What oral fosfomycin dosing regimen is recommended for an adult with end‑stage renal disease and a urinary tract infection, including timing relative to intermittent hemodialysis?

Fosfomycin Dosing for UTI in ESRD Patients

For adults with end-stage renal disease and urinary tract infections, oral fosfomycin tromethamine 3 grams as a single dose remains the standard regimen, with no dose adjustment required for renal impairment, though efficacy may be reduced compared to patients with normal renal function.

Standard Dosing Recommendation

• A single oral dose of fosfomycin tromethamine 3 grams is recommended for uncomplicated UTI in ESRD patients 1, 2
• No dose adjustment is necessary based on creatinine clearance, as fosfomycin is not metabolized and is excreted unchanged in urine 3
• The medication should be administered after hemodialysis on dialysis days to facilitate directly observed therapy and avoid premature drug clearance 1

Pharmacokinetic Considerations in ESRD

• Following a single 3-gram oral dose, peak urinary concentrations of 1053-4415 mg/L occur within 4 hours in patients with normal renal function 3
• Urinary concentrations remain >128 mg/L (adequate to inhibit most uropathogens) for 24-48 hours after dosing 2, 3
• In ESRD patients, urinary drug concentrations will be substantially lower due to minimal glomerular filtration, though specific pharmacokinetic data in this population are limited 4
• Oral bioavailability is only 34-41%, which further limits systemic and urinary drug exposure 2

Efficacy Limitations in ESRD

• The bacterial eradication rate of fosfomycin (75-90% at 5-11 days) is lower than other first-line agents even in patients with normal renal function 1
• Clinical efficacy depends on achieving adequate urinary concentrations, which may not occur in anuric or severely oliguric ESRD patients 4
• Baseline heteroresistance (high-level resistant subpopulations present in 50% of isolates) predicts treatment failure regardless of drug exposure 5

Alternative Multi-Dose Regimens

While not specifically studied in ESRD, three doses of 3 grams given on days 1,3, and 5 showed improved efficacy for complicated lower UTI in patients with normal renal function (clinical efficacy 62.69% vs single-dose regimens) 6

However, multiple dosing provides limited additional bacterial kill in pharmacodynamic modeling, particularly when baseline heteroresistance is present 5

Critical Caveats for ESRD Patients

• Fosfomycin should NOT be first-line therapy in ESRD patients with UTI due to unpredictable urinary concentrations and lower efficacy 1, 4
• Consider fosfomycin only when treating multidrug-resistant organisms (VRE, ESBL-producing gram-negatives) where no other oral options exist 1
• A disk diffusion zone <24 mm predicts baseline heteroresistance and treatment failure better than MIC alone 5
• Fosfomycin monotherapy should be avoided for complicated infections; combination therapy may be necessary 4

Preferred Alternatives in ESRD

For ESRD patients requiring UTI treatment, consider:

• Nitrofurantoin 100 mg every 6 hours (though contraindicated if CrCl <30 mL/min in some guidelines) 1
• Aminoglycosides as single-dose therapy (15 mg/kg 2-3 times weekly post-dialysis for complicated UTI) 1
• Beta-lactams with appropriate renal dosing (various agents require dose/frequency adjustment) 1

Timing with Hemodialysis

• Always administer fosfomycin after hemodialysis to prevent premature drug removal and facilitate adherence 1, 7
• This timing principle applies to most renally cleared antimicrobials in ESRD 1