First-Line Antibiotic for Uncomplicated Cystitis
Nitrofurantoin monohydrate/macrocrystals 100 mg twice daily for 5 days is the preferred first-line oral regimen for otherwise healthy adults with uncomplicated cystitis and no β-lactam allergy. 1
Why Nitrofurantoin Is First-Line
Nitrofurantoin achieves clinical cure rates of 88–93% and microbiologic cure rates of 81–92%, comparable to fluoroquinolones and trimethoprim-sulfamethoxazole but with minimal resistance and limited collateral damage to normal flora. 1
The Infectious Diseases Society of America and European Association of Urology both endorse nitrofurantoin as the preferred agent due to its minimal resistance patterns and preservation of more systemically active antibiotics for serious infections. 1, 2
The 5-day duration is required for optimal efficacy—shorter courses are insufficient. 1
Alternative First-Line Options (When Nitrofurantoin Cannot Be Used)
If nitrofurantoin is contraindicated (e.g., eGFR < 30 mL/min) or unavailable, consider these alternatives in order:
Fosfomycin trometamol 3 g as a single oral dose provides clinical cure rates of 90–91% but lower microbiologic cure rates of 78–80%. 1 It is especially useful when adherence to multi-day regimens is doubtful, but avoid if early pyelonephritis is suspected due to inferior microbiologic efficacy. 1
Trimethoprim-sulfamethoxazole (TMP-SMX) 160/800 mg twice daily for 3 days is appropriate only if local E. coli resistance is < 20% and the patient has not received TMP-SMX for a UTI in the preceding 3 months. 1 In susceptible infections, cure rates reach 90–100%, but resistance drops efficacy to 41–54%. 1
Pivmecillinam 400 mg twice daily for 3–5 days is available only in Europe and has slightly lower efficacy than nitrofurantoin or TMP-SMX, but minimal collateral damage. 1, 2
Reserve (Second-Line) Agents—Use Only When First-Line Options Are Unsuitable
Fluoroquinolones (ciprofloxacin 250 mg twice daily or levofloxacin for 3 days) achieve bacteriologic eradication rates of 93–97%, but should be reserved for more serious infections (e.g., pyelonephritis) to limit resistance development. 1, 2
Oral β-lactams (cefdinir, cefaclor, cefpodoxime-proxetil, cephalexin) for 3–7 days demonstrate inferior efficacy and higher adverse-event rates compared with nitrofurantoin or TMP-SMX. 1 Use only when no first-line agents are available.
Agents to Avoid
Amoxicillin or ampicillin alone should never be used empirically because worldwide resistance exceeds 30%, resulting in poor therapeutic outcomes. 1, 2
Fluoroquinolones as first-line therapy should be avoided despite high efficacy, to preserve their utility for serious infections. 1, 2
Diagnostic Considerations
Diagnosis is based on dysuria, urinary frequency, urgency, or suprapubic tenderness without fever, flank pain, or other signs of pyelonephritis. 1
Urine culture is not routinely required for typical uncomplicated cystitis in otherwise healthy women; reserve it for atypical presentations, treatment failures, or recurrence within 2–4 weeks. 1, 2
Common Pitfalls to Avoid
Do not prescribe TMP-SMX empirically without knowledge of local resistance patterns or if the patient received it recently. 1, 2
Do not use fluoroquinolones as first-line therapy even though they are highly effective—this promotes resistance to agents needed for more serious infections. 1, 2
Do not use fosfomycin if early pyelonephritis is suspected, as its microbiologic cure rates are lower than nitrofurantoin's. 1
Ensure the full 5-day course of nitrofurantoin is prescribed—shorter durations are inadequate. 1