What is the first line treatment for uncomplicated urinary tract infections (UTIs)?

First-Line Treatment for Uncomplicated UTI

For uncomplicated UTI in women, use nitrofurantoin 100 mg twice daily for 5 days, fosfomycin trometamol 3 grams as a single dose, or pivmecillinam 400 mg three times daily for 3-5 days as first-line therapy. 1

Recommended First-Line Antibiotics for Women

The European Association of Urology establishes three equally acceptable first-line options for uncomplicated cystitis in women: 1

• Nitrofurantoin 100 mg twice daily for 5 days - preferred due to minimal resistance problems and multiple available formulations (macrocrystals, monohydrate, macrocrystals prolonged release) 1
• Fosfomycin trometamol 3 grams as a single dose - offers one-time dosing convenience and is FDA-approved specifically for uncomplicated bladder infections in women 1, 2
• Pivmecillinam 400 mg three times daily for 3-5 days 1

These agents are prioritized because they maintain high microbiological activity against UTI pathogens while minimizing collateral damage to protective periurethral and vaginal microbiota. 3, 4

Second-Line Options (Use Only When First-Line Unavailable)

• Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days - only if local E. coli resistance rates are below 20% 1, 5
• Trimethoprim alone 200 mg twice daily for 5 days 1
• Cephalosporins (e.g., cefadroxil 500 mg twice daily for 3 days) - only if local E. coli resistance is <20% 1

Critical Pitfall: Avoid Fluoroquinolones as First-Line

Fluoroquinolones should NOT be used for uncomplicated UTIs. 3 The FDA issued an advisory warning in July 2016 that fluoroquinolones have an unfavorable risk-benefit ratio for uncomplicated UTIs due to disabling and serious adverse effects. 3 Additionally, fluoroquinolones cause significant collateral damage by altering fecal microbiota and increasing risk of Clostridium difficile infection. 3

Treatment in Men

For men with uncomplicated UTI, the approach differs: 1

• Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 7 days (note the longer 7-day duration compared to women) 1
• Fluoroquinolones can be prescribed according to local susceptibility testing 1

When Antibiotics May Not Be Necessary

For women with mild to moderate symptoms, symptomatic therapy with ibuprofen may be considered as an alternative to antimicrobial treatment after discussing with the patient. 1

When to Obtain Urine Culture

Urine culture is NOT needed for typical uncomplicated cystitis in women. 1 However, obtain culture before treatment in these situations: 1

• Suspected acute pyelonephritis
• Symptoms not resolving or recurring within 4 weeks after treatment completion
• Atypical symptoms
• Pregnancy
• History of resistant organisms

Treatment Failure Protocol

If symptoms persist after completing antibiotics: 1

1. Obtain urine culture with antimicrobial susceptibility testing
2. Assume the organism is resistant to the initially used agent
3. Retreat with a 7-day regimen using a different antibiotic class

Symptoms should improve within 2-3 days of starting appropriate antibiotic therapy; if no improvement occurs by this timeframe, reassess the diagnosis and consider treatment failure. 1

Resistance Considerations

In a cohort examining E. coli UTI, there was high likelihood of persistent resistance to ampicillin (84.9%), amoxicillin-clavulanate (54.5%), ciprofloxacin (83.8%), and trimethoprim (78.3%). 3 However, nitrofurantoin showed only 20.2% persistent resistance at 3 months and 5.7% at 9 months, with only 2.6% prevalence of resistance with initial infection. 3

Beta-lactam antibiotics are not considered first-line therapy because of collateral damage effects and their propensity to promote more rapid recurrence of UTI. 3