What is the recommended dose of Fosfomycin for a patient with a urinary tract infection (UTI) and potential impaired renal function?

Fosfomycin Dosing for Urinary Tract Infections

For uncomplicated UTI in women, administer a single 3-gram oral dose of fosfomycin tromethamine, which can be taken with or without food and requires no dose adjustment for renal impairment. 1

Standard Dosing by Clinical Scenario

Uncomplicated Cystitis in Women

• Single 3-gram oral dose is the FDA-approved regimen, providing therapeutic urinary concentrations (>128 mg/L) for 24-48 hours, which is sufficient to eradicate most uropathogens 1, 2
• This single-dose regimen is recommended as first-line therapy by the American Urological Association, European Association of Urology, and American College of Physicians 2, 3
• The medication should be mixed with water before ingesting and never taken in dry form 1

Complicated Lower UTI (Off-Label)

• For complicated lower UTI, use 3 grams orally every 48-72 hours for a total of 3 doses (days 1,3, and 5) 4, 5
• This regimen is appropriate for patients who have failed other treatments, are infected with multidrug-resistant organisms, or cannot tolerate first-line agents 4
• Clinical efficacy rates with this three-dose regimen are 62.69% for complicated lower UTI and 77.22% for recurrent lower UTI 5

Upper UTI/Pyelonephritis

• Oral fosfomycin should NOT be used for pyelonephritis or complicated upper UTI due to insufficient efficacy data 2, 3
• If fosfomycin is required for upper UTI, intravenous formulation at 6 grams every 8 hours for 7 days (14 days with concurrent bacteremia) should be used instead 4
• Fluoroquinolones or β-lactams are preferred for oral treatment of pyelonephritis 2

Renal Impairment Considerations

Pharmacokinetic Changes

• No dose adjustment is required for oral fosfomycin in renal impairment when treating uncomplicated cystitis with the single-dose regimen 1
• The elimination half-life increases dramatically from 5.7 hours in normal renal function to 40-50 hours in anuric patients 1, 2
• Urinary excretion decreases from 38% to 11% as creatinine clearance declines, but the single 3-gram dose still achieves adequate urinary concentrations 1

Important Cautions

• Use fosfomycin with caution in patients with hypernatremia, cardiac insufficiency, or severe renal insufficiency, particularly when considering IV formulations for carbapenem-resistant organisms 2
• The FDA label notes that renal impairment significantly decreases fosfomycin excretion, but does not mandate dose reduction for the single-dose oral regimen 1

Special Populations

Pregnancy

• Fosfomycin is safe in pregnancy (FDA Category B) and is recommended for asymptomatic bacteriuria in pregnant women as either standard short-course or single-dose treatment 2, 3, 6
• Single-dose fosfomycin 3 grams has similar bacteriological efficacy to 5-7 day courses of cefuroxime or amoxicillin-clavulanate in pregnant women 6

Men

• Fosfomycin is NOT recommended for routine use in men with UTIs due to limited clinical efficacy data in this population 2

Elderly

• No dosage adjustment is necessary in elderly patients based on 24-hour urinary drug concentration data 1

Clinical Efficacy and Resistance

Spectrum of Activity

• Fosfomycin maintains excellent activity against common uropathogens including E. coli (including ESBL-producing strains), VRE, and MRSA with only 2.6% resistance prevalence in initial E. coli infections 2, 7
• The drug has minimal cross-resistance with other antibiotic classes due to its unique mechanism of inhibiting bacterial cell wall synthesis 1, 7

Comparative Efficacy

• Clinical efficacy is comparable to 3-7 day regimens of other first-line agents (nitrofurantoin, trimethoprim-sulfamethoxazole, fluoroquinolones), though bacteriological efficacy may be somewhat lower 2, 8, 6
• The IDSA notes slightly inferior efficacy compared to 3-day trimethoprim-sulfamethoxazole or fluoroquinolones based on FDA submission data, but fosfomycin remains appropriate first-line therapy due to minimal resistance and collateral damage 2

Administration and Food Effects

Optimal Administration

• Fosfomycin may be taken with or without food, though food reduces bioavailability from 37% (fasting) to 30% (fed) and delays peak concentration from 2 to 4 hours 1
• Despite reduced absorption with food, the cumulative urinary excretion remains the same (1,118 mg fed vs 1,140 mg fasting), and urinary concentrations >100 mcg/mL are maintained for 26 hours regardless of food intake 1

Drug Interactions

• Avoid co-administration with metoclopramide, which lowers serum concentrations and urinary excretion of fosfomycin 1
• Cimetidine does not affect fosfomycin pharmacokinetics 1

Common Pitfalls to Avoid

• Do not use oral fosfomycin for pyelonephritis, febrile UTI, or complicated upper UTI - this is the most critical error, as insufficient data support efficacy in these conditions 9, 2
• Do not prescribe fosfomycin routinely for men - limited efficacy data exists for this population 2
• Do not use multiple doses for uncomplicated cystitis in women - the single 3-gram dose is sufficient and FDA-approved 1
• Do not assume fosfomycin requires dose adjustment for renal impairment in uncomplicated UTI - the single-dose regimen does not require modification 1

Safety Profile

• The most common adverse events are gastrointestinal (diarrhea, nausea, vomiting), occurring in approximately 5.6% of patients 5, 2
• Fosfomycin has minimal disruption to intestinal flora compared to fluoroquinolones and cephalosporins, reducing risk of C. difficile infection 2
• No serious drug-related adverse events were reported in clinical trials 5