Fosfomycin Sodium

Fosfomycin Sodium is a broad-spectrum bactericidal antibiotic used for the treatment of a variety of bacterial infections.

Approved Indications:

• Urinary Tract Infections (UTIs):
• Acute uncomplicated cystitis in adult women caused by Escherichia coli or Enterococcus faecalis.
• Complicated UTIs, including catheter-associated infections, in adults when oral therapy is not feasible.
• Prophylaxis:
• Perioperative prophylaxis in urologic procedures to prevent infection.
• Systemic Infections:
• Treatment of severe infections (e.g., bacteremia, endocarditis) caused by susceptible Gram-positive and Gram-negative bacteria, often in combination therapy.

Off-label / Clinically Accepted Uses:

• Osteomyelitis caused by susceptible bacteria.
• Respiratory tract infections, including pneumonia, particularly in multi-drug-resistant strains.
• Gastrointestinal infections caused by susceptible organisms, including Salmonella spp. and Shigella spp.
• Neonatal infections when standard therapies are contraindicated.

Adults:

• Uncomplicated UTIs: Single dose of 3 g orally, dissolved in water.
• Complicated UTIs or systemic infections: 4 g IV every 6–8 hours, adjusted based on severity.

Pediatrics:

• Oral: 50 mg/kg once daily for uncomplicated UTIs.
• IV: 100–200 mg/kg/day divided every 8 hours, based on severity and weight.

Special Populations:

• Elderly: Dose adjustment not generally required; monitor renal function.
• Renal impairment: Dose adjustment required based on creatinine clearance; reduce frequency in severe impairment.
• Hepatic impairment: No dose adjustment required.

Administration Route:

• Oral (powder solution) or intravenous infusion.
• Oral solution should be fully dissolved in water prior to ingestion.
• IV infusion typically over 30–60 minutes; monitor for thrombophlebitis.

Fosfomycin Sodium inhibits bacterial cell wall synthesis by irreversibly inactivating the enzyme UDP-N-acetylglucosamine enolpyruvyl transferase (MurA). This enzyme catalyzes the first step in peptidoglycan synthesis, essential for bacterial cell wall formation. Inhibition results in bactericidal activity against both Gram-positive and Gram-negative bacteria. Fosfomycin enters bacterial cells through glycerophosphate and hexose-6-phosphate transport systems, ensuring effective intracellular concentrations.

• Absorption: Oral bioavailability approximately 30–40%; peak plasma concentrations 2–2.5 hours post-dose.
• Distribution: Widely distributed; crosses bladder wall, kidneys, prostate, and bone tissue; protein binding <5%.
• Metabolism: Minimal hepatic metabolism.
• Half-life: 3–5 hours in healthy adults; prolonged in renal impairment.
• Excretion: Primarily excreted unchanged in urine (~90% within 24 hours); minor fecal excretion.
• Onset of action: Rapid bactericidal effect within hours after therapeutic dosing.

• Pregnancy: Limited human data; animal studies show no teratogenic effects. May be used if benefits outweigh risks (Pregnancy Category B).
• Lactation: Excreted in breast milk in small amounts; caution advised. Monitor infants for gastrointestinal disturbances.

• Primary Class: Antibiotic
• Subclass: Phosphonic acid derivative; bactericidal cell wall synthesis inhibitor

• Known hypersensitivity to fosfomycin or any excipients.
• History of severe allergic reactions to other antibiotics may warrant caution.
• Oral form contraindicated in patients with severe renal impairment without adjustment.
• IV form contraindicated in patients with anuria or severe renal failure without monitoring.

• Renal impairment: Monitor renal function and adjust dosing as needed.
• Electrolyte imbalance: Rare cases of hypokalemia or hypernatremia; monitor electrolytes during prolonged therapy.
• Gastrointestinal disturbances: Diarrhea may indicate Clostridioides difficile-associated diarrhea; discontinue if severe.
• Hypersensitivity reactions: Rare anaphylaxis; discontinue immediately if it occurs.
• Injection-site reactions: Pain, phlebitis, or thrombophlebitis with IV administration.

Common:

• Gastrointestinal: Diarrhea, nausea, vomiting, abdominal pain.
• Local reactions: Injection-site pain, phlebitis.

Serious / Rare:

• Hypersensitivity reactions including rash, urticaria, angioedema, anaphylaxis.
• Electrolyte disturbances (rare): Hypokalemia, hypernatremia.
• Pseudomembranous colitis (rare but serious).

Timing & Severity:

• GI effects may appear within hours of dosing; severity generally mild.
• Hypersensitivity reactions can occur after first dose.

• Other nephrotoxic drugs: May increase risk of renal impairment; monitor renal function.
• Warfarin: Limited interaction; monitor coagulation parameters when used concurrently.
• Antacids or oral iron supplements: May reduce oral absorption if taken simultaneously; separate dosing by at least 2–3 hours.
• Live bacterial vaccines: Potentially reduced efficacy if administered concomitantly during therapy.

• Recommended as a first-line oral therapy for uncomplicated UTIs in adult women due to low resistance and single-dose efficacy.
• Increasingly used in combination therapy for multidrug-resistant infections, including ESBL-producing E. coli.
• IV formulations emphasized for systemic and complicated infections in hospitalized patients.
• Updated guidelines stress renal function monitoring and caution in prolonged therapy.

• Store at 20°C to 25°C (room temperature).
• Protect from moisture and light; do not freeze.
• Oral powder: Keep in original container until use; dissolve completely before ingestion.
• IV solution: Store reconstituted solution at 2°C–8°C and use within recommended time frame; discard unused portions.