What are the recommended fosfomycin dosing regimens for adults (oral for uncomplicated urinary tract infection), children, intravenous therapy, and how should the dose be adjusted in renal impairment and pregnancy?

Fosfomycin Dosing for Urinary Tract Infections

Standard Adult Oral Dosing for Uncomplicated Cystitis

For uncomplicated cystitis in adult women, administer fosfomycin trometamol 3 grams as a single oral dose, which provides therapeutic urinary concentrations for 24–48 hours and achieves approximately 91% clinical cure rates. 1, 2

Key Dosing Parameters

• Single-dose regimen: 3 grams orally once 1, 2
• Duration of urinary activity: Maintains therapeutic concentrations for 24–48 hours 2
• Clinical efficacy: 88.9–91% clinical cure rate 1, 3
• Microbiological eradication: 78–83% bacteriological cure 1

When to Use Fosfomycin

• First-line indication: Uncomplicated cystitis in women when trimethoprim-sulfamethoxazole resistance exceeds 20% in the community 2
• Multidrug-resistant pathogens: Excellent choice for ESBL-producing E. coli, vancomycin-resistant Enterococcus (VRE), and MRSA causing uncomplicated lower UTI 2
• Pregnancy: Safe for asymptomatic bacteriuria in pregnant women using the same single 3-gram dose 2, 4

Pediatric Dosing

For children ≥12 years: 3 grams (3000 mg) orally as a single dose 1

For children <12 years: 2 grams (2000 mg) orally as a single dose 1

Important Pediatric Considerations

• No recommendations are available for neonates or infants 1
• The pediatric formulation is restricted to oral use only 1
• Fosfomycin is not recommended for complicated UTIs or pyelonephritis in children 1

Intravenous Dosing (Where Available)

For multidrug-resistant organisms requiring IV therapy: 12–24 grams per day divided into 3 or 4 doses 1

IV Administration Details

• Standard regimen: 4–8 grams every 8 hours 1
• Infusion method: Administer as a 4-hour infusion to optimize pharmacokinetic/pharmacodynamic properties 1
• Always use in combination therapy for serious infections—never as monotherapy 1

Critical IV Limitations

• IV fosfomycin is not available in the United States 2
• IV formulation is restricted to complicated infections with carbapenem-resistant organisms in countries where it is available 2
• Oral fosfomycin should never be used for pyelonephritis or complicated UTIs 2, 5

Renal Impairment Dosing

For eGFR ≥30 mL/min/1.73 m²: No dose adjustment required; use standard 3-gram single dose 2

For eGFR <30 mL/min/1.73 m²: Fosfomycin can still be used at standard dosing, but monitor electrolytes closely 2

Renal Function Considerations

• The elimination half-life increases from 5.7 hours to 40–50 hours in anuric patients 2
• Patients with severe renal insufficiency, hypernatremia, or cardiac insufficiency should use fosfomycin with caution, particularly the IV formulation 2
• Monitor potassium, calcium, magnesium, and sodium during and after treatment in patients with pre-existing renal dysfunction 2

Multi-Dose Regimens (Off-Label)

For recurrent UTI or treatment failures: Fosfomycin 3 grams on days 1,3, and 5 (total of 3 doses over 5 days) 2

Evidence for Multi-Dose Regimens

• Pharmacokinetic modeling demonstrates that two 3-gram doses administered 72 hours apart maintain urinary concentrations above the critical threshold for 161 hours (66% efficacy time over 7 days) 6
• For systemic infections (not approved), 6–12 grams per day divided into 3 doses may be required to achieve efficacious serum concentrations 7
• Important caveat: Multi-dose oral regimens are not FDA-approved and lack robust clinical trial data 2

Absolute Contraindications

Do NOT use fosfomycin for:

• Pyelonephritis or upper urinary tract infections (insufficient efficacy data and poor tissue penetration) 1, 2, 5
• Complicated UTIs (including catheter-associated UTI, UTI in men, or UTI with anatomic abnormalities) 2, 5
• Non-fermenting gram-negative rods (e.g., Pseudomonas, Acinetobacter) 5
• Systemic infections outside the urinary tract (oral formulation does not achieve adequate serum concentrations) 7

Treatment Failure Management

If symptoms persist after 2–3 days or recur within 2 weeks:

• Obtain urine culture and susceptibility testing immediately 1, 2
• Switch to a different antibiotic class for a 7-day course (not another short regimen) 1, 2
• Consider nitrofurantoin 100 mg twice daily for 5 days, trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days (if susceptible), or a fluoroquinolone for 3 days 2

Common Pitfalls to Avoid

• Never use fosfomycin for febrile UTI or suspected pyelonephritis—switch to a fluoroquinolone or parenteral cephalosporin 1, 2
• Do not prescribe multiple doses empirically—the single 3-gram dose is the only FDA-approved regimen for uncomplicated cystitis 2, 4
• Avoid in patients with hypernatremia or severe cardiac insufficiency when using IV formulation 2
• Do not obtain routine post-treatment urine cultures in asymptomatic patients—only culture if symptoms persist or recur 1, 2

Comparative Efficacy

Fosfomycin vs. other first-line agents:

• Nitrofurantoin: Comparable clinical efficacy (91% vs. 93%), but fosfomycin has slightly lower microbiological cure (78–83% vs. 88%) 1, 8
• Trimethoprim-sulfamethoxazole: Comparable clinical efficacy (91% vs. 93%), but fosfomycin has lower microbiological cure (78–83% vs. 94%) 1
• Fluoroquinolones: Comparable clinical efficacy (91% vs. 90%), but fosfomycin offers single-dose convenience and minimal collateral damage to intestinal flora 1, 2

Advantages of Fosfomycin

• Single-dose convenience improves adherence compared to 3–7 day regimens 2
• Minimal disruption to intestinal flora reduces risk of C. difficile infection 2
• Low resistance rates: Only 2.6% resistance in initial E. coli infections, 5.7% at 9 months 2
• Safe in pregnancy for asymptomatic bacteriuria 2, 4