What medications are given to a non-pregnant, otherwise healthy adult woman with an acute uncomplicated urinary tract infection (UTI)?

First-Line Medications for Acute Uncomplicated UTI

For acute uncomplicated urinary tract infection in non-pregnant, otherwise healthy adult women, use nitrofurantoin 100 mg twice daily for 5 days, fosfomycin trometamol 3 g single dose, or trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days as first-line therapy, with the choice dependent on local resistance patterns. 1

First-Line Treatment Options

The 2024 European Association of Urology guidelines and 2019 AUA/CUA/SUFU guidelines establish three primary first-line agents 1:

Nitrofurantoin (Preferred in Many Settings)

• Nitrofurantoin monohydrate/macrocrystals: 100 mg twice daily for 5 days 1
• Alternative dosing: 50-100 mg four times daily for 5 days 1
• Avoid if early pyelonephritis is suspected (inadequate tissue penetration) 1
• Lower risk of antimicrobial resistance compared to other agents 1
• Recent evidence suggests nitrofurantoin may have lower treatment failure rates than trimethoprim-sulfamethoxazole 2

Fosfomycin Trometamol

• 3 g single dose 1
• Recommended only for women with uncomplicated cystitis 1
• Convenient single-dose regimen improves compliance 1
• Lower efficacy than some other first-line agents; avoid if early pyelonephritis suspected 1

Trimethoprim-Sulfamethoxazole (TMP-SMX)

• 160/800 mg (one double-strength tablet) twice daily for 3 days 1, 3
• Only use if local E. coli resistance is <20% 1
• Avoid if patient used TMP-SMX for UTI in previous 3 months 1
• Increasing resistance rates limit its use in many communities 1, 2
• Not recommended in first trimester of pregnancy 1

Pivmecillinam (Where Available)

• 400 mg three times daily for 3-5 days 1
• Not available in the United States 1
• Lower efficacy than some other recommended agents 1

Second-Line/Alternative Agents

When first-line agents cannot be used due to resistance patterns, allergies, or availability 1:

Cephalosporins

• Cefadroxil 500 mg twice daily for 3 days (or comparable cephalosporin) 1
• Only if local E. coli resistance <20% 1
• Generally have inferior efficacy and more adverse effects compared to first-line agents 1

Fluoroquinolones (Use Restricted)

• Ciprofloxacin 250-500 mg twice daily for 3 days 4
• Levofloxacin 250 mg daily for 3 days 1
• Not recommended as first-line due to collateral damage and serious FDA safety warnings 1
• High resistance prevalence in many areas precludes empiric use 1, 5
• Reserve for complicated cases or when other options unavailable 1

Trimethoprim Alone

• 200 mg twice daily for 5 days 1
• Not in first trimester of pregnancy 1

Treatment Duration Principles

Keep antibiotic courses as short as reasonable, generally no longer than 7 days 1:

• 3-5 days for most first-line agents 1
• Shorter courses reduce adverse effects and antimicrobial resistance 1
• Longer courses do not improve outcomes in uncomplicated UTI 1

Critical Pitfalls to Avoid

Do Not Use These Agents

• Amoxicillin or ampicillin should NOT be used empirically due to very high resistance rates worldwide 1
• Beta-lactams other than pivmecillinam should be used with caution due to inferior efficacy and higher adverse effects 1

When to Obtain Urine Culture

Urine culture is NOT needed for typical uncomplicated cystitis but IS required for 1:

• Suspected acute pyelonephritis
• Symptoms not resolving or recurring within 4 weeks after treatment
• Atypical symptoms
• Pregnant women
• Recurrent UTI patients (before each episode) 1

Treatment Failure Management

If symptoms do not resolve by end of treatment or recur within 2 weeks 1:

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

Special Considerations for Men

Men with uncomplicated UTI require longer treatment duration 1:

• Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 7 days 1
• Fluoroquinolones can be prescribed according to local susceptibility 1
• Always obtain urine culture in men 6
• Consider urethritis and prostatitis as alternative diagnoses 6

Resistance Pattern Considerations

The choice between first-line agents must account for local resistance patterns 1:

• If TMP-SMX resistance >20% in your community, choose nitrofurantoin or fosfomycin 1
• Recent TMP-SMX exposure increases treatment failure risk 2
• Fluoroquinolone resistance is high in many areas, limiting their utility 1, 5
• Nitrofurantoin maintains low resistance rates due to lack of cross-resistance with commonly prescribed antimicrobials 7