What is the first line treatment for an uncomplicated urinary tract infection (UTI)?

First-Line Treatment for Uncomplicated UTI

For uncomplicated urinary tract infections in women, use 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) as first-line therapy, with trimethoprim-sulfamethoxazole (160/800 mg twice daily for 3 days) reserved only if local E. coli resistance is documented below 20%. 1, 2

Recommended First-Line Agents in Women

The choice among first-line agents should be guided by your local antibiogram, but all three primary options demonstrate equivalent clinical efficacy while minimizing collateral damage (selection of resistant organisms): 1

• Nitrofurantoin: 100 mg twice daily for 5 days (macrocrystals, monohydrate, or prolonged-release formulations all acceptable) 1, 2, 3
• Fosfomycin trometamol: 3 g as a single dose (FDA-approved specifically for uncomplicated cystitis in women) 1, 2, 4
• Pivmecillinam: 400 mg three times daily for 3-5 days (where available) 1, 2

When to Use Trimethoprim-Sulfamethoxazole

Trimethoprim-sulfamethoxazole (160/800 mg twice daily for 3 days) can be used as first-line therapy only if your local E. coli resistance rate is documented to be less than 20%. 1, 5 This agent is no longer universally recommended as first-line due to increasing resistance rates in many communities. 6 If you lack local resistance data, assume resistance exceeds 20% and choose a different first-line agent. 1

Alternative Second-Line Options

When first-line agents cannot be used due to allergy, contraindication, or documented resistance, consider: 1, 2

• Cephalosporins (e.g., cefadroxil 500 mg twice daily for 3 days) if local E. coli resistance is <20% 1
• Fluoroquinolones (ciprofloxacin, levofloxacin) should be reserved for more invasive infections despite high efficacy, due to significant collateral damage including selection of multidrug-resistant organisms 1, 7, 5, 6

Treatment Duration

Keep antibiotic courses as short as reasonable: 1

• Most first-line agents: 3-5 days 1, 3
• Maximum duration for acute cystitis: 7 days 1
• Single-dose antibiotics show increased bacteriological persistence and should be avoided except for fosfomycin 1

Treatment in Men

Men with uncomplicated UTI require longer treatment duration and should always have urine culture with susceptibility testing: 3

• First-line options: Trimethoprim-sulfamethoxazole (160/800 mg twice daily), trimethoprim alone, or nitrofurantoin—all for 7 days 1, 3
• Consider urethritis and prostatitis as alternative diagnoses 3

When to Obtain Urine Culture

Diagnosis in women with typical symptoms (dysuria, frequency, urgency, suprapubic pain) without vaginal discharge can be made clinically without testing. 1, 3 However, obtain urine culture before treatment in these situations: 1, 2

• Suspected pyelonephritis 1
• Symptoms not resolving or recurring within 4 weeks after treatment 1
• Pregnant women 1
• Atypical presentation 1
• History of recurrent UTIs 3
• History of resistant organisms 3
• All men with UTI symptoms 3
• Adults ≥65 years old 3

Management of Treatment Failure

If symptoms do not resolve by end of treatment or recur within 2 weeks: 1, 2

• Obtain urine culture with susceptibility testing 1
• Assume the organism is not susceptible to the original agent 1
• Retreat with a 7-day regimen using a different antimicrobial class 1, 2

Non-Antimicrobial Option

For women with mild to moderate symptoms, symptomatic therapy with ibuprofen may be considered as an alternative to immediate antibiotics after shared decision-making, given the low risk of complications. 1, 2 However, immediate antimicrobial therapy remains the standard recommendation for most patients. 5

Critical Caveats

Pregnancy considerations: 1, 2

• Avoid trimethoprim in first trimester 1
• Avoid trimethoprim-sulfamethoxazole in last trimester 1

Agents to avoid: 5

• Amoxicillin or ampicillin should not be used for empirical treatment due to high resistance rates 5
• β-lactam agents (amoxicillin-clavulanate, cefpodoxime-proxetil) are less effective than first-line options 5

Do not treat asymptomatic bacteriuria except in pregnant women or before invasive urinary tract procedures. 1