Oral Antibiotics for Uncomplicated UTIs
For uncomplicated cystitis, use nitrofurantoin 100 mg twice daily for 5 days, fosfomycin 3 g single dose, or trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days (only if local resistance <20%) as first-line therapy. 1, 2
First-Line Agents for Uncomplicated Cystitis
The choice of first-line antibiotics prioritizes efficacy while minimizing collateral damage (selection of resistant organisms):
- Nitrofurantoin 100 mg twice daily for 5 days is recommended as first-line therapy 2
- Fosfomycin trometamol 3 g as a single dose is recommended as first-line therapy in women 2
- Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days should only be used if local resistance rates are below 20% 1, 2
These three agents are preferred because they achieve excellent urinary concentrations and cause minimal collateral damage compared to fluoroquinolones or broad-spectrum cephalosporins 1, 3.
Second-Line Agents
When first-line agents are contraindicated or ineffective:
- Oral cephalosporins (cephalexin, cefixime, cefpodoxime) can be used 1, 3
- Fluoroquinolones (ciprofloxacin, levofloxacin) should be reserved for cases where first-line agents fail or are contraindicated, due to increasing resistance and significant collateral damage 1, 3
- Amoxicillin-clavulanate is an alternative β-lactam option 1, 3
Treatment Duration
Treat for the shortest reasonable duration, generally no longer than 7 days 1:
- Nitrofurantoin: 5 days 2
- Trimethoprim-sulfamethoxazole: 3 days 2
- Fosfomycin: single dose 2
- Most other oral agents: 3-7 days 1
Single-dose regimens (except fosfomycin) show higher rates of bacteriological persistence and are not recommended 1.
Special Considerations for Pyelonephritis
For uncomplicated pyelonephritis requiring oral therapy:
- Ciprofloxacin 500-750 mg twice daily for 7 days (if fluoroquinolone resistance <10%) 1, 2
- Levofloxacin 750 mg once daily for 5 days 1
- Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 14 days 1
- Cefpodoxime 200 mg twice daily for 10 days 1
- Ceftibuten 400 mg once daily for 10 days 1
Critical caveat: When using oral cephalosporins for pyelonephritis, administer an initial intravenous dose of a long-acting parenteral antimicrobial (e.g., ceftriaxone) because oral cephalosporins achieve significantly lower blood concentrations than IV formulations 1.
Avoid nitrofurantoin, fosfomycin, and pivmecillinam for pyelonephritis as there are insufficient data regarding their efficacy in upper tract infections 1.
Key Clinical Pitfalls
- Do not use fluoroquinolones or trimethoprim-sulfamethoxazole if the patient received these antibiotics recently, as prior exposure significantly increases resistance risk 3, 4
- Check local antibiograms before prescribing empiric therapy, as resistance patterns vary geographically 1, 3
- Obtain urine culture before treatment in recurrent UTIs to guide appropriate therapy and document bacterial sensitivities 1, 2
- Do not treat asymptomatic bacteriuria except in pregnant women or before invasive urinary procedures 1
Men with UTI
For men with uncomplicated UTI, use trimethoprim-sulfamethoxazole 160/800 mg twice daily for 7 days (longer duration than women) 2.