What is the first‑line oral treatment for an otherwise healthy adult with uncomplicated cystitis (urinary tract infection)?

First-Line Treatment for Uncomplicated Cystitis

Nitrofurantoin monohydrate/macrocrystals 100 mg twice daily for 5 days is the preferred first-line oral treatment for otherwise healthy adults with uncomplicated cystitis. 1, 2

Primary Recommendation

• Nitrofurantoin achieves clinical cure rates of 88-93% and bacterial cure rates of 81-92%, with minimal resistance patterns and limited collateral damage to normal flora. 1, 2
• This agent is endorsed by both the Infectious Diseases Society of America and the European Association of Urology as first-line therapy. 1, 2
• The 5-day duration is necessary for optimal efficacy, unlike some other agents that can be given for shorter courses. 1, 2

Alternative First-Line Options (when nitrofurantoin cannot be used)

Fosfomycin trometamol

• Single 3-gram oral dose provides clinical cure rates of 90-91%, though microbiologic cure rates are slightly lower at 78-80%. 1, 2
• Particularly useful when adherence to multi-day regimens is questionable or when renal function is impaired (eGFR <30 mL/min, where nitrofurantoin is contraindicated). 2, 3
• Should be mixed with water before ingesting; never taken in dry form. 4

Trimethoprim-sulfamethoxazole (TMP-SMX)

• 160/800 mg (one double-strength tablet) twice daily for 3 days is appropriate only if local E. coli resistance is documented to be <20%. 1, 2
• When organisms are susceptible, cure rates reach 90-100%; however, when resistant, cure rates plummet to only 41-54%. 1, 5
• Do not use empirically if the patient has taken TMP-SMX in the preceding 3 months or has traveled outside the United States in the preceding 3-6 months, as these factors predict resistance. 5

Pivmecillinam

• 400 mg twice daily for 3-5 days is an option in European countries where available (not licensed in North America). 1
• Has minimal collateral damage but slightly lower efficacy than other first-line agents. 2

Reserve (Second-Line) Agents

Fluoroquinolones

• Ciprofloxacin 250 mg twice daily for 3 days or levofloxacin achieve bacteriologic eradication rates of 93-97%. 1, 5
• Should be reserved for more serious infections (such as pyelonephritis) rather than simple cystitis due to concerns about promoting resistance and collateral damage to normal flora. 1, 2
• Use only when first-line agents are contraindicated or unavailable. 1, 2

Oral β-lactams

• Agents such as cefdinir, cefaclor, cefpodoxime-proxetil, or cephalexin given for 3-7 days are options only when recommended first-line agents cannot be used. 1
• These agents have inferior efficacy and more adverse effects compared to nitrofurantoin or TMP-SMX. 1, 2
• Amoxicillin-clavulanate may be considered but shares the same limitations as other β-lactams. 1

Agents to Avoid

• Amoxicillin or ampicillin alone should never be used empirically due to very high worldwide resistance rates (often >30%) and poor efficacy. 1, 5

Clinical Decision Algorithm

1. Assess renal function:

   • If eGFR >30 mL/min → prescribe nitrofurantoin 100 mg twice daily for 5 days. 2, 3
   • If eGFR <30 mL/min → prescribe fosfomycin 3 g single dose. 2, 3

2. If nitrofurantoin is contraindicated (allergy, renal impairment, or other reason):

   • Check local E. coli resistance rates to TMP-SMX:
     • If <20% resistance and no recent TMP-SMX use → TMP-SMX 160/800 mg twice daily for 3 days. 1, 2
     • If ≥20% resistance or recent use → fosfomycin 3 g single dose. 1, 2

3. If both nitrofurantoin and fosfomycin are unavailable or contraindicated:

   • Consider fluoroquinolone (ciprofloxacin 250 mg twice daily for 3 days) as a reserve option. 1, 5
   • Alternatively, use oral cephalosporin (e.g., cephalexin) for 3-7 days, recognizing lower efficacy. 1

Important Caveats and Pitfalls

• Do not use TMP-SMX empirically without knowing local resistance patterns; hospital antibiograms often overestimate community resistance, so outpatient surveillance data is more accurate. 5
• Do not extend nitrofurantoin beyond 7 days or use it when eGFR <30 mL/min, as this increases toxicity risk without improving outcomes. 3
• Avoid fluoroquinolones as first-line therapy despite their high efficacy, as this promotes resistance to agents needed for more serious infections like pyelonephritis. 1, 2
• Urine culture is not routinely needed for typical uncomplicated cystitis in otherwise healthy women; reserve cultures for atypical presentations, treatment failures, or recurrence within 2-4 weeks. 1, 6
• Immediate antimicrobial therapy is superior to delayed treatment or symptom management with ibuprofen alone. 7

Special Populations

Men with uncomplicated cystitis

• Require 7 days of therapy (not 3 days) with TMP-SMX 160/800 mg twice daily. 1, 5
• Short-course regimens effective in women are inadequate for men. 5

Pregnant women

• Avoid TMP-SMX in the last trimester due to potential fetal risks. 1, 5
• Nitrofurantoin and fosfomycin remain appropriate options. 1