What is the first line treatment and dosage for an uncomplicated urinary tract infection (UTI)?

First-Line Treatment for Uncomplicated UTI

For uncomplicated cystitis in women, nitrofurantoin 100 mg twice daily for 5 days is the preferred first-line treatment, with fosfomycin 3 g single dose and trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days as alternatives when local E. coli resistance is below 20%. 1, 2

Treatment Options by Patient Population

Women with Uncomplicated Cystitis

First-line agents (in order of preference):

• Nitrofurantoin: 100 mg twice daily for 5 days 1, 2, 3

  • Preferred due to minimal resistance patterns and low collateral damage to gut flora
  • Achieves high urinary concentrations but should NOT be used for pyelonephritis or upper UTIs 2

• Fosfomycin trometamol: 3 g single dose 1, 4, 3

  • Convenient single-dose therapy
  • Must be mixed with water before ingesting, never taken in dry form 4
  • May have slightly inferior efficacy compared to 5-day nitrofurantoin courses 1, 2

• Pivmecillinam: 400 mg three times daily for 3-5 days 1

  • Only available in some European countries, not licensed in North America 1

Alternative agents (when first-line cannot be used):

• Trimethoprim-sulfamethoxazole: 160/800 mg (one double-strength tablet) twice daily for 3 days 1, 5, 3

  • Only use if local E. coli resistance rates are below 20% 2, 6
  • Rising resistance rates have limited its use as empiric therapy 2, 7

• Trimethoprim alone: 200 mg twice daily for 5 days 1

  • Not recommended in first trimester of pregnancy 1

• Cephalosporins (e.g., cefadroxil): 500 mg twice daily for 3 days 1

  • Only if local E. coli resistance is below 20% 1

Men with Uncomplicated UTI

Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 7 days is the standard treatment for men. 1, 3

• Men require longer treatment duration (7 days minimum) compared to women 1, 3
• Fluoroquinolones can be prescribed according to local susceptibility patterns 1
• Always obtain urine culture before treatment to guide antibiotic selection 3
• Consider urethritis and prostatitis as alternative diagnoses 3

Critical Prescribing Considerations

When to Avoid Specific Agents

Fluoroquinolones (ciprofloxacin, levofloxacin):

• Should be reserved as alternatives only when other agents cannot be used 1, 2
• Despite high efficacy, they cause significant collateral damage to normal flora and promote resistance 1, 2
• FDA has issued serious safety warnings regarding tendon, muscle, joint, nerve, and CNS effects 2

Beta-lactams (amoxicillin-clavulanate, cefpodoxime):

• Generally have inferior efficacy compared to first-line agents 1, 6
• Use only when recommended agents cannot be used 1
• Require 3-7 day regimens 1

Amoxicillin or ampicillin alone:

• Should NEVER be used for empiric treatment due to poor efficacy and very high resistance rates worldwide 1

Special Populations

Postmenopausal women:

• Same first-line agents and durations as premenopausal women 1, 3
• Consider vaginal estrogen replacement for recurrent UTI prevention 1

Women with diabetes:

• Treat identically to women without diabetes if no voiding abnormalities present 6
• Same first-line agents and durations 6

Adults ≥65 years:

• Obtain urine culture with susceptibility testing to adjust therapy after initial empiric treatment 3
• First-line antibiotics and durations do not differ from younger adults 3

Treatment Duration Evidence

The 5-day nitrofurantoin regimen balances efficacy with minimizing adverse effects and resistance. 2

• Three-day courses achieve similar symptomatic cure but lower bacteriological cure rates compared to 5-10 day courses 8
• UK guidelines promoting 3-day nitrofurantoin courses lack direct supporting evidence 9
• The European Association of Urology recommends 5 days for nitrofurantoin 1
• Longer courses (5-10 days) have significantly more adverse effects 8

Common Pitfalls to Avoid

Do NOT obtain urine culture for routine uncomplicated cystitis in women:

• Self-diagnosis with typical symptoms (frequency, urgency, dysuria, suprapubic pain) without vaginal discharge is sufficiently accurate 3
• Reserve cultures for: recurrent infection, treatment failure, history of resistant organisms, or atypical presentation 3

Do NOT use nitrofurantoin for:

• Pyelonephritis or upper UTIs (inadequate tissue concentrations) 2
• Infants under 4 months (risk of hemolytic anemia) 2

Do NOT treat asymptomatic bacteriuria:

• Treatment does not improve outcomes and promotes antimicrobial resistance 2

When Treatment Fails

If symptoms do not resolve by end of treatment or recur within 2 weeks:

• Obtain urine culture and antimicrobial susceptibility testing 1
• Assume the organism is not susceptible to the original agent 1
• Retreat with a 7-day regimen using a different agent 1