First-Line Treatment for Uncomplicated UTI
Nitrofurantoin 100 mg twice daily for 5 days is the recommended first-line treatment for uncomplicated urinary tract infections in women, as it demonstrates superior clinical resolution rates compared to other first-line options. 1
Primary Treatment Recommendations
Nitrofurantoin is the preferred first-line agent based on current IDSA and AUA guidelines, with the following dosing: 1
- Nitrofurantoin 100 mg orally twice daily for 5 days 1
- This regimen achieves 70% clinical resolution at 28 days, significantly outperforming single-dose fosfomycin (58% resolution) 2
- Microbiologic cure rates are also superior with nitrofurantoin (74% vs 63% for fosfomycin) 2
Alternative First-Line Options
If nitrofurantoin cannot be used, consider these alternatives in order of preference:
Trimethoprim-sulfamethoxazole (TMP-SMX): 1, 3
- Dose: 160/800 mg (one double-strength tablet) twice daily for 3 days 1
- Critical caveat: Only use if local E. coli resistance rates are below 20% 1
- FDA-approved for uncomplicated UTI caused by susceptible E. coli, Klebsiella, Enterobacter, Morganella, and Proteus species 3
- Dose: 3 g single oral dose 1, 4
- Must be mixed with water before ingesting; never take in dry form 4
- May be taken with or without food 4
- Important limitation: Slightly inferior efficacy compared to nitrofurantoin, but offers convenience of single-dose therapy 1, 2
Trimethoprim alone: 1
- Dose: Not specified in guidelines but typically used for 3 days 1
- Consider when sulfa allergy precludes TMP-SMX use
Agents to Avoid or Reserve
Fluoroquinolones (ciprofloxacin, levofloxacin): 1
- Should be reserved as alternative agents only when first-line options cannot be used 1
- FDA has issued serious safety warnings regarding tendon, muscle, joint, nerve, and CNS adverse effects 1
- Increasing resistance rates and "collateral damage" to normal flora make them less desirable 1
Beta-lactams (amoxicillin-clavulanate, cefdinir, cefaclor, cefpodoxime): 1
- Generally have inferior efficacy and more adverse effects compared to first-line agents 1
- Use only when first-line agents cannot be used 1
- Treatment duration: 3-7 days 1
Amoxicillin or ampicillin alone: 1
- Should NOT be used for empirical treatment due to poor efficacy and high resistance rates 1
Important Clinical Considerations
- Urine culture is NOT necessary before starting empiric therapy in straightforward uncomplicated UTI 1
- Self-diagnosis with typical symptoms (frequency, urgency, dysuria, suprapubic pain) without vaginal discharge is sufficiently accurate in women 5
- Reserve urine culture for: recurrent infections, treatment failure, history of resistant organisms, or atypical presentation 5
Treatment duration matters: 1
- The 5-day nitrofurantoin course balances efficacy with minimizing adverse effects 1
- Shorter courses may lead to treatment failure 2
Contraindications to nitrofurantoin: 1
- Infants under 4 months (risk of hemolytic anemia) 1
- Upper UTIs or pyelonephritis (inadequate tissue concentrations) 1
- Any degree of renal impairment 6
- Last trimester of pregnancy 6
Safety Profile
Nitrofurantoin adverse events are primarily gastrointestinal and occur infrequently: 2
- Nausea: 3% of patients 2
- Diarrhea: 1% of patients 2
- Serious side effects (pulmonary reactions, polyneuropathy) mainly occur with long-term use, not short-term therapy 6
Special Populations
Men with uncomplicated UTI: 1, 5
- Always obtain urine culture and susceptibility testing 5
- First-line options: TMP-SMX, trimethoprim, or nitrofurantoin for 7 days (longer than women) 5
- Consider urethritis and prostatitis in differential diagnosis 5
Older adults (≥65 years): 5
- Obtain urine culture with susceptibility testing 5
- Same first-line antibiotics and durations as younger adults in nonfrail patients without relevant comorbidities 5
Resistant organisms: 7
- VRE-caused uncomplicated UTI: Nitrofurantoin 100 mg every 6 hours, fosfomycin 3 g single dose, or high-dose ampicillin 7