Is fosfomycin used the same way for treating uncomplicated urinary‑tract infection (UTI) in patients with chronic kidney disease (CKD), or does dosing need to be adjusted according to renal function?

Fosfomycin Dosing in Chronic Kidney Disease for Uncomplicated UTI

For patients with chronic kidney disease (CKD) and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m², fosfomycin can be used at the standard single 3-gram oral dose without adjustment for uncomplicated lower urinary tract infections (cystitis). 1

Standard Dosing Across Renal Function Levels

• No dose adjustment is required for mild to moderate renal impairment (eGFR ≥30 mL/min/1.73 m²), and the standard single 3-gram oral dose remains appropriate for uncomplicated cystitis. 1

• The single 3-gram dose provides therapeutic urinary concentrations for 24–48 hours, which is sufficient to eradicate most uropathogens causing uncomplicated lower UTI. 1

• Clinical efficacy remains approximately 91% for uncomplicated cystitis regardless of mild to moderate renal impairment. 1

Pharmacokinetic Considerations in Renal Impairment

• In anuric patients undergoing hemodialysis, the elimination half-life of fosfomycin increases dramatically from 5.7 hours to 40–50 hours, indicating significant accumulation in severe renal failure. 1, 2

• In patients with varying degrees of renal impairment (creatinine clearance 7–54 mL/min), the half-life increases from 11 to 50 hours, and urinary recovery decreases from 32% to 11%. 2

• Despite prolonged half-life in renal impairment, urinary concentrations remain therapeutic: elderly nursing-home patients with mean creatinine clearance of 40 mL/min achieved urinary fosfomycin concentrations of 1,383 mg/L in the first 12 hours and maintained levels >165 mg/L for 36–48 hours after a single 3-gram dose. 3

Critical Restrictions for Fosfomycin Use

• Fosfomycin is restricted to uncomplicated lower UTI (cystitis) only and should never be used for pyelonephritis, complicated UTIs, or upper urinary tract infections in patients with any degree of CKD. 1

• Patients with hypernatremia, cardiac insufficiency, or severe renal insufficiency should use fosfomycin with caution, particularly when considering intravenous formulations for carbapenem-resistant organisms. 1

Electrolyte Monitoring Requirements

• Fosfomycin can cause hypokalemia, hypocalcemia, hypomagnesemia, and hypernatremia, and monitoring electrolytes during and after treatment is recommended, particularly in patients with pre-existing renal dysfunction. 1

Clinical Efficacy in CKD Populations

• In a retrospective study of predominantly elderly patients (median age 79 years) with complicated and multidrug-resistant UTIs—many of whom likely had underlying renal impairment—fosfomycin achieved 96.4% clinical success and 75% microbiological cure. 4

• Another retrospective analysis of MDR UTIs treated with fosfomycin showed 55% treatment success overall, with chronic kidney disease identified as a predictor of persistent infection (OR = 3.56,95% CI = 1.02–12.40). 5

Algorithm for Fosfomycin Use in CKD

1. Confirm uncomplicated lower UTI (cystitis): no fever, flank pain, or systemic signs suggesting pyelonephritis. 1

2. Assess renal function:

   • eGFR ≥30 mL/min/1.73 m² → Use standard single 3-gram dose. 1
   • eGFR <30 mL/min/1.73 m² → Consider alternative agents (nitrofurantoin is contraindicated; trimethoprim-sulfamethoxazole or beta-lactams may be appropriate based on susceptibility). 1

3. Check for contraindications: hypernatremia, severe cardiac insufficiency, or severe electrolyte abnormalities. 1

4. Monitor electrolytes if the patient has CKD stage 3b or worse, particularly potassium, calcium, magnesium, and sodium. 1

5. If symptoms persist after 2–3 days or recur within 2 weeks, obtain urine culture and switch to a different antibiotic class for a 7-day course. 1

Common Pitfalls to Avoid

• Do not use fosfomycin for suspected pyelonephritis or upper UTI in CKD patients, as tissue penetration is inadequate and clinical efficacy data are lacking. 1

• Do not assume fosfomycin requires dose reduction in mild to moderate CKD; the standard single dose is appropriate and effective. 1

• Do not use fosfomycin for asymptomatic bacteriuria in non-pregnant CKD patients, as treatment offers no benefit and promotes resistance. 1

• Do not use multiple doses of fosfomycin for uncomplicated cystitis; the evidence-based regimen is a single 3-gram dose. 1