Oral Medications for Uncomplicated Urinary Tract Infections
First-Line Agents for Uncomplicated Cystitis
For uncomplicated cystitis in women, nitrofurantoin 100 mg twice daily for 5 days is the preferred first-line agent, followed by fosfomycin trometamol 3 g as a single dose, with trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days reserved only when local resistance rates are below 20%. 1
Recommended First-Line Options:
Nitrofurantoin 100 mg twice daily for 5 days - This agent demonstrates minimal collateral damage (selection of resistant organisms) and maintains excellent efficacy in real-world practice with lower treatment failure rates compared to other agents 1, 2
Fosfomycin trometamol 3 g single dose - Highly convenient single-dose therapy with maintained low resistance rates globally, though may have slightly inferior efficacy compared to multi-day regimens 3, 1, 4
Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days - Only use if local resistance rates are documented below 20%, as resistance has increased substantially in many communities 3, 1, 5
Why These Are Preferred:
The selection prioritizes agents with minimal "collateral damage" - meaning they don't promote selection of multi-drug resistant organisms or extended-spectrum beta-lactamase (ESBL) producing bacteria 1, 6. Nitrofurantoin shows superior outcomes with lower rates of both pyelonephritis (0.3% risk) and prescription switches (12.7%) compared to trimethoprim-sulfamethoxazole 2.
Second-Line and Alternative Agents for Cystitis
When first-line agents cannot be used due to allergy, intolerance, or documented resistance:
Fluoroquinolones (ciprofloxacin 250-500 mg twice daily for 3 days, or levofloxacin) - Highly efficacious but should be reserved for more serious infections due to significant collateral damage and FDA safety warnings 3, 1
Beta-lactams (amoxicillin-clavulanate, cefdinir, cefaclor, cefpodoxime-proxetil for 3-7 days) - Appropriate when other agents cannot be used, but have inferior efficacy and more adverse effects 3, 1
Pivmecillinam 400 mg twice daily for 3-7 days - Available in some European countries with minimal resistance, though may have inferior efficacy 3
Critical Pitfall to Avoid:
Never use amoxicillin or ampicillin alone for empirical treatment - these agents have very high resistance rates worldwide and poor efficacy 3.
Oral Treatment for Uncomplicated Pyelonephritis
For upper tract infections (pyelonephritis) in patients not requiring hospitalization:
First-Line Options:
Ciprofloxacin 500 mg twice daily for 7 days (or 1000 mg extended-release daily for 7 days) - Use only where fluoroquinolone resistance is below 10% 3, 1
Levofloxacin 750 mg once daily for 5 days - Alternative fluoroquinolone with once-daily dosing 3, 7
Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 14 days - Only if the organism is known to be susceptible 3, 1
Important Considerations for Pyelonephritis:
Always obtain urine culture before treatment to guide therapy if empirical treatment fails 3, 1
If fluoroquinolone resistance exceeds 10% locally, administer an initial intravenous dose of ceftriaxone 1 g or a consolidated 24-hour aminoglycoside dose before starting oral therapy 3, 1
Do not use nitrofurantoin, fosfomycin, or pivmecillinam for pyelonephritis - insufficient tissue penetration and data for upper tract infections 1
Oral Beta-Lactams for Pyelonephritis:
If beta-lactams must be used (less effective than fluoroquinolones):
Always give an initial IV dose of ceftriaxone 1 g when using oral cephalosporins for pyelonephritis 3, 1
Special Population: Men with UTI
All UTIs in men are considered complicated by definition and require longer treatment courses 8
Fluoroquinolones for 7-14 days - Use 7 days for straightforward cases, extend to 14 days when prostatitis cannot be excluded 8
Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 7 days for men with documented susceptibility 1
Critical Clinical Pitfalls to Avoid
Check local antibiograms before prescribing - resistance patterns vary significantly by geography and change over time 1, 6
Avoid fluoroquinolones for simple cystitis - reserve these for pyelonephritis and complicated infections to preserve their effectiveness and minimize serious adverse effects 3, 1
Don't treat asymptomatic bacteriuria except in pregnant women or before invasive urinary procedures 1, 5
Obtain cultures in recurrent UTIs before initiating treatment to document sensitivities and guide appropriate therapy 1
Recent antibiotic exposure increases resistance risk - if the patient received trimethoprim-sulfamethoxazole or fluoroquinolones recently, choose an alternative agent 3, 6