What is the first-line antibiotic of choice for an uncomplicated urinary tract infection (UTI)?

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Last updated: December 9, 2025View editorial policy

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First-Line Antibiotic for Uncomplicated UTI

For uncomplicated urinary tract infections in women, nitrofurantoin (100 mg twice daily for 5 days) is the preferred first-line antibiotic, followed by fosfomycin (3g single dose) or pivmecillinam (400 mg three times daily for 3-5 days) where available. 1, 2

Recommended First-Line Options

The European Association of Urology and Infectious Diseases Society of America prioritize three agents based on minimal resistance patterns and preservation of broader-spectrum antibiotics for more serious infections:

  • Nitrofurantoin monohydrate/macrocrystals (100 mg twice daily for 5 days) is the most preferred option due to minimal resistance patterns and limited collateral damage to normal flora 2, 3

  • Fosfomycin trometamol (3g single dose) offers convenient single-dose therapy, though it may have slightly inferior efficacy compared to multi-day regimens 1, 2, 3

  • Pivmecillinam (400 mg three times daily for 3-5 days) is recommended primarily in European countries where it is available 1, 2

Alternative Options Based on Local Resistance

  • Trimethoprim-sulfamethoxazole (160/800 mg twice daily for 3 days) can be used only if local E. coli resistance rates are below 20% or if the specific isolate is known to be susceptible 1, 2, 4

  • Rising resistance rates globally have challenged trimethoprim-sulfamethoxazole's position as automatic first-line therapy, despite its historical use 1, 4

  • Trimethoprim alone (200 mg twice daily for 5 days) is an alternative, but should not be used in the first trimester of pregnancy 1

Antibiotics to Avoid for Empiric Treatment

  • Amoxicillin or ampicillin should never be used empirically due to poor efficacy and very high worldwide prevalence of antimicrobial resistance 1, 2

  • Fluoroquinolones (ciprofloxacin, levofloxacin) should be reserved for situations where first-line agents cannot be used, despite their high efficacy, to prevent promoting resistance to these important agents needed for more serious infections 2, 4

  • β-lactams (including amoxicillin-clavulanate, cefadroxil, cefdinir) generally have inferior efficacy and more adverse effects compared to other UTI antimicrobials 1, 2, 4

Special Population Considerations

Men with UTI

  • Male UTIs are considered complicated and require 7-14 days of treatment rather than the shorter courses used in women 1, 3
  • First-line options include trimethoprim-sulfamethoxazole (160/800 mg twice daily for 7-14 days) or fluoroquinolones (ciprofloxacin 500mg twice daily for 7 days) if local resistance is less than 10% 1, 3

Patients with Renal Impairment

  • For trimethoprim-sulfamethoxazole: standard dosing for CrCl >30 mL/min; reduce to half-dose for CrCl 15-30 mL/min; consider alternative agent for CrCl <15 mL/min 1

Common Pitfalls to Avoid

  • Do not prescribe trimethoprim-sulfamethoxazole empirically without knowledge of local resistance patterns - this is only appropriate when local resistance is documented to be <20% 2, 4

  • Do not use fluoroquinolones as first-line therapy despite their excellent efficacy, as this promotes resistance to agents needed for pyelonephritis and other serious infections 2

  • Do not use 3-day regimens in men - they require 7-14 days of therapy regardless of the antibiotic chosen 1, 3

  • Do not fail to obtain urine culture in cases of suspected pyelonephritis, symptoms that don't resolve within 4 weeks, atypical symptoms, pregnant women, or treatment failure 1, 2

When to Obtain Urine Culture

  • Urine culture is not routinely needed for straightforward uncomplicated cystitis in women 2, 3
  • Obtain culture for: recurrent infection, treatment failure, history of resistant isolates, atypical presentation, male patients, or symptoms that don't resolve by end of treatment or recur within 2 weeks 1, 2, 3

References

Guideline

Urinary Tract Infection Treatment Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

First-Line Antibiotics for E. coli Cystitis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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