What is the first-line treatment for acute uncomplicated cystitis, nitrofurantoin or fosfomycin?

First-Line Treatment for Acute Uncomplicated Cystitis

Nitrofurantoin monohydrate/macrocrystals (100 mg twice daily for 5 days) is the preferred first-line treatment for acute uncomplicated cystitis, with fosfomycin trometamol (3 g single dose) serving as an appropriate alternative first-line option. 1

Primary Recommendation: Nitrofurantoin

The Infectious Diseases Society of America (IDSA) explicitly recommends nitrofurantoin monohydrate/macrocrystals as first-line therapy due to minimal resistance patterns and limited collateral damage to normal flora. 1 This recommendation is supported by robust efficacy data:

• Clinical cure rates: 88-93% 1, 2
• Bacterial cure rates: 81-92% 1, 2
• Comparable efficacy to ciprofloxacin (93% vs 95%) and trimethoprim-sulfamethoxazole (93% vs 95%) 1

The standard dosing regimen is 100 mg twice daily for 5-7 days, with the 5-day course being optimal per IDSA and European Society for Microbiology and Infectious Diseases guidelines. 1, 2

Alternative First-Line Option: Fosfomycin

Fosfomycin trometamol (3 g single dose) represents an appropriate alternative when nitrofurantoin cannot be used, though it demonstrates slightly inferior microbiological efficacy. 1, 3

• Clinical cure rates: approximately 90% 1
• Microbiological cure rates: 78% (compared to 86% for nitrofurantoin) 1

The single-dose convenience makes fosfomycin particularly useful for patients with adherence concerns or those with renal impairment (eGFR <30 mL/min where nitrofurantoin is contraindicated). 3

Why Nitrofurantoin Takes Priority

While both agents are listed as first-line options in guidelines, nitrofurantoin is positioned ahead of fosfomycin for several reasons:

• Superior microbiological cure rates (86% vs 78%) 1
• More extensive clinical experience and documentation 2, 4
• Explicitly recommended as THE first-line agent by IDSA before listing alternatives 1
• Minimal resistance development over 60+ years of use 5

Clinical Algorithm for Selection

Start with nitrofurantoin 100 mg twice daily for 5 days UNLESS: 1, 2

1. eGFR <30 mL/min → Use fosfomycin 3 g single dose instead 3
2. Suspected early pyelonephritis → Avoid nitrofurantoin; consider fluoroquinolones 2
3. Patient has sulfa AND penicillin allergies → Fosfomycin is appropriate alternative 1
4. Adherence concerns with multi-day regimen → Consider fosfomycin single dose 3

Other First-Line Considerations

Trimethoprim-sulfamethoxazole (160/800 mg twice daily for 3 days) is technically first-line ONLY when local E. coli resistance rates are documented to be <20% or the infecting strain is confirmed susceptible. 1, 4 Given widespread resistance exceeding 20% in many regions, this option is increasingly limited.

Critical Contraindications and Pitfalls

Avoid nitrofurantoin when: 2, 3

• eGFR <30 mL/min (reduced efficacy and increased toxicity risk)
• Early pyelonephritis is suspected (inadequate tissue penetration)
• Last trimester of pregnancy

Common prescribing errors to avoid: 1

• Using fluoroquinolones as first-line therapy despite high efficacy (reserve for complicated infections to prevent resistance)
• Prescribing amoxicillin or ampicillin empirically (poor efficacy due to high resistance rates worldwide)
• Using β-lactams as first-line agents (inferior efficacy compared to nitrofurantoin and fosfomycin)

Comparative Context with Other Agents

Fluoroquinolones (ciprofloxacin, levofloxacin) achieve 95% clinical cure rates but should be reserved as alternative agents due to their propensity for collateral damage and promotion of resistance. 1, 4 β-lactam agents (amoxicillin-clavulanate, cefdinir, cefpodoxime) should only be used when first-line agents cannot be utilized, as they demonstrate inferior efficacy and more adverse effects. 1, 6