First-Line Therapy for Uncomplicated Urinary Tract Infections
For acute uncomplicated cystitis in women, nitrofurantoin (100 mg twice daily for 5 days), fosfomycin trometamol (3 g single dose), or pivmecillinam (400 mg three times daily for 3-5 days) are the recommended first-line agents, with trimethoprim-sulfamethoxazole reserved only when local E. coli resistance is documented below 20%. 1
Primary First-Line Agents
The following three agents should be prioritized based on their efficacy, minimal collateral damage (selection of resistant organisms), and favorable resistance profiles:
Nitrofurantoin: 100 mg twice daily for 5 days is highly effective with only 2.6% baseline resistance and minimal persistent resistance (5.7% at 9 months) 2, 1
Fosfomycin trometamol: 3 g as a single oral dose provides excellent convenience and equivalent efficacy to multi-day regimens 1, 3
Pivmecillinam: 400 mg three times daily for 3-5 days (available in Europe but not North America) demonstrates minimal collateral damage 2, 1
When Trimethoprim-Sulfamethoxazole Can Be Used
Trimethoprim-sulfamethoxazole (160/800 mg twice daily for 3 days) should only be used as first-line therapy if your local antibiogram documents E. coli resistance rates below 20%. 1 This agent was historically the traditional first-line choice but rising resistance rates (78.3% persistent resistance in some cohorts) have necessitated its demotion to conditional use only 2.
Agents to Avoid as First-Line Therapy
Fluoroquinolones (ciprofloxacin, levofloxacin, norfloxacin) should be reserved for more invasive infections like pyelonephritis due to significant collateral damage and FDA warnings against their use for uncomplicated UTIs given unfavorable risk-benefit ratios 2, 1
Beta-lactams (amoxicillin-clavulanate, cephalexin, cefdinir) have inferior efficacy, promote more rapid UTI recurrence, and cause greater collateral damage compared to first-line agents 2
Amoxicillin or ampicillin alone should never be used empirically due to very high worldwide resistance rates (84.9% in some studies) and poor efficacy 2
Treatment Duration
Keep antibiotic courses as short as clinically reasonable: 1
- Nitrofurantoin: 5 days
- Fosfomycin: Single dose
- Pivmecillinam: 3-5 days
- Trimethoprim-sulfamethoxazole (when appropriate): 3 days
- Maximum duration for any acute cystitis regimen: 7 days 1
Management of Treatment Failure
If symptoms persist at the end of treatment or recur within 2 weeks: 1
- Obtain urine culture with susceptibility testing
- Assume the organism is not susceptible to the original agent
- Retreat with a 7-day regimen using a different antimicrobial class 1
Critical Caveats
Do not treat asymptomatic bacteriuria except in pregnant women or before invasive urinary tract procedures, as treatment increases the risk of symptomatic infection, bacterial resistance, and healthcare costs 2, 1
In pregnancy, avoid trimethoprim in the first trimester and trimethoprim-sulfamethoxazole in the last trimester 1
For recurrent UTIs, the same short-duration first-line agents should be used—there is no evidence that longer courses or more potent antibiotics are needed, and such approaches may actually increase recurrence rates by disrupting protective periurethral and vaginal microbiota 2
Alternative Non-Antimicrobial Option
For women with mild to moderate symptoms who prefer to avoid immediate antibiotics, symptomatic therapy with ibuprofen may be considered after shared decision-making, given the low risk of complications in uncomplicated cystitis 1