What is the drug of choice for uncomplicated cystitis in an otherwise healthy non‑pregnant adult?

Drug of Choice for Uncomplicated Cystitis

Nitrofurantoin monohydrate/macrocrystals 100 mg twice daily for 5 days is the drug of choice for uncomplicated cystitis in otherwise healthy non-pregnant adults. 1

Why Nitrofurantoin is First-Line

• The Infectious Diseases Society of America (IDSA) recommends nitrofurantoin as first-line therapy due to minimal resistance patterns, limited collateral damage to normal flora, and efficacy comparable to other agents. 1

• Clinical cure rates reach 88-93% and bacterial cure rates achieve 81-92% in patients with uncomplicated cystitis. 1, 2

• Nitrofurantoin preserves more systemically active antibiotics (like fluoroquinolones) for serious infections while maintaining excellent activity against common uropathogens. 1

Dosing and Duration

• Prescribe 100 mg orally twice daily for 5 days for uncomplicated UTI in women. 1, 2

• A 7-day course (100 mg twice daily) is acceptable and achieves clinical cure rates of 89-93%, though 5 days is the preferred duration. 2

• Avoid 3-day regimens (100 mg four times daily), which show inferior efficacy with only 88% clinical cure and 74% bacterial cure rates. 2

Critical Contraindications

• Do not use nitrofurantoin if creatinine clearance is <60 mL/min (some sources cite <30 mL/min as the absolute cutoff), as inadequate urinary drug concentrations prevent bactericidal activity and increase toxicity risk. 1, 2

• Never use for suspected pyelonephritis, as nitrofurantoin does not achieve adequate tissue concentrations for upper tract infections. 2

Alternative First-Line Options (When Nitrofurantoin Cannot Be Used)

Trimethoprim-Sulfamethoxazole (TMP-SMX)

• Prescribe 160/800 mg (one double-strength tablet) twice daily for 3 days only if local E. coli resistance is <20% and the patient has not received TMP-SMX in the preceding 3 months. 1, 3

• Clinical cure rates reach 90-100% when organisms are susceptible, but plummet to 41-54% for resistant strains. 1, 3

• The 20% resistance threshold is based on expert consensus integrating clinical outcomes, in-vitro data, and mathematical modeling—above this level, treatment failures outweigh benefits. 1, 3

Fosfomycin Trometamol

• Prescribe 3 g as a single oral dose when nitrofurantoin is contraindicated (e.g., eGFR <30 mL/min) or when adherence to multi-day regimens is doubtful. 1, 4

• Clinical cure rates reach 90-91%, but microbiologic cure rates are lower at 78-80% compared to nitrofurantoin. 1

• Avoid if early pyelonephritis is suspected, as fosfomycin is FDA-indicated only for acute cystitis, not upper tract infections. 1, 4

Reserve (Second-Line) Options

Fluoroquinolones

• Ciprofloxacin 250 mg twice daily for 3 days or levofloxacin achieve high clinical cure rates (~95%) and bacteriologic eradication rates of 93-97%. 1, 3

• Reserve fluoroquinolones for situations where first-line agents are unsuitable due to concerns about promoting resistance, collateral damage to normal flora, and the need to preserve these agents for more serious infections like pyelonephritis. 1, 3

Oral β-Lactams

• Agents like cefdinir, cefaclor, cefpodoxime-proxetil, or cephalexin (3-7 days) may be used only when no recommended first-line agents are available. 1

• These agents generally have inferior efficacy compared to nitrofurantoin or TMP-SMX and more adverse effects. 1

Agents to Avoid

• Never use amoxicillin or ampicillin empirically for uncomplicated cystitis due to poor efficacy and globally high resistance rates among uropathogens. 1, 3

Common Pitfalls

• Do not prescribe TMP-SMX without knowing local resistance patterns—hospital antibiograms often overestimate community resistance, so seek outpatient surveillance data when available. 3

• Do not use fluoroquinolones as first-line therapy despite their high efficacy, as this promotes resistance to agents needed for pyelonephritis and other serious infections. 1, 3

• Assess renal function before prescribing nitrofurantoin—if eGFR <30 mL/min, switch to fosfomycin 3 g single dose. 1

• Avoid TMP-SMX in patients with recent travel outside the United States (preceding 3-6 months) or recent TMP-SMX use, as these factors independently predict resistance. 3

Expected Adverse Effects

• Nausea and headache are the most common adverse effects with nitrofurantoin, occurring in 5.6-34% of patients, with rates comparable to TMP-SMX (31-38%). 2