What is the first-line antibiotic for an uncomplicated urinary tract infection (UTI) in a typical adult patient?

First-Line Antibiotic for Uncomplicated UTI

Nitrofurantoin 100 mg twice daily for 5 days is the preferred first-line antibiotic for uncomplicated urinary tract infections in adult women. 1

Primary First-Line Options

The following agents are recommended as first-line therapy for uncomplicated cystitis:

• Nitrofurantoin monohydrate/macrocrystals 100 mg twice daily for 5-7 days (preferred duration is 5 days) 1, 2
• Fosfomycin trometamol 3 g as a single dose (though slightly less effective than standard regimens) 1, 2
• Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days - ONLY if local E. coli resistance rates are below 20% 1, 2, 3

Why Nitrofurantoin is Preferred

Nitrofurantoin has emerged as the optimal first-line choice based on several critical factors:

• Minimal collateral damage: Produces less disruption to normal flora compared to fluoroquinolones and broad-spectrum agents, helping preserve broader-spectrum antibiotics for serious infections 1, 4
• Low resistance rates: Local E. coli resistance to nitrofurantoin typically remains below 10% 1
• Antimicrobial stewardship: The IDSA and AUA specifically recommend nitrofurantoin as first-line therapy to preserve fluoroquinolones for more serious infections 1
• Safety profile: The risk of serious pulmonary toxicity is only 0.001% and hepatic toxicity 0.0003% with short-term use 1

When NOT to Use Nitrofurantoin

Critical contraindications and limitations:

• Pyelonephritis or upper UTI: Nitrofurantoin does not achieve adequate tissue concentrations for kidney infections 1
• Creatinine clearance <60 mL/min: Consider alternative agents like trimethoprim-sulfamethoxazole or amoxicillin-clavulanate 1
• Infants under 4 months: Risk of hemolytic anemia 1
• Systemic symptoms: If fever, flank pain, or signs of pyelonephritis are present, use a fluoroquinolone instead 1

Trimethoprim-Sulfamethoxazole Considerations

TMP-SMX has been downgraded from universal first-line status:

• Resistance threshold: Only use if local E. coli resistance is documented to be <20% 1, 3
• Rising resistance: Increasing resistance rates have made TMP-SMX less reliable as empiric therapy, with studies showing higher treatment failure rates compared to nitrofurantoin 1
• Dosing: When appropriate, use 160/800 mg twice daily for 3 days 5, 2, 3

Fluoroquinolones: Reserve as Alternative Agents

Fluoroquinolones (ciprofloxacin, levofloxacin) should NOT be used as first-line therapy for uncomplicated cystitis:

• FDA safety warnings: Serious adverse effects involving tendons, muscles, joints, nerves, and central nervous system 1
• Collateral damage: Significant disruption to normal flora and promotion of multidrug-resistant organisms 1, 4
• Rising resistance: Local resistance rates now exceed 10% in many regions 1
• Reserve for serious infections: These agents should be preserved for pyelonephritis and complicated UTIs where they are truly needed 1, 3

β-Lactam Agents: Inferior Options

Amoxicillin-clavulanate and oral cephalosporins (cefdinir, cefaclor, cefpodoxime) are generally inferior:

• Lower efficacy: Less effective than first-line agents in clinical studies 1, 2
• More adverse effects: Higher rates of side effects compared to nitrofurantoin and TMP-SMX 1
• Use only when necessary: Reserve for situations where first-line agents cannot be used due to allergy, intolerance, or documented resistance 1

Special Populations

Men with Uncomplicated UTI

• Longer duration required: Treat for 7 days (not 5 days as in women) 3
• First-line options: Trimethoprim, trimethoprim-sulfamethoxazole, or nitrofurantoin for 7 days 3
• Always obtain culture: Urine culture and susceptibility testing should guide antibiotic selection 3
• Consider alternative diagnoses: Evaluate for urethritis and prostatitis, which may require different treatment 3

Women with Diabetes

• Treat similarly to non-diabetic women: Use the same first-line agents and durations if no voiding abnormalities are present 1, 2

Adults ≥65 Years

• Obtain culture: Urine culture with susceptibility testing is recommended to adjust therapy after initial empiric treatment 3
• Same first-line agents: Treatment durations do not differ from younger adults 3

Diagnostic Approach

For typical uncomplicated cystitis in women:

• No office visit or culture needed: Self-diagnosis with typical symptoms (frequency, urgency, dysuria, suprapubic pain) without vaginal discharge is sufficiently accurate 2, 3
• Start empiric therapy immediately: Delayed treatment is not recommended 2

When to obtain urine culture:

• Recurrent infections 3
• Treatment failure 3
• History of resistant organisms 3
• Atypical presentation 3
• All men with UTI symptoms 3
• Adults ≥65 years 3

Common Pitfalls to Avoid

• Do not treat asymptomatic bacteriuria: Treatment does not improve outcomes and promotes resistance (exceptions: pregnancy, pre-urologic procedures) 1
• Do not use amoxicillin or ampicillin alone: Poor efficacy and high resistance rates make these inappropriate for empiric therapy 1
• Do not exceed 7 days for acute cystitis: Longer durations increase adverse effects without improving outcomes 1
• Do not use nitrofurantoin for pyelonephritis: Inadequate tissue penetration makes it ineffective for upper UTIs 1