What is the best first‑line oral antibiotic for uncomplicated acute cystitis in an adult patient with end‑stage renal disease on intermittent hemodialysis?

Best Antibiotic for Acute Cystitis in ESRD

For adult patients with end-stage renal disease on hemodialysis presenting with uncomplicated acute cystitis, fosfomycin trometamol 3 g as a single oral dose is the preferred first-line therapy. 1

Rationale for Fosfomycin in ESRD

• Fosfomycin provides adequate urinary concentrations without requiring dose adjustment for any degree of renal impairment, including ESRD, with clinical cure rates of 90–91% and microbiological cure rates of 78–80%. 1
• The single 3-gram dose achieves therapeutic urinary concentrations for 24–48 hours, which is sufficient to eradicate most uropathogens even in patients with severely compromised renal function. 2
• Fosfomycin is effective in patients with eGFR <60 mL/min, resulting in only 16.0% clinical failures compared to 23.3% with nitrofurantoin. 1
• The drug maintains excellent activity against E. coli (the causative organism in 75–95% of uncomplicated cystitis cases) with resistance rates of only 2.6% in initial infections. 2

Why Nitrofurantoin Is Contraindicated

• Nitrofurantoin is absolutely contraindicated when eGFR is <30 mL/min/1.73 m² (which includes all ESRD patients) due to reduced efficacy and increased risk of toxicity. 1
• Urinary drug concentrations become insufficient for bacterial eradication in severe renal impairment, leading to treatment failure. 1
• Using nitrofurantoin in patients with severely impaired renal function can lead to accumulation of toxic metabolites and increased adverse effects. 1

Alternative Second-Line Options (When Fosfomycin Cannot Be Used)

• Fluoroquinolones (ciprofloxacin 500 mg twice daily for 7 days) may be considered when first-line agents cannot be used, though they should be reserved for culture-proven resistant organisms due to concerns about promoting resistance and serious adverse effects. 1
• Fluoroquinolones do not require dose adjustment in ESRD patients on hemodialysis for short courses, though longer courses may require modification. 1
• Oral cephalosporins (cefdinir, cefpodoxime-proxetil) can be used for 3–7 days when other recommended agents cannot be used, but they have inferior efficacy (approximately 89% clinical cure and 82% microbiological cure) compared to fosfomycin. 1, 2

Critical Management Steps

• Obtain urine culture with susceptibility testing before initiating therapy in ESRD patients, as this complicated population requires culture-guided therapy to ensure appropriate antibiotic selection. 1
• Verify that the patient does not have upper tract involvement (fever, flank pain, costovertebral angle tenderness), as fosfomycin is not recommended for pyelonephritis. 1, 2
• Re-evaluate the patient 2–3 days after therapy initiation; lack of symptom improvement may indicate resistance or an alternative diagnosis. 1

Common Pitfalls to Avoid

• Do not prescribe trimethoprim-sulfamethoxazole without verifying susceptibility, as resistance rates exceed 20% in many communities and treatment failure is unacceptably high when resistance is present. 1
• Do not use amoxicillin or ampicillin empirically, as global resistance rates exceed 55–67% and efficacy is poor for uncomplicated cystitis. 1, 2
• Do not extend fosfomycin beyond the single 3-gram dose for uncomplicated cystitis, as the standard single-dose regimen is the evidence-based approach. 2
• Do not assume all "penicillin allergies" are true IgE-mediated reactions; many are intolerances, but formal assessment is advisable before using cephalosporins in patients reporting penicillin allergy. 1

Special Considerations for Hemodialysis Patients

• Fosfomycin's elimination half-life increases from 5.7 hours to 40–50 hours in anuric patients, but the single 3-gram dose remains appropriate and does not require adjustment. 2
• Patients with hypernatremia, cardiac insufficiency, or fluid overload should use fosfomycin with caution, particularly if considering IV formulations for more severe infections. 2
• The convenience of single-dose therapy improves adherence and eliminates concerns about timing doses around dialysis sessions. 2