Fosfomycin: Targeted Antibiotic Therapy for Urinary Tract Infections
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Synonyms | |||
Fosfomycin is a broad-spectrum bactericidal antibiotic with a unique chemical structure and mechanism of action, offering a valuable therapeutic option for uncomplicated urinary tract infections (UTIs). As a phosphonic acid derivative, it inhibits bacterial cell wall synthesis by targeting the enzyme MurA (UDP-N-acetylglucosamine enolpyruvyl transferase), a critical early step in peptidoglycan formation. Its favorable pharmacokinetic profile, including high urinary concentrations and minimal systemic absorption when administered orally, makes it particularly effective against common uropathogens. This agent is available in several formulations, with fosfomycin tromethamine being the most commonly used oral preparation for outpatient management.
Features
- Unique phosphonic acid antibiotic structure, chemically distinct from beta-lactams, aminoglycosides, and fluoroquinolones
- Bactericidal activity through irreversible inhibition of MurA, preventing N-acetylmuramic acid formation
- Broad-spectrum coverage against Gram-positive and Gram-negative uropathogens, including Escherichia coli, Enterococcus faecalis, and Citrobacter species
- Oral formulation (fosfomycin tromethamine) provides high urinary drug concentrations exceeding MICs for most susceptible pathogens
- Single-dose administration option for uncomplicated UTIs enhances compliance
- Low protein binding and primarily renal excretion
- Minimal systemic absorption with focused urinary tract distribution
- Stability against many common bacterial resistance mechanisms, including extended-spectrum beta-lactamases (ESBLs)
Benefits
- Effective single-dose regimen for acute cystitis reduces treatment duration and improves adherence
- Maintains activity against multidrug-resistant organisms, including some ESBL-producing Enterobacteriaceae
- Favorable safety profile with minimal systemic side effects due to limited absorption
- Low risk of Clostridium difficile infection compared to broader-spectrum antibiotics
- Suitable for patients with penicillin allergies due to distinct chemical structure
- Convenient administration without regard to meals simplifies patient instructions
Common use
Fosfomycin is primarily indicated for the treatment of uncomplicated urinary tract infections (acute cystitis) in women caused by susceptible strains of Escherichia coli and Enterococcus faaecium. It may also be used off-label for complicated UTIs when susceptibility testing confirms appropriate coverage, particularly in cases of multidrug-resistant organisms. Some clinical guidelines recommend fosfomycin as an alternative first-line agent when resistance to first-line treatments is suspected or confirmed. In certain healthcare settings, it serves as part of antimicrobial stewardship programs to preserve broader-spectrum agents.
Dosage and direction
Adults (uncomplicated UTI): 3 grams of fosfomycin tromethamine oral sachet dissolved in ½ glass of water (4 ounces/120 mL), administered as a single dose. The solution should be consumed immediately after preparation.
Special populations: No dosage adjustment required for elderly patients with normal renal function. For patients with creatinine clearance between 10-50 mL/min, consider extended dosing intervals. Not recommended for patients with creatinine clearance <10 mL/min.
Administration: Best administered at bedtime after emptying the bladder to maximize urinary concentration. May be taken with or without food, though administration on an empty stomach may enhance absorption.
Precautions
Use with caution in patients with renal impairment (creatinine clearance <50 mL/min). Monitor for superinfection or fungal overgrowth with prolonged use. Not recommended for treatment of pyelonephritis or perinephric abscess due to potentially inadequate tissue penetration. Use during pregnancy only if clearly needed (Category B). Exercise caution in diabetic patients due to potential for urinary glucose interference with certain testing methods. Not intended for prophylactic use or long-term therapy.
Contraindications
Known hypersensitivity to fosfomycin or any component of the formulation. Contraindicated in patients with severe renal impairment (creatinine clearance <10 mL/min). Not recommended for children under 12 years of age due to limited safety and efficacy data. Should not be used for systemic infections outside the urinary tract due to limited serum concentrations.
Possible side effect
Common (>1%): Diarrhea, nausea, headache, vaginitis, rhinitis Less common (0.1-1%): Abdominal pain, dizziness, dyspepsia, back pain Rare (<0.1%): Allergic reactions, eosinophilia, elevated liver enzymes, thrombocytopenia Post-marketing reports: Pseudomembranous colitis, angioedema, anaphylactic reactions (very rare)
Drug interaction
Metoclopramide: May decrease fosfomycin serum concentrations—avoid concomitant use Cimetidine: Potential decrease in urinary concentration of fosfomycin Probenecid: May reduce renal excretion and urinary concentrations Oral contraceptives: Theoretical potential for reduced efficacy, though clinical significance uncertain—consider backup contraception Antacids containing magnesium or aluminum: May decrease absorption—separate administration by at least 2 hours
Missed dose
As fosfomycin for UTI is typically administered as a single dose, missed dose scenarios are uncommon. If a patient fails to take the prescribed single dose, it should be taken as soon as remembered. However, if it is close to the time for other medications or if several days have passed, consult a healthcare provider for guidance. Do not double the dose.
Overdose
No specific antidote exists for fosfomycin overdose. Symptoms may include gastrointestinal distress (nausea, vomiting, diarrhea). Management should be supportive, including maintenance of hydration and electrolyte balance. Hemodialysis may remove fosfomycin due to its low molecular weight and limited protein binding, though clinical experience with overdose is limited. Contact poison control center for latest guidance.
Storage
Store at room temperature (15-30°C/59-86°F) in original packaging. Protect from moisture and light. Keep the sachet sealed until ready for use. Once mixed with water, the solution should be used immediately and not stored. Keep out of reach of children and pets. Do not use after expiration date printed on packaging.
Disclaimer
This information is for educational purposes only and does not constitute medical advice. Fosfomycin is a prescription medication that should be used only under the supervision of a qualified healthcare professional. Healthcare providers should base treatment decisions on individual patient factors, local resistance patterns, and current clinical guidelines. Always consult appropriate prescribing information and clinical resources before administering any medication.
Reviews
“Fosfomycin has become an essential tool in our antimicrobial stewardship program. Its targeted spectrum and single-dose regimen make it ideal for appropriate outpatient UTI management while preserving broader agents.” - Infectious Disease Specialist, Academic Medical Center
“In my gynecology practice, fosfomycin has proven valuable for treating uncomplicated UTIs in young women, particularly those with recurrent infections or concerns about compliance with multi-day regimens.” - Gynecologist, Private Practice
“While fosfomycin shows excellent activity against many uropathogens, appropriate patient selection remains crucial. We reserve it for confirmed susceptible infections to prevent resistance development.” - Clinical Pharmacist, Hospital Setting