Treatment of Urinary Tract Infections
First-Line Treatment for Uncomplicated Cystitis
For uncomplicated cystitis in women, nitrofurantoin (100 mg twice daily for 5 days) is the preferred first-line agent, with trimethoprim-sulfamethoxazole (160/800 mg twice daily for 3 days) and fosfomycin (3 g single dose) as equally acceptable alternatives. 1, 2
Specific First-Line Regimens:
- Nitrofurantoin: 100 mg twice daily for 5 days 1, 2
- Fosfomycin trometamol: 3 g single dose 1, 2
- Trimethoprim-sulfamethoxazole (TMP-SMX): 160/800 mg twice daily for 3 days—only if local resistance rates are <20% 1, 2
- Trimethoprim alone: 100 mg for 3 days 1, 3
Rationale for First-Line Choices:
Nitrofurantoin is prioritized because it achieves excellent urinary concentrations, maintains low resistance rates (resistance decays quickly even when present), and spares more systemically active agents for other infections 1, 4. The 2016 FDA advisory specifically warns against fluoroquinolones for uncomplicated UTIs due to serious adverse effects including tendon, muscle, joint, nerve, and central nervous system damage that create an unfavorable risk-benefit ratio 1, 5.
Critical Pitfalls to Avoid:
- Never use fluoroquinolones as first-line therapy for uncomplicated cystitis due to resistance patterns, collateral damage to microbiota, and serious adverse effects 1, 2
- Do not use nitrofurantoin for pyelonephritis or febrile UTIs—it does not achieve adequate tissue concentrations 2
- Avoid amoxicillin alone—global surveillance shows 75% median resistance in E. coli (range 45-100%) 1
- Never treat asymptomatic bacteriuria except in pregnant women or patients scheduled for urologic procedures, as this fosters antimicrobial resistance and increases recurrence 1, 2
Treatment for Acute Pyelonephritis
For mild-to-moderate pyelonephritis, ciprofloxacin or TMP-SMX are first-line oral options if local resistance rates permit (<10% for pyelonephritis), while ceftriaxone is the preferred intravenous agent for patients requiring parenteral therapy. 1
Specific Regimens:
- Oral therapy: Ciprofloxacin or TMP-SMX (only if local resistance <10%) 1
- Intravenous therapy: Ceftriaxone (first-generation cephalosporins also reasonable) 1
- Duration: 5-7 days for fluoroquinolones, 7 days for β-lactams 1
When to Use Broader Spectrum Agents:
Use agents with antipseudomonal activity only in patients with risk factors for nosocomial pathogens, such as recent hospitalization, catheterization, or known multidrug-resistant organisms 1, 4.
Treatment for Men with UTIs
Men with UTIs require longer treatment duration (7 days) and should always receive antibiotics with urine culture guidance. 2, 3
Specific Regimens for Men:
- TMP-SMX: 160/800 mg twice daily for 7 days (preferred) 2
- Trimethoprim: 100 mg for 7 days 3
- Nitrofurantoin: For 7 days 3
Important Considerations:
Always consider urethritis and prostatitis in men presenting with UTI symptoms, as these require different management approaches 3. Obtain urine culture and susceptibility testing before initiating treatment 3.
Treatment Algorithm Based on Local Resistance Patterns
Step 1: Assess Local Antibiogram
- If TMP-SMX resistance <20%: TMP-SMX is acceptable 1, 2
- If fluoroquinolone resistance <10%: Consider for pyelonephritis only 1
- If resistance exceeds these thresholds: Use nitrofurantoin or fosfomycin 1, 2
Step 2: Consider Patient-Specific Factors
- Prior culture data: Use previous susceptibility results to guide empiric choice 1
- Recent antibiotic exposure: Avoid recently used agents due to higher resistance risk 4
- Drug allergies and side effects: Document and avoid 1
- Pregnancy status: Use cephalosporins (e.g., cefuroxime) or nitrofurantoin 6
Step 3: Obtain Culture When Indicated
Obtain urine culture before treatment in: 2
- Suspected pyelonephritis
- Symptoms persisting >4 weeks after treatment
- Recurrent UTIs
- Pregnant women
- Men with UTI symptoms
- Atypical presentations
Management of Recurrent UTIs
For recurrent UTIs (≥2 infections in 6 months or ≥3 in one year), implement a stepwise approach prioritizing non-antibiotic alternatives before prophylactic antibiotics. 1
Postmenopausal Women:
- First-line: Vaginal estrogen with or without lactobacillus-containing probiotics 1
- Alternative: Methenamine hippurate and/or lactobacillus probiotics 1
- Last resort: Daily antibiotic prophylaxis (nitrofurantoin 50 mg, TMP-SMX 40/200 mg, or trimethoprim 100 mg) 1
Premenopausal Women with Post-Coital Infections:
- First-line: Low-dose antibiotic within 2 hours of sexual activity for 6-12 months 1
- Alternative: Methenamine hippurate and/or lactobacillus probiotics 1
Premenopausal Women with Non-Coital Infections:
- First-line: Behavioral and lifestyle modifications 1
- Second-line: Daily antibiotic prophylaxis 1
- Alternative: Methenamine hippurate and/or lactobacillus probiotics 1
Evidence for Non-Antibiotic Alternatives:
Daily antibiotic prophylaxis is more effective than non-antibiotic alternatives (reducing UTI rate to 0.4/year with estrogen plus acupuncture), but the quality of evidence is critically low 1. The oral immunostimulant OM-89 (Uro-Vaxom) shows safety and efficacy in reducing recurrence for 6-12 months in meta-analyses of RCTs 1, 6.
Special Considerations for Antibiotic Stewardship
Avoid Classification Errors:
Do not classify patients with recurrent UTIs as "complicated" unless they have structural/functional urinary tract abnormalities, immunosuppression, or pregnancy—this leads to unnecessary broad-spectrum antibiotic use 1.
Treatment Failure Management:
If symptoms persist despite treatment, repeat urine culture to assess for ongoing bacteriuria before prescribing additional antibiotics 1. Use nitrofurantoin for re-treatment when possible since resistance is low and decays quickly 1.
Duration Principles:
Treatment should be as short as reasonable while ensuring symptom resolution 2. Longer courses or more potent antibiotics are not needed for recurrent UTIs and may increase recurrence by disrupting protective periurethral and vaginal microbiota 1.