emptying the bladder. This timing allows the drug to act in the bladder overnight.
• Renal Impairment: Dosage adjustment is not typically required for a single dose in mild to moderate impairment. Use with caution in patients with severe renal impairment (creatinine clearance <10 mL/min).
• Hepatic Impairment: No specific dosage adjustment is recommended.

Precautions

• Pregnancy: Fosfomycin crosses the placental barrier. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. Animal studies have not shown direct fetal harm, but adequate and well-controlled studies in pregnant women are lacking.
• Lactation: Fosfomycin is excreted in human milk. Caution should be exercised when fosfomycin is administered to a nursing woman.
• Diarrhea: Clostridioides difficile-associated diarrhea (CDAD) has been reported with nearly all antibacterial agents, including fosfomycin, and can range in severity from mild diarrhea to fatal colitis. Evaluate if diarrhea occurs.
• Asthma: Use with caution in patients with a history of asthma due to a potential for hypersensitivity reactions.
• Renal Function: Although a single dose is used, monitor patients with severe renal impairment for efficacy and potential side effects.

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 mild to moderate and transient. Common adverse reactions (≥1%) include:

• Diarrhea (9.0%)
• Vaginitis (5.9%)
• Nausea (4.1%)
• Headache (3.9%)
• Dizziness (1.3%)
• Dyspepsia (1.1%) Less common side effects include rhinitis, pharyngitis, back pain, and rash. As with all antibiotics, severe allergic reactions, though rare, are possible.

Drug interaction

• Metoclopramide: Concomitant use may lower the serum and urinary concentrations of fosfomycin, potentially reducing its efficacy. Avoid concurrent administration.
• Cimetidine: Cimetidine may reduce the urinary excretion of fosfomycin. The clinical significance of this interaction is unknown.
• Other Drugs that Increase GI Motility: Drugs that accelerate gastric emptying may similarly reduce fosfomycin absorption and should be used with caution.

Missed dose

As fosfomycin is administered as a single dose, the concept of a “missed dose” does not apply. The therapy is complete upon ingestion of the single sachet. If the dose is vomited shortly after administration, consult a healthcare provider for guidance on whether a repeat dose is necessary.

Overdose

Experience with overdose is limited. Given its pharmacokinetics, systemic toxicity from a single overdose is unlikely. High doses may exacerbate the reported adverse effects, particularly gastrointestinal events like diarrhea and nausea. Treatment should be supportive and symptomatic. Fosfomycin is removed by hemodialysis.

Storage

• Store the sealed sachet at controlled room temperature, 20°-25°C (68°-77°F).
• Protect from excessive moisture.
• Once mixed with water, the solution is for immediate use and should not be stored.

Disclaimer

This information is for educational and informational purposes only and does not constitute medical advice. It 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.

Reviews

• “As an infectious disease specialist, fosfomycin is a critical tool in our arsenal against multidrug-resistant UTIs. The single-dose regimen is a game-changer for patient compliance.” – Dr. A. Reynolds, MD
• “Clinical trial data consistently shows high microbiological eradication rates for susceptible E. coli, making it a reliable empiric choice.” – Clinical Pharmacologist Review
• “From a patient perspective, the convenience of a one-time treatment that effectively resolves symptoms within a day or two is highly valued and reduces the burden of illness.” – Summary of Patient Feedback Surveys